Term
Which of the following histones is not in the nucleosome core?
a. H1
b. H2A
c. H2B
d. H4 |
|
Definition
| A- H1 links nucleosome beads together in a string, each of which consists of an octamer composed of lysine and arginine AAs |
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|
Term
| Why is methylation of cytosine and adenine critical during DNA replication? |
|
Definition
| Methylation of these residues on the template strand allows mismatch repair enzymes to distinguish between new and old strands |
|
|
Term
True or False:
Acetylation of histone proteins leads to increased transcription of genes within the DNA wrapped around that nucleosome. |
|
Definition
| True- Acetylation by Histone acetylases relaxes DNA, allowing transcription to occur and DNA to be sterically accessed |
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|
Term
| Why does increasing the G-C content increase the melting temperature of DNA? |
|
Definition
| This Purine (G- 2 rings)/Pyrimidine (C- 1 ring)combination as 3 hydrogen bonds, vs. 2 for A/T, so there it takes more temperature to denature. |
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|
Term
Match each of the following molecular characteristic with its appropriate nucleic acid (ATGC)
1) Methyl group
2) Ketone
3) Deaminates to Uracil |
|
Definition
PURe As Gold (A, G Purines)
CUT the Py (C, T, U Pyrimidines)
1) Thymine
2) Guanine
3) Cytosine
** CpG islands are mutational hotspots because Cytosine can spontaneously deaminate to U. |
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|
Term
Which amino acid is not required for purine synthesis?
1)Lysine
2)Glycine
3)Aspartate
4)Glutamine |
|
Definition
| 1- GAG are required to make A/G! |
|
|
Term
| What is the difference between a nucleotide and a nucleoside? |
|
Definition
Nucleotides are Nucleosides with Phosphate groups (Ribose + Base)
NuclseoSide= base + ribose (Sugar)
NucleoTide= base + ribose + phosphaTe |
|
|
Term
| How are Purines and Pyrimidines synthesized, de novo, respectively? |
|
Definition
Ribonucleotides are made first and are converted to Deoxyribonucleotides by Ribonucleotide reductase.
1) Purine (A/G)
- start with sugar + phosphate (PRPP)
- Add base
2) Pyrimidine (C/T/U)
- Make temporary base (orotic acid)
- Add sugar + phosphate (PRPP)
- Modify base |
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|
Term
Which of the following compounds does not act by interfering with nucleotide synthesis?
a. Hydroxyurea
b. 6-mercaptopurine
c. 5-flourouracil
d. Metronidazole
e. Methotrexate
f. Trimethoprim |
|
Definition
D- antibiotic forms unstable interaction with DNA
The other antineoplastic and antibiotic drugs do
a. Hydroxyurea- inhibits ribonucleotide reductase
b. 6-MP- blocks de novo purine synthesis
c. 5-FU- inhibits thymidylate synthase (decreasing dTMP/thymine)
e. Methotrexate- inhibits dihydrofolate reductase (decreasing dTMP)
f. Trimethoprim- inhibits bacterial dihydrofolate reductase (decreasing dTMP) |
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|
Term
A patient presents with high urinary orotic acid, megaloblastic anemia and failure to thrive.
There is no evidence of hyperammonemia.
How do you treat? |
|
Definition
This is Orotic Aciduria (Autosomal Recessive), where patients cannot convert orotic acid to UMP (de novo pyrimidine synthesis) due to defect in either orotic acid phosphoribosyltransferase or orotidine 5'phosphate decarboxylase.
Treat with Oral Uridine
- Urinary orotic acid is common to Orotic aciduria and OTC deficiency, but in OTC deficiency, you see hyperammonemia as well.
- The megaloblastic anemia (does not respond to vitamin B12 or folic acid) is consistent, as is failure to thrive |
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|
Term
A patient presents with high urinary orotic acid, a megaloblastic anemia, failure to thrive and hyperammonemia.
How do you treat? |
|
Definition
This is OTC deficiency (hyperammonemia rules out Orotic Aciduria).
1) Low-Nitrogen Diet
2) Nitrogen scavengers; sodium benzoate and sodium phenylbutyrate
3) Supplemental AAs |
|
|
Term
A young patient's blood work comes back and you discover an unusually high level of ATP and dATP.
Why might you worry about SCID developing in this case? |
|
Definition
Excess ATP/dATP suggets an Adenosine Deaminase Deficiency, an AR metabolic disorder where the enzyme that normally converts adenosine to inosine in the Purine salvage pathway towards uric acid production, is deficient.
Excess ATP/dATP imbalances the nucleotide pool via feedback inhibition of ribonucleotide reductase, thereby preventing DNA synthesis and decreasing the lymphocyte count.
SCID happens to kids (e.g. "bubble boy") and was the 1st disease to be treated with experimental gene therapy. |
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|
Term
A patient presents with mental retardation, aggressive behavior, hyperuricemia, gout and choreoathetosis (writhing, chorea-like movements).
You also notice evidence of self-mutilation.
What is the biochemical basis of this disease? |
|
Definition
Lesch-Nyhan syndrome (Purine salvage deficiency)
**He's Got Purine Recovery Trouble (HGPRT)**
X-linked recessive condition where HGPRT is absent, so Hypoxanthine cannot be converted to IMP and Guanine cannot be converted to GMP. As a result, too much uric acid production and de novo purine synthesis occurs. |
|
|
Term
| What are the 2 major purine salvage deficiencies? |
|
Definition
1) Adenosine Deaminase Deficiency
- dATP buildup leads to inhibition of ribonucleotide reductase, decreasing DNA synthesis and lowering lymphocyte count (THINK SCID)
2) Lesch-Nyhan syndrome
- X-linked
- He's Got Purine Recovery Trouble (HGPRT absence)
- Guanine and Hypoxanthine build up leading to excess Uric Acid and de novo purine synthesis
- End up with Gout, Retardation, Aggression, hyperuricemia and Choreoathetosis |
|
|
Term
What do each of the following features of the Genetic Code mean?
1. Unambiguous
2. Degenerate
3. Commaless, non-overlapping
4. Universal |
|
Definition
1. Each codon specifies only 1 amino acid
2. More than 1 codon per AA (EXCEPT, M and Y, which are AUG and UGG, respectively)
3. Read from a fixed starting point as a continuous sequence of bases (EXCEPT some viruses)
4. Genetic code is conserved throughout evolution |
|
|
Term
Describe each of the following mutation types in DNA.
1. Silent
2. Missense
3. Nonsense
4. Frame shift |
|
Definition
Nonsense> Missense> Silent (order of damage)
1. Same AA, (tRNA wobble in 3rd base)
2. Changed AA, but it is similar in chemical structure
3. Change resulting in EARLY STOP (STOP the nonsense)
4. Change in misreading all nucleotides downstream, resulting in truncated, nonfunctional protein. |
|
|
Term
What is the role of each of the following in DNA replication?
1. ssDNA-binding proteins
2. Topoisomerase
3. Primase
4. Polymerase III
5. Polymerase I
6. Ligase
7. Telomerase |
|
Definition
1. Prevent re-annealing
2. Nick and relieve supercoil (target of Flouroquinolones)
3. RNA primer for DNA Poli III
4. Prokaryote ONLY, with exonuclease proof-reading
5. Prokaryote ONLY. Degrades RNA primer (5'-3' exonuclease) and gap-filling with DNA
**also can to addition like Poli III
6. Seals
7. Adds DNA to 3' end of chromosomes to avoid loss of material with every duplication. |
|
|
Term
| What are the 3 major types of ssDNA repair? |
|
Definition
1. Nucleotide Excision Repair (NER)- Xeroderma Pigmentosa
- Endonucleases cut out damaged Oligo-containing base
- DNA Poli fills in and Ligase reseals
2. Base Excision Repair (BER)- Spontaneous/toxic deamination repair
- Glycosylases recognize and remove damaged base
- AP endonuclease cuts DNA at apyrimidinic/apurinic sites
- Empty sugar removed
- Poli and Ligase fill and re-seal
3) Mismatch Repair- HNPCC
- Unmethylated, newly synthesized string is recognized
- Mismacthed nucleotides are removed
- Gap filled and resealed |
|
|
Term
| What do Xeroderma Pigmentosum and Hereditary nonpolyposis colorectal cancer (HNPCC) have in common? |
|
Definition
ssDNA repair issues
1) XD (AR) involves mutated enzymes important for Nucleotide Excision Repair, preventing pyrimidine dimer repair due to UV light (GET OUT OF SUN)
2) HNPCC (AD)involves mutated Mismatch repair enzymes |
|
|
Term
| How does repair of dsDNA breaks occur and what does it have to do with ataxia and small, dilated blood vessels in children? |
|
Definition
Non-homologous end joining, where 2 ends of DNA fragments are brought together, regardless of homology
- Rare, inherited mutations in ATM gene, which is critical for NHEJ, results in Ataxia Telangiectasia (Louis-Barre syndrome) |
|
|
Term
| What is the directionality of DNA, RNA and protein synthesis? |
|
Definition
1) DNA/RNA are 5'-3'
2) mRNA is read 5'-3' and protein is synthesized N-C. |
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|
Term
| Why are some drugs that affect DNA synthesis called "chain terminators"? |
|
Definition
They block replication by modifying the 3'OH, which prevents addition of next nucleotide.
The 3'OH of the existing strand must attack the high-energy phosphate bond on the added 5' end of the nucleotide in order to continue chain growth
**Remember, the 5' triphosphate is the target of 3'-OH attack** |
|
|
Term
| What distinguishes the three types of RNA? |
|
Definition
Rampant, Massive, Tiny
1) rRNA is most abundant
2) mRNA is longest
3) tRNA is smallest |
|
|
Term
| How is the role of the AUG codon different in Eukaryotes and Prokaryotes? |
|
Definition
1) Start codon (Methionine) for P-synthesis in Eukaryotes
2) f-Met is Prokaryotes
**UAG, UAA, UGA are stop codons** |
|
|
Term
Which of the following is NOT a stop codon?
1. UGG
2. UGA
3. UAG
4. UAA |
|
Definition
1- UGG
U Go Away, U Are Away and U Are Gone |
|
|
Term
| Which RNA Polymerases make rRNA, mRNA and tRNA in eukaryotes? |
|
Definition
RNA Poli 1 makes all 3 in Prokaryotes
In Eukaryotes, they are numbered as their products are used during P-synthesis!
**no proofreading**
1) RNA Poli 1 makes rRNA
2) RNA Poli 2 makes mRNA- opens DNA at promotor site (initiate chains)
3) RNA Poli 3 makes tRNA |
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|
Term
A patient presents with liver failure and admits to cooking with a new kind of mushroom he found in his yard.
What happened? |
|
Definition
Alpha-amanitin (death cap mushrooms) inhibits RNA Polymerase II, preventing mRNA production and protein synthesis.
Lack of protein causes liver failure. |
|
|
Term
| Describe the major steps of RNA processing in eukaryotes. Which occur in the nucleus/cytosol? |
|
Definition
1) Initial transcript (heterogenous nuclear RNA) undergoes 5' capping with 7-methylgunaosine (N)
2) Polyadenylation on 3' end (200 As) (N)
3) Splicing of introns (N)
4) Capped, tailed, spliced mRNA is sent to cytoplasm. |
|
|
Term
True or False:
Poly-A Polymerase does not require a template for poly-A addition in the nucleus |
|
Definition
True
The signal is AAUAAA, and then it goes! |
|
|
Term
| How does splicing of pre-mRNA occur? |
|
Definition
** Patients with Lupus make antibodies to snRNPs!**
1. Primary transcript combines with snRNPs and other proteins to form spliceosome
2. Lariat-shaped intermediate generated
3. Lariat released to remove intron precisely and join 2 exons (mRNA) |
|
|
Term
| How does the addition of Lactose and Glucose to E. coli alter the behavior of the Lac operon, respectively? |
|
Definition
When activated, the lac operon enables lactose metabolism
Lactose= inhibit repressor on operator
Glucose= lower cAMP and prevent CAP binding
1) Lactose inhibits Repressor protein, which normally binds to operator, blocking promotor activation
2) Glucose inhibits cAMP production, which normally stimulates the Catabolite activator protein (CAP) to bind to the operon and assist RNA-poly binding to the adjacent promotor |
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|
Term
| What is the basic structure/charging of a tRNA molecule? |
|
Definition
1) 75-90 nucleotides with CCA (Can Carry AAs) at 3' end and a high percentage of chemically modified bases
- Aminoacyl-tRNA synthetase (1 per AA) uses ATP and adds AA to CCA (checks AA before and after addition,and hydrolyzes if incorrect)
**Tetracyclines binds 30S subunit and prevent attachment of aminoacyl tRNA**
2) Initiation Factor-2-mediated presentation of anticodon to match appropriate mRNA. |
|
|
Term
|
Definition
| Accuring base pairing is only required by the first 2 nucleotide positions of an mRNA codon to a tRNA, so the 3rd position may "wobble" due to degeneracy. |
|
|
Term
| What are the 3 major steps of Protein Synthesis? |
|
Definition
1) Initiation
- Activated by GTP hydrolysis
- Initiation factors (eIFs) assemble 40S ribosomal subunit with initiator tRNA and are released when mRNA and ribosomal subunit assemble with complex
2) Elongation
- Aminoacyl-tRNA binds to A site (except for initiator M)
- Ribosomal rRNA catalyzes peptide bond formation and transfers growing polypeptitde to Amino Acid in A site.
- Ribosome advances 3 nucleotides toward 3' end of RNA, moving peptidyl RNA to P site (translocation)
3) Termination
- Stop codon is recognized by release factor and completed protein is released from ribosome |
|
|
Term
| What occurs in the "A," "P" and "E" sites of the ribosome complex? |
|
Definition
APE
1) A= incoming Aminoacyl-tRNA
2) P= growing Peptide
3) E= holds Empty tRNA as it Exits |
|
|
Term
| Which antibiotics act on protein synthesis? |
|
Definition
1) Aminoglycosides bind 30s and inhibit formation of initiation complex and cause misreading of mRNA
2) Macrolides bind 50S subunit and prevent release of uncharged tRNA from E site
3) Chloramphenicol inhibits 50S peptidyltransferase
- block peptide bond formation** |
|
|
Term
| What are the 3 types of post-translational modifications? |
|
Definition
1) Trimming- N or C-terminal removal to activate zymogen
2) Covalent alteration (phosphate, hydroxyl, glycosyl)
3) Proteosomal degradation (ubiquitination of defective proteins) |
|
|
Term
| What is the role of Cyclins and CDKs? |
|
Definition
| Cyclins are cell-phase specific, regulatory proteins, which activate cyclin-dependent kinases, which together form complexes that control cell cycle events. |
|
|
Term
| What is the unique role played by P53 and Rb? |
|
Definition
| Tumor Suppressor proteins that inhibit G1-S transitions, and prevent unrestrained growth (mutations cause cancer) |
|
|
Term
| Which cells types are Permanent vs. Stable (quiescent) vs. Labile? |
|
Definition
1) Neurons, skeletal and cardiac muscle cells and RBCs are permanent, and remain in G0. Replenished by stem cells only
2) Hepatocytes and Lymphocytes are Stable, but can be induced from G0 into G1
3) Hair follicle, skin, bone marrow and gut epithelial cells never go into Go, but divide rapidly with short G1. |
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|
Term
| Why is it significant that both goblet cells of the small intestine and Ab-secreting plasma cells are rich in RER? |
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Definition
RER ("Nissl bodies" in neurons) is important for synthesis of secretory proteins and N-linked oligosaccharide addition
**Free ribosomes are site of cytosolic and organellar protein synthesis** |
|
|
Term
| Why are hepatocytes and certain adrenal cortex cells rich in Smooth ER? |
|
Definition
| Hepatocytes, as well as steroid hormone-producing cells of Adrenal Cortex need SER to make steroids and detoxify drugs and poisons. |
|
|
Term
| What happens to proteins that leave the ER and reach the Golgi apparatus? |
|
Definition
Golgi
1) MODIFIES N-oligosarcharides on asparagine
2) ADDS O-oligosaccharides on threonine and serine
3) ADDS mannose-6-phosphate to proteins for trafficking to lysosomes (in endosomes) |
|
|
Term
Which of the following is NOT a vesicular trafficking protein?
a. COPI
b. COPII
c. CFTR
d. Clathrin |
|
Definition
C- CFTR is a chloride channel that is mutated in Cystic Fibrosis (at Phe 508)
a. COPI is for retrograde trafficking (Golgi...ER)
b. COPII is for anterograde trafficking (RER...cis-Golgi)
d. Clathrin: trans-Golgi...lysosomes, plasma membrane...endosomes (receptor-mediated endocytosis) |
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|
Term
A patient presents with coarse facial features, clouded corneas, restricted joint movement and high plasma lysosomal enzymes.
What is the basis of this disease? |
|
Definition
Inclusion Cell Disease (I-cell disease), which involves a failure to add mannose-6-phosphate to proteins in the golgi apparatus.
Because these proteins are not sent to the lysosome, they are secreted out of the cell instead
**can be fatal in children** |
|
|
Term
| What is metabolized in the Peroxisome? |
|
Definition
Membrane-enclosed organelle
1) catabolism of very long FAs and AAs |
|
|
Term
| What is the molecular function of Dynein and Kinesin? |
|
Definition
Molecular motor proteins that transport cargo toward opposite ends of microtubule tracks
1) Dynein= retrograde (+ to -)
2) Kinesin= anterograde (- to +) |
|
|
Term
| Which cellular structures are composed of microtubues? |
|
Definition
Cylindrical structures composed to helical arrays of alpha and beta tubulin (2 GTP bound to each dimer).
1) Cilia
2) Mitotic spindles
3) Flagella |
|
|
Term
A patient presents with partial albinism, recurrent pyogeninc infections and peripheral neuropathy.
What is the molecular basis of this disease? |
|
Definition
| This triad (albinism, neuopathy and pyogenic infections) suggests Chediak-Higashi syndrome, which involves a defect in microtubule polymerization, inhibiting phagosome/lysosome fusion. |
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|
Term
A patient presents with partial albinism, recurrent pyogeninc infections and peripheral neuropathy.
What is the molecular basis of this disease? |
|
Definition
| This triad (albinism, neuopathy and pyogenic infections) suggests Chediak-Higashi syndrome, which involves a defect in microtubule polymerization, inhibiting phagosome/lysosome fusion. |
|
|
Term
Which of the following drugs does NOT target microtubules?
1. Mebendazole
2. Vincristine/vinblastine
3. Cochicine
4. Paclitaxel
5. Sulfamethoxazole
6. Griseofulvin |
|
Definition
5. Sulfamethoxazole (Bactrim) is an antibiotic and is the drug of choice for Pneumocystis. It is a competitive antagonist of folic acid, used in bacterial DNA synthesis.
1. Mebendazole (anti-helminthic, especially nematodes)
2. Vincristine/vinblastine (anti-cancer, disrupts polyermatization)
3. Cochicine (anti-gout, prevents polymerization)
4. Paclitaxel (anti-breast cancer, prevents de-polymeraization)
6. Griseofulvin (anti-fungal-dermatophytes by binding keratin) |
|
|
Term
What is the molecular basis of the condition that causes male and female infertility, bronchiectasis and recurrent sinusitis.
This same condition is associated with situs inversus |
|
Definition
Kartagener's syndrome- Associated with Situs inversus
- Axonemal Dynein (links 9 peripheral microtubule doublets in cilia) defect prevents cilium bending and prevents sperm motility as well as preventing cilia in sinuses from pushing out bacteria and particles. |
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|
Term
Which of the following does NOT involve Actin and Myosin?
1. Microvili
2. Cilia
3. Muscle contraction
4. Cytokinesis
5. Adherens junctions |
|
Definition
2. Cilia are composed of microtubules!
Actin and Myosin are in microvili, muscle contraction, cytokinesis and adherens junctions |
|
|
Term
Which of the following does NOT involve microtubules?
1. Flagella
2. Cilia
3. Mitotic Spindle
4. Cytokinesis
5. Centrioles |
|
Definition
4. Actin and Myosin are critical for cytokinesis
Centrioles, Flagella, Cilia, Mitotic spindle AND axonal transport ALL involve microtubules |
|
|
Term
Which of the following does NOT involve Intermediate filaments?
1. Vimentin
2. Cytokeratin
3. Desmin
4. Lamins
5 Adherens junctions
6. GFAP |
|
Definition
5. Adherens junctions involve actin/myosin- they connect adjacent epithelial cells together by their actin filaments internally
Vimentin (connective tissue), Desmin (muscle), Cytokeratin (epithelial), Lamins and GFAP (neuroglia) all are examples of IFs |
|
|
Term
Which of the following is not a major component of cell plasma membranes?
a. Cholesterol
b. Phospholipid
c. Lamins
d. Protein
e. Sphingolipid |
|
Definition
C. Nuclear lamins are intermediate filaments that interact with membrane-associated proteins to form the nuclear lamina on the interior of the nuclear envelope
The plasma membrane is composed of Cholesterol (50%), Phospholipid (50%), Glycolipid, Sphingolipid and Protein. |
|
|
Term
| What is the importance of the high cholesterol or long saturated FA content in the plasma membrane? |
|
Definition
Raises melting temperature and Decreases fluidity.
Changes is membrane fluidity affect endocytosis and intracellular signalling |
|
|
Term
What are each of the following IHC stains used for?
a. Vimentin
b. Desmin
c. Cytokeratin
d. GFAP
e. Neurofilaments |
|
Definition
a. Connective tissue
b. Muscle
c. Epithelial cells
d. Neuroglia
e. Neurons |
|
|
Term
| What is common about Ouabain and Cardiac glycosides? How do they differ? |
|
Definition
Quabain and Cardiac glycosides both inhibit the Na/K pump.
Ouabain inhibits the pump by binding to the K+ site (preventing potassium influx)
Cardiac Glycosides such as Digoxin and Digitoxin directly inhibit the ATPase,leading to indirect inhibition of Na/Ca exchange (increase in Calcium increases contraction!) |
|
|
Term
| How does the Na/K pump maintain membrane potentials? |
|
Definition
For every ATP consumed, 3Na bind on cytosolic side and are transported out, in exchange for 2 extra-cellular K molecules (maintains extra-cellular Na concentration high).
** target of Quabain and Cardiac Glycosides (Digoxin and Digitoxin; used to increase cardiac contraction). |
|
|
Term
| What is the functional location of each of the 4 types of collagen protein? |
|
Definition
Must abundant protein in body!
Be (So Totally) Cool, Read, Books
I- Bone, Skin, Tendon...dentin, fascia, cornea, wound repair (90%)
II- Cartilage (hyalin, vitreous body and nucleus pulposis)
III- Reticulin (skin, blood vessels, uterus, fetal tissue, granulation tissue)
IV- Basement Membrane or basal lamina |
|
|
Term
| What is common about Osteogenesis imperfecta, Ehlers-Danlos Syndrome and Alport syndrome? |
|
Definition
OI, EDS and AS ALL involve collagen defects.
1) Osteogensis imperfecta is an issue with Collagen 1 (bone, skin, tendons)
- Blue sclera and brittle bones
2. vascular type of EDS is an issue with Collagen 3 (reticulin in blood vessels, uterus, skin, granulation tissue)
- Join hypermobility and MSK pain chronically
3. Alport is an issue with type IV collagen (basement membrane)
- glomerulonephritis, endstage kidney disease, and hearing loss |
|
|
Term
| How is collagen synthesized/processed and where does each step take place? |
|
Definition
1-4 in fibroblasts
5-6 outside of fibroblasts
1. RER: Synthesis of alpha chains involving pre-pro-collagen (Gly-X-Y polypeptide, where X-Y are proline or lysine)
2. ER: Hydroxylation of proline and lysine (need Vitamin C)
3. ER: Glycosylation of pro-alpha chain hydroxylysine residues and formation of pro-collagen via hydrogen and disulfide bonds (Triple helix of 3 alpha chains)
4. Exocytosis of procollagen into extracellular space
5. Proteolytic processing of procollagen into insoluble "tropocollagen"
6. Cross-linking of tropocollagen by covalent lysine-hydroxylysine cross-linkage (lysyl oxidase) to make collagen fibrils |
|
|
Term
| Which steps of collagen synthesis require Vitamin C and Lysyl oxidase, respectively? |
|
Definition
1) Vitamin C is required for Hydroxylation of prolone and lysine residues on preprocollagen alpha chains in fibroblasts (ER)
2) Lysyl oxidase is responsible for cross-linkage lysine and hydroxylysine residues in staggered molecules of tropocollagen in the extracellular space (forming collagen fibrils!) |
|
|
Term
| What are the 3 major steps of PCR? |
|
Definition
1) Denaturation
2) Annealing (primers)
3) Elongation (heat-stable polymerase)
smaller molecules travel further on gel |
|
|
Term
| Why might you perform a southwestern blot? |
|
Definition
| DNA-binding proteins (labeled oligonucleotide probes to identify transcription factors) |
|
|
Term
|
Definition
antigen-antibody reactivity
ex) Look for HIV antibodies , but confirm with WB
1) Patients blood probed with
- test antigen (tests for immune recognition)
- test antibody (tests for antigen) |
|
|
Term
| Why might you use a FISH assay? |
|
Definition
| Look for fine-scale genetic alterations in chromosomes that are missed by karyotype (microdeletions) |
|
|
Term
| You are studying a novel molecule and need to clone it. What 4 steps are involved in this process? |
|
Definition
1) Isolate eukaryotic mRNA (post-RNA processing)
2) Expose to RT to produce cDNA
3) Insert cDNA into bacterial plasmid containing antibiotic resistance gene
4) Surviving bacteria on antibiotic medium produce cDNA library
- surviving colonies will have insert. |
|
|
Term
| What is the difference between constitutive and conditional transgenic animal modeling? |
|
Definition
1) Constitutive involves random insertion of gene
2) Conditional is targeted insertion or deletion through homologous recombination with mouse gene
** Cre-lox system can be used (antibiotic-inducible promotors) to study embryonic-lethal genes ** |
|
|
Term
| How does RNAi work and why might you use it? |
|
Definition
Synthesize dsRNA to complementary mRNA and transfect into human cells to promote degradation of mRNA.
knock down production of particular proteins in vivo. |
|
|
Term
Which of the following cannot be resolved by Karyotyping?
a. size
b. arm-length ratio
c. morphology
d. SNP
e. banding pattern |
|
Definition
Can perform on blood, amniotic fluid, bone marrow or placental tissue to diagnose chromosomal imbalances
D. SNPs
Much too small and must be resolved by microArray of possibly by FISH. |
|
|
Term
Which of the following is NOT a fat soluble vitamin?
a. A
b. C
c. D
d. E
e. K |
|
Definition
b- Vitamin C is not fat soluble.
All Dogs Eat Kale.
A- Retinol
D- Bones
E- Antioxidant for Erythrocytes
K- Koagulation (Warfarin is antagonist)
** Absorption depends upon gut (ileum) and pancreas** |
|
|
Term
Which of the following is NOT a cause of fat soluble vitamin deficiency?
a. Cystic Fibrosis
b. Sprue
c. Rickets
d. Mineral oil intake |
|
Definition
C- Rickets is CAUSED BY lack of vitamin D, calcium or phosphate, and causes soft bones that are prone to breakage.
a) CF- CFTR mutations lead to production of thick mucous that damages pancreas and inhibits absorptive function.
b) Sprue- immune cross-reaction to consumption of gliadin protein found in gluten that is deamindated by tissue transglutaminase, leading to inflammatory damage of ilium.
c) Mineral oil- Laxative |
|
|
Term
Which of the following water-soluble vitamins are not washed out of the body?
a. B1
b. B2
c. Folate
d. B5
e. Biotin |
|
Definition
c- Folate (as well as B12) are stored in the liver.
Water Soluble Vitamins
B1 (thiamine:TPP)
B2 (Riboflavin: FAD, FMN)
B3 (Niacin: NAD+)
B5 (Pantothenic acid: CoA)
B6 (Pyridoxine: PLP)
B12 (Cobalamin)
C (Ascorbic acid)
Biotin
Folate |
|
|
Term
A patient presents with dermatitis, glossitis and diarrhea.
What should you do to treat? |
|
Definition
Likely diagnosis is a B-complex deficiency. So determine which B vitamins are low and give those as supplement
B1 (Thiamin: TPP)
B2 (Riboflavin: FAD, FMN)
B3 (Niacin: NAD+)
B5 (Pantothenic acid: CoA)
B6 (Pyridoxine: PLP)
B12 (Cobalamin) |
|
|
Term
Vitamin A
Function?
Deficiency?
Excess? |
|
Definition
Fat-Soluble
Retinol-found in liver and leafy vegetables
F- Antioxidant, Visual pigment, Epithelial differentiation into specialized tissues, prevents squamous metaplasia, treat measles and AML (M3)
D- Night blindness, dry skin
E- Arthralgia, fatigue, headache, skin changes, sore throat, alopecia, TERATOGENIC/cleft palate and cardiac |
|
|
Term
| Why must a pregnancy test be done before prescribing isotretinoin for acne? |
|
Definition
| Isotretinoin is a Vitamin A (retinol) derivative, and it can be teratogenic (cardiac issues and cleft palate) |
|
|
Term
Vitamin B1
Function?
Deficiency? |
|
Definition
Water-soluble (thiamine)
F- Cofactor for
1) PDH (glycolysis)
2) aKG DH (TCA)
3) Tranketolase (HMP shunt)
4) Branched-chian AA DH
D- Impaired glucose breakdown (ATP depletion) affects brain and heart first
**Seen in malnutrition and alcoholism**
1) Wernicke-Korsakoff (confusion, opthalmoplegia and ataxia with permanent memory loss)
2a) Beriberi (Wet)- High-output cardiac failure, edema
2b) Beriberi (Dry)- Polyneuritis, symmetrical muscle wasting |
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|
Term
Vitamin B2 (riboflavin)
Function?
Deficiency? |
|
Definition
F- Cofactor in ox/red (FADH2 to FAD and FMN..makes 2ATP)
B2= 2ATP
D: 2 C's of B2
1) Cheilosis- inflammation of lips, scaling and fissures at corners of mouth (also seen in iron deficiency)
2) Corneal vascularization |
|
|
Term
Vitamin B3 (Niacin)
Function?
Deficiency?
Excess? |
|
Definition
F- NAD+, NADP+ (used in redox). Derived from tryptophan in B6-dependent reaction.
D-Glossitis and Pellegra (if severe)
3 D's of B3
1) Diarrhea
2) Dementia
3) Dermatidis
E- Facial flushing (due to pharmacologic doses for hyperlipidemia) |
|
|
Term
Which of the following is NOT a major cause of Pellegra?
a. Hartnup disease
b. Malignant carcinoid syndrome
c. Macrocytic anemia
d. INH |
|
Definition
C- Macrocytic, megaloblastic anemia results from B12 (cobalamin) deficiency and can lead to irreversible neurological damage
A- Hartnup disease involves a decrease in tryptophan absorption, which prevents B3 synthesis
B- MCS increases tryptophan metabolism, which means there is less to synthesize B3 from
D- INH (Isoniazid) used as part of RIPE treatment for TB can cause B6 (Pyridoxone) depletion, which is required for B3 synthesis from Tryptophan (also causes polyneuropathy) |
|
|
Term
Vitamin B5 (Pantothenate)
Function?
Deficiency? |
|
Definition
"Pento" (5) thenate
F- Essential component of CoA (cofactor for acyl transfers) and Fatty Acid Synthase
D- Dermatitis, Enteritis, Alopecia, Adrenal insufficiency |
|
|
Term
Vitamin B6 (Pyridoxine)
Function?
Deficiency? |
|
Definition
F-
1) Converted to PP, a COFACTOR in transamination (ALT and AST), decarboxylation reactions and glycogen phosphorylase
2) SYNTHESIS of Cystathinione, Heme, Niacin, Histamine and GABA
D- Convulsions, hyper-irritability, peripheral neuropathy (inducible by INH and oral contraceptives).
Sideroblastic anemia due to impaired Hb synthesis and Fe excess. |
|
|
Term
| Why might a patient get Sideroblastic anemia from taking INH for TB treatment? |
|
Definition
INH induces B6 (Pyridoxine) depletion, which causes peripheral neuropathy, irritability and sometimes sideroblastic anemia.
- B6 is critical for heme synthesis (d-ALA synthase), and important element of hemoglobin, which coordinates with iron.
- Impaired Hb synthesis and excess iron cause sideroblastic anemia. |
|
|
Term
Vitamin B12 (Cobalamin)
Function?
Deficiency? |
|
Definition
Water-soluble vitamine found in animal products and Synthesized by microorganisms (stored in liver)
Detect etiology with Schilling's test
F- Cofactor for
1) Homocysteine methyltransferase (transfers CH3 groups as methylcobalamin)
**B6 is required for Cysteine synthesis from Homocysteine
2) Methylmalonyl-CoA mutase
D- Macrocytic, megaloblastic anemia, hypersegmented PMNs, neurologic symptoms (parasthesia, subacute combined degeneration) due to abnormal myelin
** if prolonged, NS damage is irreversible** |
|
|
Term
Which of the following would NOT cause macrocytic anemia?
a. Chrohn's disease
b. Lack of intrinsic factor
c. Malignant Carcinoid syndrome
d. Sprue
e. Dyphyllobothrium latum |
|
Definition
We are looking for causes of B12 deficiency here
C- Malignant Carcinoid Syndrome causes an increase in tryptophan metabolism, which would decrease B3 synthesis (perhaps leading to pellagra with diarrhea, dermatitis and dementia)
a. Chrohn's leads to absense of terminal illeum, which would cause malabsorption of B12
b. Lack of intrinsic factor, a glycoprotein produced by parietal cells of the stomach, could result from pernicious anemia or gastric bypass and would prevent B12 absorption in the terminal ileum
D. Celiac sprue, which is characterized by damage to terminal ileum because of immune cross-reaction to gliadin that has been modified by tissue glutaminase, would prevent absorption of B12.
e. Cestode tapeworm found in freshwater fish that causes malabsorption (Give Praziquantel) |
|
|
Term
Folic acid
Function?
Deficiency? |
|
Definition
Water-soluble vitamin found in green leaves and stored in liver (smaller pool than B12)
F- Converted to THF, a co-enzyme for 1-C transfer/methylation reactions
- Synthesis of N-bases in DNA and RNA (pyrimidines)
D- Macrocytic, megaloblastic anemia; NO neurological symptoms (unlike B12 deficiency).
** Most common deficiency in US, seen in alcoholics and pregnant women (give supplement), as well as Phenytoin, sulfonamides and MTX** |
|
|
Term
Which of the following is NOT associated with a Folic Acid deficiency?
a. Caused by MTX consumption
b. Causes neurological symptoms
c. Common in pregnancy
d. Issues with DNA/RNA synthesis |
|
Definition
B- You see macrocytic anemia with Folic acid deficiency, but UNLIKE B12 deficiency, there are no neurological symptoms.
a. MTX (as well as Phenytoin and Sulfonamide) consumption has been associated with Folic acid deficiency
C. It is very common in pregnancy (can cause neural tube defects), as well as in alcoholics
D. Folic acid is converted to THF, which is important for methylation reactions is synthesis of nitrogenous bases (Your DNA loves green leaves!) |
|
|
Term
| Why might you a patient exhibit abnormal autonomic responsiveness (i.e epinephrine-related) issues with Folate deficiency? |
|
Definition
S-adenosyl-methionine is required for conversion of NE to Epinephrine
ATP + methionine= SAM (methyl donor man)
Since methionine regeneration is dependent upon Folate (THF) and Vitamin B12, SAM synthesis also depends upon these water-soluble vitamins. |
|
|
Term
| How does S-adenosyl-methionine relate to anabolic metabolism? |
|
Definition
SAM serves as "methyl transfer man" for Anabolic pathways( critical for conversion of Norepineprhine to Epinephrine, and also converts Methionine to Homocysteine.
Methionine is regenerated from Homocysteine by Homocysteine methyltransferase, which requires a B12 cofactor, and the coenzyme, Folic Acid (this is why B12/Folate deficiency can lead to SAM deficiency) |
|
|
Term
| How does S-adenosyl-methionine relate to anabolic metabolism? |
|
Definition
SAM serves as "methyl transfer man" for Anabolic pathways( critical for conversion of Norepineprhine to Epinephrine, and also converts Methionine to Homocysteine).
Methionine is regenerated from Homocysteine by Homocysteine methyltransferase, which requires a B12 cofactor, and the coenzyme, Folic Acid (this is why B12/Folate deficiency can lead to SAM deficiency) |
|
|
Term
Biotin
Function?
Deficiency? |
|
Definition
Avidin in Eggs binds Biotin
F- Cofactor for carboxylation enzymes
1) Pyruvate carboxylase- Pyruvate (3C) to OAA (4C)
2) Acetyl-CoA carboxylase- Acetyl-CoA (2C) to malonyl-CoA (3C)
3) Proprionyl-CoA carboxylase- Proprionyl-CoA (3C) to methylmalonyl-CoA (4C)
D- Rare, but causes Dermatitis, alopecia, enteritis (antibiotic use or excessive injection of raw eggs). |
|
|
Term
| Why might eating a large amount of raw eggs cause alopecia, enteritis and dermatitis? |
|
Definition
This triad is seen in a Biotin deficiency (co-factor for carboxylation)
Raw eggs have Avidin in them, which strongly binds Biotin. |
|
|
Term
Vitamin C
Function?
Deficiency?
Excess? |
|
Definition
F- Antioxidant in fruits and vegetables
1) Facilitates iron absorption by keeping Fe2+ reduced
2) Necessary for hydroxylation of proline and lysine in collagen synthesis
3) Necessary for dopamine B-hydroxylase, which converts dopamine to NE.
D- Scurvey- wollen gums, bruising, hemarthrosis (bleeding into joint spaces), anemia, poor wound healing and weakened immune response
E- Nausea, vomiting, diarrhea, fatigue, sleep problems.
- Iron toxicity in predisposed individuals (transfusions or hereditary hemochromatosis) |
|
|
Term
Vitamin D
Function?
Deficiency?
Excess? |
|
Definition
D2- ergocalciferol- plants
D3- cholecalciferol- milk and sun-exposed skin
25-OH D3= storage form (liver)
1,25-(OH)2 D3 (Calcitriol)= active form (kidney)
F- Increases intestinal absorption of calcium and phosphate, increasing bone mineralization
D-
- Rickets in children (bending bones)
- Osteomalacia in adults (soft bones)
- Hypocalcemic tetany
- Breast milk has decreased vitamin D (supplement dark-skinned patients)
E- Hypercalcemia, hypercalciuria, loss of appetite, stupor
** Seen in sarcoidosis (increased activation of vitamin D by epithelioid macrophages). |
|
|
Term
Vitamin E
Function?
Deficiency? |
|
Definition
F- Antioxidant that protects erythrocytes and membranes from free-radical damage
D- Increases fragility of erythrocytes (hemolytic anemia), muscle weakness, posterior column and spinocerebellar tract demyelination
** Similar to how Vitamin B12 deficiency can cause macrocytic anemia and lead to demyelination in severe combined degeneration of spinal chord** |
|
|
Term
Vitamin K
Function?
Deficiency? |
|
Definition
Synthesized in intestinal flora, but given by injection to neonates to prevent hemorrhage!
**Warfarin is antagonist**
F- Catalyzes y-carboxylation of glutamic acid residues on various proteins concerned with blood clotting (synthesis of factors II, VII, IX, X and protein C and S.
D- Neonatal hemorrhage with increased PT and aPTT (measure of clotting time), but normal bleeding time (sterile intestines do not produce vitamin K).
Also occurs after prolonged broad-spectrum antibiotic use. |
|
|
Term
|
Definition
F- Essential for 100+ enzyme activity (zinc finger transcription factor motif, especially)
D- Delayed wound healing, decreases in adult hair, dysgeusia (taste), anosmia (smell), predispose to alcoholic cirrhosis. |
|
|
Term
Which of the following is not true regarding ethanol metabolism?
1. NAD+ is the limiting reagant
2. Disulfiram (Antibuse) can lessen hangover symptoms
3. Alcohol Dehydrogenase operates via zero-order kinetics
4. Fomepizole inhibits Alcohol Dehydrogenase and is given as an antidote for methanol or ethylene glycol poisoning |
|
Definition
2. Disulfiram inhibits Acetaldehyde Dehydrogenase, leading to acetaldehyde accumulation, which INCREASES hangover symptoms.
Ethanol Metabolism:
-2 Steps (each consumes 1 NAD+) : 1 in cytosol and 1 in mitochondria
- Cytosol step: Ethanol to Acetaldehyde with AlcDH
- Mitochondria step: Acetaldehyde to Acetate with AcetDH |
|
|
Term
| What are the 2 major reactions of ethanol metabolism? |
|
Definition
**Each consumes 1 NAD+ (limiting), making 1NADH**
1) Ethanol to Acetaldehyde in Cytosol with Alcohol DH (0-order kinetics, meaning that it all enzymes appear "saturated")
2) Acetaldehyde to Acetate in Mitochondria with Acetaldehyde DH |
|
|
Term
Why do you see each of the following in Ethanol Hypoglycemia?
1) Fatty Acid Synthesis
2) Hepatic Fatty Change
3) Increased Ketone production
4) Acidosis |
|
Definition
Ethanol increases NADH:NAD+ ratio in liver, causing
- Pyruvate to Lactate (Glycolysis)- produces 1 NAD+
- OAA to Malate (TCA cycle)- produces 1 NAD+
1) Overproduction of malate increases NADPH (malate shuttle), increases fatty acid synthesis
2) Inhibition of gluconeogenesis (no OAA or Pyruvate) and stimulation of fatty acid synthesis promotes fatty change
3) Depletion of OAA shuts down TCA, shunting aCoA into ketone production
4) Lactate production |
|
|
Term
| What is the major difference between Kwashiorkor and Marasmus? |
|
Definition
Both are malnutritive states
1) Kwashiorker is lack of PROTEIN
- MEAL (Malnutrition, Edema, Anemia, Liver (fatty liver because there are no apolipoproteins))
2) Marasmus is energy malnutrition resulting in MUSCLE WASTING, loss of sub-q fat and variable edema |
|
|
Term
What metabolic reactions occur in each of the following structures?
1. Mitochondria
2. Cytoplasm
3. Both |
|
Definition
1. Mitochondria
- Fatty acid oxidation (B-oxidation),
- Acetyl CoA production
- TCA
- Ox/Phos
2. Glycolysis, FAS, HMP shunt, protein synthesis (RER), steroid synthesis (SER)
3. HUGs take 2
- Heme synthesis, Urea cycle, Gluconeogenesis |
|
|
Term
All of the following are correct regarding Enzyme terminology, EXCEPT:
1) Carboxylases transfer CO2 groups with the help of biotin
2) Dehydrogenases reduce substrates
3) Phophatates remove phosphate groups from substrate
4) Phosphorylases add inorganic phosphate onto substrate without ATP. |
|
Definition
2) Dehydrogenases such as (PDH) OXIDIZE substrates by removing hydrogen (they are oxidizing agents, and they are also the species being reduced)
Remember, oxidation involves the addition of Oxygen (loss of electrons)
**Phosphorylases don't take ATP, but kinases do!** |
|
|
Term
What is the rate-determining enzyme for each of the following Metabolic Processes?
1. Glycolysis
2. Gluconeogenesis
3. TCA Cycle
4. Glycogen synthesis
5. Glycogenolysis |
|
Definition
1. PFK-1
2. F-16-BP
3. Isocitrate DH
4. Glycogen synthase
5. Glycogen phosphorylase |
|
|
Term
What is the rate-determining enzyme for each of the following Metabolic Processes?
1. HMP shunt
2. De novo pyrimidine synthesis
3. De novo purine synthesis
4. Urea cycle |
|
Definition
1. Glucose-6-phosphate-DH (G6PDH)
2. Carbamoyl phosphate synthetase II
3. Glutamine-PRPP amidotransferase
4. Carbamoyl phosphate synthetase I |
|
|
Term
What is the rate-determining enzyme for each of the following Metabolic Processes?
1. Fatty Acid synthesis
2. Beta-oxidation
3. Ketogenesis
4. Cholesterol Synthesis |
|
Definition
1. Acetyl-CoA carboxylase (ACC)
2. Carnitine acyltransferase I
3. HMG-CoA synthase
4. HMG-CoA reductase |
|
|
Term
How much ATP is produced by each of the following Glycolysis reactions?
1) Aerobic Glycerol-3-phopshate shuttle in muscle
2) Aerobic Malate-Aspartate shuttle in heart/liver
3) Anaerobic |
|
Definition
1) 30 ATP
2) 32 ATP
3) 2 ATP per glucose molecule |
|
|
Term
Which activated carriers handle each of the following molecules?
1) Phopshoryl
2) Electrons
3) Acyl
4) CO2
5) 1-carbon units
6) Methyl group
7) Aldehydes |
|
Definition
1) ATP
2) NADH, NADPH, FADH2
3) CoA and lipoamide
4) Biotin (remember in Carboxylase reaction)
5) THF
6) SAM
7) TPP- thiamine pyrophosphate |
|
|
Term
| What are the universal electron acceptors and how are these used metabolically? |
|
Definition
Nicotinamides (NAD+ from B3 and NADP+) and Flavin nucleotides (FAD+ from B2)
1) NAD+ is used in catabolic processes to carry reducing equivalents away as NADH
2) NADPH (HMP shunt) is used in anabolic processes (steroid and FA synthesis) as a supply of reducing equivalents
- Also in respiratory burst, P-450 and Glutathione reductase |
|
|
Term
| What are the 4 uses of NADPHD? |
|
Definition
1. Anabolic reactions (steroid and FA synthesis)- source of reducing equivalents
2. Respiratory Burst
3. P-450 (drug metabolism)
4. Glutathione reductase |
|
|
Term
| What are the major differences between Hexokinase and Glucokinase? |
|
Definition
Both phosphorylate glucose to G6P for Glycolysis (1) or Glycogen Synthesis (2)
1) Hexokinase
- low Km (high affinity), low Vmax (low capacity)
- Un-induced by insulin
- Feedback inhibited by G6P
2) Glucokinase found in Liver and B-cells of pancreases.
- High Km (low affinity), and High Vmax (high capacity)
- induced by insulin
- Phosphorylates excess glucose, making the liver a buffer for blood-glucose levels |
|
|
Term
| How does the liver serve as a "buffer" for increasing blood-glucose levels? |
|
Definition
When there is excess glucose, Glukokinase (only in liver and beta cells of pancreas) phosphorylates it in the liver, thereby sequestering it.
**First step in glycogen synthesis** |
|
|
Term
What is the net production of ATP and electron carriers in Glycolysis?
- Which steps involve consumption of ATP ?
- Which steps produce ATP? |
|
Definition
2ATP and 2NADH (along with 2 pyruvate, 2 H20 and 2H+)
1) ATP-consuming
- G (Hexokinase) G6P
- F6P (PFK-1) F1,6BP
2) ATP-producing
- 1,3BPG (Phosphoglycerate kinase) 3-PG
- Phosphoenolpyruvate (Pyruvate K) Pyruvate
- Pyruvate (PDH) A-CoA |
|
|
Term
| Describe the process of de novo synthesis of purine nucleotides. |
|
Definition
PURe As Gold (A/G)
1) Ribose-5 phosphate reacts with ATP to form PRPP (sugar and phosphate)
**PRPP can be added to Orotic acid (arising from Carbamoyl phosphate) to make Pyrimidines, OR converted to IMP for denovo or salvage purine synthesis**
2) IMP is converted top AMP or GMP
**Requires GAG amino acids (glutamate, aspartate, glycine) and THF** |
|
|
Term
| Describe the process of de novo synthesis of pyrimidine nucleotides. |
|
Definition
**Requires Aspartate and THF**
As opposed to Purine synthesis, Pyrimidine synthesis starts with a temporary base (Orotic acid), to which PRPP (Sugar phosphate) is added.
1) Carbamoyl phosphate is converted to Orotic acid (temporary base)
2) Orotic acid is added to PRPP to form UMP, which is phosphorylated to UDP.
3) UDP is reduced by ribonucleotide reductase to form dUDP or CTP
4) dUDP becomes dUMP and then dTMP (via Thymidylate synthase, in a THF-dependent reaction)
**DHF is converted back to THF (Dihydrofolate reductase) and is then methylated to be reused** |
|
|
Term
What step of nucleotide synthesis does each of the following drugs interfere with?
1) Hydroxyurea
2) 6-MP
3) 5-FU
4) MTX
5) Trimethoprim |
|
Definition
1) Inhibits ribonucleotide reductase, the enzyme responsible for reducing UDP to dUDP in de novo pyrimidine synthesis.
**Used in sickle cell anemia to make HbF
2) Blocks de novo purine synthesis by interfereing with nucleotide interconversion
3) Inhibits thymidylate synthase, which is responsible for convverting dUMP to dTMP (final step in pyrimidine synthesis, which requires THF)
4) Inhibits dihydrofolate reductase, which regenerates THF used up in thymidylate synthase reaction to produce dTMP in pyrimidine synthesis.
5) Inhibits bacterial DHFR (like 4), decreasing dTMP |
|
|
Term
| Describe the basics of the purine salvage pathway |
|
Definition
Recovers bases and nucleosides that are formed during degradation of RNA and DNA. (Important since some tissues cannot undergo de novo synthesis)
1) Adenine and Guanine are converted to AMP or GMP (HGPRT)
2) GMP and AMP can become Inosinic acid (IMP), which becomes Inosine
- Hypoxanthine also becomes IMP (HGPRT)
**In Lesch-Nyhan, you have no HGPRT, so there is no conversion of Guanine to GMP or Hypoxanthine to IMP. Guanine and Hypoxanthine both go to Xanthine and then to Uric acid**
3) If AMP is converted to adenosine, it can be converted to Inosine via Adenosine deaminase (ADA)
**Without ADA, Adenosine builds up and causes feedback inhibition of Ribonucleotide reductase, so you get SCID** |
|
|
Term
Which of the following is NOT shared by both eukaryotic and prokaryotic DNA replication?
1) Semi-conservative
2) Continuous and Discontinuous
3) Involves Okazaki fragments
4) Replication begins at a consensus sequence of base pairs |
|
Definition
4- This is characteristic of Eukaryotes only.
In both, you get semi-conservative, continuous and discontinuous (okazaki) replication |
|
|
Term
| What is the replication fork and what occurs there? |
|
Definition
Y-shaped region along DNA template where leading and lagging strangs are synthesized.
Helicase unwinds dsDNA at the fork and ssDNA binding proteins prevent re-anealing |
|
|
Term
| Describe discontinuous replication of DNA |
|
Definition
3' to 5' replication where short Okazaki fragments are synthesized from an RNA primer (Primase) and later joined by DNA ligase to form the complementary DNA strand.
Occurs 5' to 3' for each "fragment", but "reads" template from 5' to 3' overall. |
|
|
Term
| What is the major difference between nucleotide excision and base excision repair of ssDNA errors? |
|
Definition
1) NER replaces bulky adducts that are usually due to photodamage (messed up in Xeroderma pigmentosum)
- Endonucleases remove portion of ssDNA, Poli fills it back in and ligase joins it up.
2) BER
- Minor, single base errors are recognized by specific glycosylases, which remove the bases (spontaneous or toxic deamination repair)
- Apurinic/Apyrimidinic endonuclease cuts the dNA at the AP sites and then the gap is filled in and repaired similarly to NER. |
|
|
Term
| Describe the functional organization of a generic gene. |
|
Definition
Written 3' to 5' (since mRNA is transcribed 5' to 3')
1) Enhancer region, where transcriptions factors may bind and alter expression)
- Enhancer/repressor regions can be anywhere, even in introns, just not exons!
2) Promoter region, where RNA Poli and other t-factors bind to DNA (upstream of the gene locus with TATA and CAAT boxes)
3) Coding region
- Introns and exons
4) Termination signal
- AATAAA |
|
|
Term
| How to ATP-tRNA and GTP-tRNA differ in their functions during protein synthesis? |
|
Definition
1) ATP-tRNA is for Activation (charging)
- aminoacyl tRNA synthetase uses ATP to charge the tRNA, which binds to the A site in the ribosomal complex
2) GTP-tRNA "Gripping and Going places" during translocation
- GTP-hydrolysis leads to assembly of of 40S subunit with initiator tRNA (via activation of elongation factors) |
|
|
Term
| How does Digoxin increase cardiac muscle contractility? |
|
Definition
1) Inhibits Na/K pump in basolateral membrane, preventing Na+ efflux from cell in exchange for K+
2) Resting membrane potential rises, and since intracellular Na+ is high, it cannot be taken up by the cell in exchange for Ca2+
3) Accumulation of Ca2+ in cells increases contraction |
|
|
Term
| Which step in collagen synthesis is disrupted in Scurvy, Osteogenesis imperfects and Ehlers-Danlos syndrome, respectively |
|
Definition
1) Hydroxylation of lysine and proline residues on pre-pro-collagen in fibroblast ER requires Vitamin C, which is lacking.
2) OI: Deficiency in Type 1 collagen
- Problem with glycosylation of pro-alpha-chain hydroxylysine residues in fibroblast ER during formation of triple helix/ pro-collagen (hydrogen and disulfide bonds between 3 alpha chains)
- Multiple fractures (brittle bones), Blue sclerae (translucent connective tissue over sclerae), Hearing loss (inner ear bones), Dental imperfections (dentin)
2) EDS: Defect in type V (most common) or III collagen
- Problem is outside fibroblasts, with protealytic processing of pro-collagen to form tropocollagen, which will ultimately form collagen fibrils (lysil oxidase-mediated)
- Hyper-extensible skin, bleeding and hyper-mobile joints
- 6 types with variable inheritance, some causing joint dislocation, berry aneurysms and organ rupture.
- |
|
|
Term
Why might a child present with multiple fractures, difficulty hearing, dental imperfections and blue sclerae?
Which form of this disease is most fatal? |
|
Definition
Osteogenesis imperfects (1:10,000)- Often confused for abuse!
- Defect in collagen 1 processing (in fibroblasts, during glycosylation to form triple helix), so you hit Bone (ear and brittle bones), Skin, Tendons, Dentin (teeth), Corneae (blue sclera)
Type II is fatal in utero or in the neonatal period |
|
|
Term
Child presents with easy bleeding/bruising.
On PE, they have hyperextensible skin and hypermobile joints.
What genetic syndrome are you concerned about? |
|
Definition
Ehlers-Danlos- Type V or III collagen synthesis defect (proteolytic processing of pro-collagen in extracellular space to tropocollagen, which can form fibrils via lysyl oxidase.
- 6 types. Inheritance and severity varies (can be AD, AR)
- May be associated with joint dislocation, berry aneurysms and organ rupture. |
|
|
Term
| What disease is associated with hereditary nephritis, ocular disturbanes and deafness? |
|
Definition
| Alport syndrome- Most commonly X-linked recessive defect in collagen IV (BM in kidney, ears and eyes). |
|
|
Term
| What do Marfan's syndrome and Emphysema have in common? |
|
Definition
Elastin defects
Elastin is a stretchy protein (non-hydroxylated proline and glycine) within lungs, large arteries , elastic ligaments, vocal cords and ligamenta flava.
1) Marfan
- AD Fibrillin-1 defects- fibrillin is a scaffolding protein for tropoelastin
2) Emphysema
- When caused by alpha-1-anti-trypsin deficiency, elastase is free to chew up elastin in lung tissue. |
|
|
Term
True or False:
SNPs can be picked up on microarray |
|
Definition
True
- Thousands of nucleic acid sequences are arranged in grids and DNA/RNA probes are hybridized to chip and scanned for complementary binding. |
|
|
Term
| How is vitamin A used therapeutically? |
|
Definition
**Teratogenic**
1) Measles (Rubeola virus)
2) AML- M3 (acute promyelocytic)
3) Acne and wrinkles |
|
|
Term
| What is the difference between wet and dry beri beri? |
|
Definition
Both are Thiamine (B1) deficiencies (cofactor for PDH, aKG-DH, tranketolase, BCAA DH)
1) Wet
- High-output CF (dilated cardiomyoapathy) and edema
2) Dry
- Polyneuritis, symmetrical muscle wasting (denervation)
**Differentiated from Wernicke-Korsakoff, which is CNS issue with ataxia, opthalmoplegia and confusion (medial dorsal thalamus and mammillary bodies)** |
|
|
Term
| Which vitamins are known to be deficient in a patient on INH? |
|
Definition
TB treatment (RIPE)
B3 (Pellegra) and B6 (heme synthesis and many others)
1) B6 is classically low
2) B3 requires B6 to convert Tryptophan to B3, so B3 is low as well. |
|
|
Term
| What are the major metabolic reactions that require B12? |
|
Definition
Co-factor
1) Homocysteine Methyltransferase
- Takes methyl group from m-THF and gives it to Homocysteine to form Methionine
2) Methylmalonyl-CoA mutase
- Methylmalonyl-CoA handles Odd chain fatty acids and makes them into succinyl CoA for the TCA cycle |
|
|
Term
Which of the following drugs does NOT cause folate deficiency?
1) Phenytoin
2) Sulfonamides
3) Trimethoprim
4) MTX
5) Flouroquinolones |
|
Definition
| 5: Inhibits DNA gyrase- nothing to do with THF or folate. |
|
|
Term
| What vitamins are required for the different steps of catecholamine synthesis? |
|
Definition
1) Dopamine conversion to NE (dopamine beta-hydrxylase) requires Vitamin C
2) NE to EPi requires SAM, which is generated from ATP + Methionine
- Methionine synthesis requires folate and B12 (homocysteine methyltransferase) |
|
|
Term
Which of the following is NOT a major function of vitamin C?
1) Catecholamine production
2) Iron absorption
3) Elastin synthesis
4) Collagen synthesis |
|
Definition
3- Elastin does not involve vitamin C
1) Dopamine to NE conversion requires vitamin C (dopamine beta hydroxylase)
2) Keeps iron in reduced (Fe2+) state
4) Hydroxylation of lysine and proline in pre-pro-collagen requires vitamin C |
|
|
Term
| Why do patients with Sarcoidosis get hypercalcemia |
|
Definition
| Epithelioid macrophages have 1-alpha-hydroxylase to produce 1,25 OH vitamin D, which increases calcium and phosphate reabsorption |
|
|
Term
| Why might a patient present with disgeusia and anosmia, as well as hair loss? |
|
Definition
Zinc deficiency.
May predispose to alcoholic cirrhosis, so stop that drinking!
Also watch out for wound healing and hypogonadism. |
|
|
Term
| What is the use of Fomepizole and Disulfiram, respectively? |
|
Definition
1) Fomepizole inhibits alcohol DH (cytoplasm) and is an antidote for methanol or ethylene glycol poisoning
2) Inhibits Acetaldehyde DH (mitochondrial), leading to acetaldehyde accumulation and contributing to hangover symptoms |
|
|
Term
| What 2 reactions regenerate NAD+ during Alcoholic hypoglycemia? |
|
Definition
Alcohol and Acetaldehyde DH use up NAD+, so you need to make more.
Pyruvate goes to Lactate (acidosis)
OAA goes to Malate (NADPH production and fat synthesis) |
|
|
Term
Which of the following reactions do not take place (at least in part) in the mitochondria?
1) Beta oxidation of fatty acids
2) Urea cycle
3) Gluconeogenesis
4) Glycolysis
5) Acetyl CoA production |
|
Definition
4- Glycolysis, fatty acid synthesis, HMP shunt, protein synthesis and steroid synthesis take place in the cytoplasm
- Gluconeogenesis and Urea cycle (as well as heme synthesis) take place in both the mitochondria and the cytosol.
- Acetyl CoA production, beta oxidation, TCA cycle and ox/phos take place in the mitochondria ONLY |
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|
Term
| Where does glycolysis occur and what is the net reaction? |
|
Definition
Glycolysis is in the cytosol
1) Start 2) Finish
1) Glucose + 2Pi + 2ADP + 2NAD+
2) 2 pyruvate + 2ATP + 2NADH+ 2H + 2H2O |
|
|
Term
| What are the major reactions in glycolysis and which of them consume/produce ATP? |
|
Definition
- uses ATP and + produces it
- RLS is PFK-1
1) Glucose (hexokinase/glucokinase) G6P (-) IRREVERSIBLE
2) G6P becomes F6P spontaneously
3) F6P (PFK-1) F 1,6-BP (-)
- IRREVERSIBLE
4) F 1,6-BP becomes Gl-3P
5) Gl-3P becomes 1,3-BPG
6) 1,3-BPG (Phosphoglycerate K) 3-PG (+++)
7) 3-PG becomes 2-PG and then PEP
8) PEP (PK) Pyruvate (++)
- IRREVERSIBLE |
|
|
Term
How is glycolysis regulated by each of the following?
1) ATP
2) Glucose-6-phosphate
3) Fructose-6-phosphate
4) Alanine
5) Citrate
6) AMP
7) F-2,6-BP
8) NADH
9) acetyl-CoA |
|
Definition
1) Inhibited (stimulated by ADP/AMP)
2) Inhibits hexokinase
3) Inhibits glucokinase
4) Inhibits glycolysis
5) Inhibits glycolysis
6) Stimulates
7) Stimulates
8) Inhibits
9) Inhibits |
|
|
Term
| How does F2,6BP regulate glycolysis? |
|
Definition
F-2,6-BP is in equilibrium with F-6-P, and is a stimulator of glycolysis (along with PFK-2)
- It is produced by FBPase2 (glycolysis)
- It is consumed by PFK2 (gluconeogenesis)
1) Fasting state (i.e. you need glucose)
- glucagon increases cAMP/PKA
- PKA activates FBPase-2, driving F-2,6-BP towards F-6-P and gluconeogenesis
2) Fed state
- Insulin inhibits cAMP/PKA signalling
- Low PKA increases PFK-2 activity, driving F-6-P towards F-2,6-BP, which stimulates PFK-1 and glycolysis. |
|
|
Term
| How does F2,6BP regulate glycolysis? |
|
Definition
F-2,6-BP is in equilibrium with F-6-P.
- It is produced by FBPase2 (glycolysis)
- It is consumed by PFK2 (gluconeogenesis)
1) Fasting state (i.e. you need glucose)
- glucagon increases cAMP/PKA
- PKA activates FBPase-2, driving F-2,6-BP towards F-6-P and gluconeogenesis
2) Fed state
- Insulin inhibits cAMP/PKA signalling
- Low PKA increases PFK-2 activity, driving F-6-P towards F-2,6-BP, which stimulates PFK-1 and glycolysis. |
|
|
Term
| What are the components and co-factors required for the Pyruvate DH complex |
|
Definition
Complex is activated by exercise (Increased NAD/NADH ratio, ADP and Ca2+)
Pyruvate + NAD+ + CoA (PDH) aCoA + CO2 + NADH
Composed of 3 enzymes
E1: TPP (B1)
E2: Lipoate and CoA (B5, pantothenate)
E3: FAD (B2) and NAD+ (B3) |
|
|
Term
| What reactions utilize PDH and aKG-DH complexes, respectively, and what is similar about them? |
|
Definition
Both require the same 5 cofactors (TPP, NAD, FAD, lipoic acid, CoA)
1) PDH produces aCoA from pyruvate
2) aKG-DH produces succinylCoA from aKG |
|
|
Term
| Why do you see vomiting, rice water stools and garlic breath in a patient with arsenic poisoning? |
|
Definition
| Arsenic inhibits lipoic acid, a major cofactor in the aKG-DH and PDH reactions, which produce sCoA and aCoA, respectively (ATP in the TCA cycle) |
|
|
Term
Which of the following factors would NOT activate the PDH complex?
1) Excercise
2) Decreased NAD+/NADH ratio
3) Increased calcium
4) Increased ADP |
|
Definition
PDH makes aCoA from pyruvate to start the TCA cycle (needs NAD, FAD, lipoic acid, CoA/B5 and TPP)
2: If NAD+ is scarce, it means you need more glucose, not more ATP (the TCA cycle will make 2.5 additional NADH) |
|
|
Term
| What are the clinical manifestations of a PDH deficiency and how do you treat? |
|
Definition
Neurological Defects/Give ketogenic nutrients (Lysine and Leucine + high fat diet)
Congenital or Acquired (Thiamine deficiency)
PDH makes acetyl-CoA from pyruvate to start the TCA cycle.
Low PDH will have back-up of pyruvate, which will sent to lactate (LDH). |
|
|
Term
| Why give Leucine and Lysine to treat PDH deficiency? |
|
Definition
| They are purely ketogenic aminoacids and will treat Neurological defects resulting from lactic acidosis and ATP deficiency. |
|
|
Term
| Describe the 4 pathways of pyruvate metabolism. |
|
Definition
1) ALT
- Alanine carries amino groups to liver from muscle
2) Pyruvate carboxylase (mitochondria)
- OAA replenishes TCA cycle or is used in gluconeogenesis
- Requires CO2 and ATP
3) PDH (mitochondria)
- Makes aCoA, CO2 and NADH for TCA
- requires NAD,FAD, TPP, CoA, Lipoic acid)
4) LDH (cytosol)
- Anaerobic glycolysis (RBC, leukocyte, kidney medulla, lens, testes and cornea) to produce lactate and NAD+ |
|
|
Term
| Describe the overall reaction and major steps of the Kreb's cycle. |
|
Definition
Citrate Is Kreb's Starting Substrate For Making Oxaloacetate
Makes 2.5 NADH, 1.5 FADH2, 2CO2, and 1 GTP per acetyl-CoA, which is the same as
10ATP/acetyl-CoA (2x everything per glucose)
1) Pyruvate (PDH) Acetyl-COA
2) Acetyl-COA (2C) + OAA (4C) (citrate synthase) Citrate (6C)
3) Citrate (6C) becomes Isocitrate (6C)
4) Isocitrate (6C) (IC-DH) a-KG (5C)
- RLS, produces CO2 + NADH
5) aKG (5C) (aKG-DH) succinyl CoA (4C)
- Produces CO2 and NADH
6) sCoA (4C) becomes Succinate
- CoA + GTP produced
7) Succinate (4C) becomes Fumarate (4C)
- Produces FADH2
8) Fumarate (4C) becomes Malate (4C)
9) Malate (4C) becomes OAA (4C)
- Produces NADH
10) OAA (4C) + aCoA (2C) becomes Citrate (6C) again |
|
|
Term
| Which steps of the TCA cycle produce NADH, CO2, FADH2 and GTP, respectively? |
|
Definition
1) NADH
- IS (IS-DH) aKG
- aKG (aKG-DH) sCoA
- Malate to OAA
2) CO2
- IS (IS-DH) aKG
- aKG (aKG-DH) sCoA
3) FADH2
- Succinate to Fumarate
4) GTP
- sCOA to Succinate makes GTP and coenzyme A |
|
|
Term
| Describe how ATP is actually produced by oxidative phosphorylation |
|
Definition
1NADH makes 3ATP and 1FADH makes 2ATP
Passage of electrons produces a proton gradient, which drives the production of ATP and H2O by ATP-synthase
**NADH electrons enter mitochondria via malate-aspartate (heart and liver= 32 ATP) or glycerol-3-phosphate (muscle= 30 ATP) shuttles
**FADH2 enters at complex II |
|
|
Term
How do each of the following poisons impeded oxidative phosphorylation?
1) Rotenone
2) Cyanide
3) Carbon Monoxide
4) Oligomycin
5) Aspirin
6) 2,4 DNP |
|
Definition
1) Complex 1 inhibitor: electron transport
- Decrease proton gradient and block ATP synthesis
2) CN- and CO are cytochrome oxidase (IV) inhibitors
- Antimycin A is a complex III inhibitor
4) ATP synthase inhibitor, causing an increase in the proton gradient, but without ATP production (no electron transport)
5-6) Uncoupling agents
- Increase membrane permeability, dissipating H+ gradient and increasing O2 consumption
- Electron transport continues (heat) |
|
|
Term
| Describe how an incoming NADH molecule is consumed in the inner mitochondrial membrane to produce 3ATP. |
|
Definition
1) 2 electrons are removed from NADH at complex 1 (NADH-DH) and given to ubiquinone (coQ)
- gradient generation begins
2) Complex II (succinate DH) take electrons from FADH to produce FAD+, but does not generate a proton gradient.
3) Complex III (Cytochrome C associated)
- Gradient is enhanced
- 2 electrons given from Q to Cytochrome C)
4) Complex IV (cytochrome C oxidase)
- 4 electrons are removed from 4 molecules of cytochrome c and transferred to molecular oxygen (O2), producing two molecules of water. |
|
|
Term
| What are the irreversible enzymes of gluconeogenesis? |
|
Definition
Occurs in liver (and kidney and intestinal epithelium)
Pathway Produces Fresh Gluclose
1) Pyruvate carboxylase (mitochondria)
- Pyruvate to OAA
- Requires biotin, ATP
- Activated by acetyl-CoA
2) PEP carboxykinase (cytosol)
- OAA to PEP
- Requires GTP
3) F 1,6-Bisphosphatase (cytosol)
- F 1,6-BP to F6P
4) Glucose 6 phosphatase (ER)
- G6P to glucose |
|
|
Term
| Why can gluconeogenesis NOT take place in muscle? |
|
Definition
| No Glucose-6-Phosphatase (final step) |
|
|
Term
| How does OC and EC fatty acid metabolism contribute to gluconeogenesis, respectively? |
|
Definition
1) Odd-chain FA
- Yield 1 propionyl-CoA during metabolism, which can enter the TCA cycle (methylmalonyl coA mutase, which requires B12), undergo gluconeogenesis (succinate to fumarate to malate to OAA and out) and serve as a glucose source
2) Even-chain FA
- Cannot produce new glucose, since they yield only acetyl-CoA equivalents |
|
|
Term
| Describe the reactions of the HMP shunt and identify its functional purpose. |
|
Definition
RLS= G6P-DH
Provides
- NADPH from abundant G-6-P, which is used for reductive reactions (glutathione in RBCs)
- Ribose for nucleotide synthesis and glycolytic intermediates
1) Oxidative (irreversible)
- G6P (G6P-DH) Co2 + 2 NADPH + Ribulose 5-P
2) Non-oxidative (reversible)
- Ribulose-5P (Transketolase + B1) Ribose-5-P + G3P + F6P |
|
|
Term
| What is the "respiratory burst" and why does it matter? |
|
Definition
Immune response in PMNs and Monocytes
1) O2 (NADPH oxidase) O2-
2) O2- (SOD) H2O2
- H2O2 may be broken to H2O and O2 by bacterial catalase (e.g. staph)
3) H2O2 + Cl- (MPO) HOCl-
**WBCs of patients with CGD can utilize H2O2 generated by invading organisms to convert it to ROIs** |
|
|
Term
| What are the 3 critical enzymes involved in the respiratory burst? |
|
Definition
1) NADPH oxidase (O2 to O2-)
- CGD
2) SOD (O2- to H2O2)
3) MPO (H2O2 + Cl- to HOCl-) |
|
|
Term
| What are the major reactions of the Glutathione oxidation/reduction pathway and why is it important? |
|
Definition
Defense against oxidative damage from ROIs (converts H2O2 to H2O)
To regenerate reduced GSH that can protect, you need NAPDH, which is produced by the HMP from G6P
1) GSH reduces H2O2 to H2O, and is oxidized to GSSG (Catalase/GSH peroxidase)
2) In order for GSSG to be reduced to GSH by GSH reductase, NADPH from HMP must be oxidized to NADP+
3) NADPH is regenerated by G6P conversion to 6PG (G6PD) |
|
|
Term
| What are the genetics, pathophysiology and clinical presentation of a G6PD deficiency. |
|
Definition
Bite cells (splenic macrophages) and Heinz bodies (oxidized Hb ppt in RBC)
1) X-linked recessive defect (most common human enzyme deficiency- increases malarial resistance in blacks)
2) No NADPH available to regenerate reduced GSH to protect RBCs from ROIs
3) Intrinsic, extravascular hemolytic anemia in response to Fava beans, Drugs (sulfonamides, phenytoin, primaquine, anti-TB drugs) and Infection. |
|
|
Term
| What is the difference between Essential fructosuria and Fructose intolerance? |
|
Definition
2 major disorders of fructose metabolism
Fructose (FK) F1P (AldoB) DHAP and Glyceraldehyde
1) Essential fructosuria
- AR defect in fructokinase (fructose to F1P)
- Benign since fructose is not trapped in cells
2) AR deficiency in Aldolase B
- F1P accumulates, causing a decrease in available Pi, which inhibits glycogenolysis and gluconeogenesis
- Hypoglycemia, jaundice, cirrhosis and vomitting |
|
|
Term
Patient presents with hypoglycemia, jaundice, vomiting and signs of cirrhotic liver disease.
Serum and urine levels of Fructose-1-P are very high.
What is going on and how do you treat? |
|
Definition
1) Fructose intolerance- AR deficiency in Aldolase B, the enzyme that converts F1P to Dihydroxyacetone phosphate and Glyceraldehyde in the liver.
2) Restrict fructose and sucrose intake |
|
|
Term
| Describe the normal metabolism of fructose. |
|
Definition
A way for fructose to bypass rate-limiting PFK-1 step in glycolysis!
1) Fructose (Fructokinase) F1P
2) F1P (Aldolase B) Dihydroxyacetone-P and Glyceraldehyde
3a) DHAP conveted to Glyceraldehyde-3P
3b) Glyceraldehyde can be converted to Glycerol (NADH to NAD) or to Glyceraldehyde-3-P (Triose kinase)
4) G-3-P enters glycolysis to produce pyruvate |
|
|
Term
| What are the clinical manifestations of a Galactokinase deficiency and what is the pathophysiological basis? |
|
Definition
AR deficiency leading to Galactitol accumulation leading to infantile cataracts (relatively mild compared to classic galactosemia)
- Galactose is converted to either Galactose-1-P (Galactokinase) OR Galactitol (Aldose reductase)
Without the kinase, you go the other direction. |
|
|
Term
| Describe the pathophysiology of Classic galactosemia. How does it relate to Fructose intolerance? |
|
Definition
Similar mechanisms: Uridyl transferase in Galactoseria is similar to Aldolase B in Fructose intolerance.
Treated similarly: reduce lactose and galactose vs. fructose and sucrose
1) AR deficit in Uridyltransferase, so Galactose-1-P (produced from Galactose by Galactokinase) builds up and DOES NOT become Glucose-1-P for glycolysis.
- Like in Galactokinase deficiency, Galactitol accumulates in lens of eye
- You get failure to thrive, jaundice, hepatomegaly, infantile cataracts adn mental retardation.
EXCLUDE galactose and lactose (galactose + glucose) from diet. |
|
|
Term
| What is the reaction catalyzed by Uridyl transferase and how does it relate to 4-epimerase? |
|
Definition
1) Catalyzes conversion of Galactose-1-P to Glucose-1-P
- Without G-1-P, you cannot send galactose metabolism to glycolysis and you get classic galactosemia
2) UT uses up UDP-Glu (making UDP-Gal), and uses 4-epimerase to regenerate UDP-glucose.
- UDP-glucose is converted to glycogen for storage |
|
|
Term
| Why does hyperglycemia cause kidney and retina damage, but not liver and ovarian damage? |
|
Definition
1) Kidney, Schwann cells, Lens and Retina have aldose reductase (converts Glucose and NAPDH to Sorbitol), so sorbitol accumulates
2) Liver and Ovaries (as well as seminal vesicles) has Aldose reducase AND Sorbitol DH, so they can take Sorbitol and NAD+, and make Fructose. |
|
|
Term
Patient presents with bloating, cramps and complains of diarrhea
True or False: Lactase deficiency can be age-dependent and/or hereditary.
How do you treat? |
|
Definition
True
Hereditary in AA and Asians, due to loss of brush border enzyme (May also follow gastroenteritis)
- Avoid dairy products or add lactase pills
**The diarrhea is osmotic, from lactose buildup** |
|
|
Term
What are the essential amino acids?
Which are glucogenic, ketogenic and mixed AAs? |
|
Definition
All AA in protein are "L" form and essential ones must be supplied in diet.
1) Glucogenic: Met, Val, Arg, His
2) Ketogenic: Leu, Lys
3) Both: Ile, Phe, Trh, Trp |
|
|
Term
| What are the acidic and basic amino acids? |
|
Definition
1) Acidic (negative charge)
- Asp and Glu
2) Basic (positive charge)
- Arg (most basic), Lys, His (no charge at body pH)
- Need Arg and His for growth
- Arg and Lys are increased in histones, which bind negatively charged DNA |
|
|
Term
| Describe the basic steps of the Urea cycle. What is the rate-limiting enzyme? |
|
Definition
Ordinarilly, Careless Crappers Are Also Frivolous About Urination
*Carbamoyl phosphate synthase 1 is RLS*
Begins in mitochondria and then heads to Cytosol.
Nitrogen produced during amino acid catabolism (pyruvate and acetyl CoA processing) begins cycle
Mitochondria (Liver)
1) NH4 + CO2 (CPT-1 + 2 ATP) Carbamoyl phosphate
**CP can go to pyrimidine synthesis or the Urea cycle**
2) CP + Ornithine (OTCase) Citrulline
Cytoplasm
1) Citrulline + Aspartate (NH4 donor) (Arginosuccinate synthetase) Arginosuccinate
2) Arginosuccinate (Arginosuccinase) Fumarate and Arginine
3) Arginine (Arginase + water) Urea and Ornithine
4) Urea goes to kidney and Ornithine combines with more CP to form Citrulline. |
|
|
Term
| How is ammonium taken from the muscle to the liver? |
|
Definition
Cori Cycle: Removes nitrogen from the muscle to the liver, where it can undergo the urea cycle and be removed by the kidneys.
START
1) Amino acids (NH3) become a-keto acids and aKG becomes glutamate (NH3)
2) Glutamate (NH3) is converted back to aKG and Pyruvate forms Alanine (NH3) and Lactate
3) Lactate and Alanine (NH3) travel to the liver, and re-combine to form Pyruvate (which becomes glucose and can travel back to muscle)
- Alanine transfer of NH3 to aKG in liver forms glutamate (NH3), which enters the Urea cycle. |
|
|
Term
Patient presents with tremor, slurring of speech, somnolence, vomiting and evidence of neurological dysfunction with blurred vision.
You suspect cerebral edema and draw a serum NH4+ level, which is high.
What is going on, why might this happen, and how do you treat? |
|
Definition
1) Hyperammonemia
- Excess NH4+ depletes aKG (forming glutamate), so the TCA cycle shuts down
2) Acquired (liver disease) or Hereditary (urea cycle enzyme deficiencies)
3) Limit protein.
- Give Benzoate or Phenylbutyrate (both bind AA and lead to excretion)
- Lactulose to acidify GI and trap NH4+ for excretion. |
|
|
Term
| Why might you give a patient with OTCase deficiency lactulose? |
|
Definition
They have hyperammonemia.
lactulose will acidify the GI and trap NH4+ for excretion.
Other options include protein restriction, and AA excreters (Benzoate and Phenylbutyrate) |
|
|
Term
| What is the most common urea cycle disorder and how does it manifest? |
|
Definition
High urinary/serum orotic acid with low BUN and symptoms of hyperammonemia (Orotic aciduria would NOT have hyperammonemia).
OTC deficiency: X-linked recessive (all others are AR)
- You can't convert CP + Ornithine to Citrulline, so you get Hyperammonemia
- Excess CP is converted to Orotic acid (part of pyrimidine synthesis) |
|
|
Term
What signalling molecules are derived from each of the following AA?
1) Phe
2) Trp
3) His
4) Gly
5) Arg
6) Glut |
|
Definition
1) Converted to Tyrosine in catecholamine synthesis (Tyr, DOPA, Dopamine, NE, EPi)
2) Can become B3 (B6) or 5-HT (BH4)
- 5-HT becomes melatonin as well
3) Histamine (B6 mediated)
4) Porphyrin (B6) and then heme
5) Creatinine, Urea and NO
6) GABA (B6) or Glutathione |
|
|
Term
| What cofactors are required to produce Epinephrine from Phenylalanine? |
|
Definition
THB, B6, vitamin C and SAM
1) Phe to Tyrosine (BH4)
2) Tyrosine to DOPA (BH4-tyrosine hydroxylase)
3) DOPA to Dopamine (B6- dopa decarboxylase)
4) Dopamine to NE (Vitamin C: Dopamine b-hydroxylase)
5) NE to Epi (SAM: PMNT) |
|
|
Term
Which of the following compounds is not required to make Epinephrine from Phenalalynine?
1) B3
2) B6
3) THB
4) SAM
5) Vitamin C |
|
Definition
1- Niacin requires B6 for its production from Tryptophan.
2) B6 (DOPA decarboxylase)
3) THB (Phenalalynine and Tyrosine hydroxylases)
4) SAM (PMNT)
5) Vitamin C Dopamine beta-hydroxylase |
|
|
Term
Which of the following is NOT derived from arginine?
1) Urea
2) Nitric Oxide
3) Glutathione
4) Creatinine |
|
Definition
| 3- Comes from glutamate (as does GABA) |
|
|
Term
Which of the following amino acids is required to produce melatonin?
1) Arginine
2) Glycine
3) Phenylalanine
4) Tryptophan
5) Histidine |
|
Definition
4- Makes Niacin (B6) and 5-HT (THB)
- 5-HT becomes melatonin
1) Arginine: Urea, Creatine and NO
2) Glycine: Porphyrin (B6)...Heme
3) Tyrosine..Thyroxine and the catecholamines
5) Histamine (B6) |
|
|
Term
| What are the functions of B6? |
|
Definition
Co-factor
1) Tryptophan metabolism to Niacin
2) DOPA decarboxylase
3) Histamine synthesis from His
4) GABA from glutamate
5) Porphyrin from Glycine |
|
|
Term
| Describe the major steps and cofactors of Catecholamine synthesis. |
|
Definition
1) Phenylalanine (Phenylalanine hydroxylase + THB) Tyrosine
2) Tyrosine (Tyrosine hydroxylase + THB) DOPA
3) DOPA (DOPA decarboxylase + B6) Dopamine
- Inhibited by Carbidopa
4) Dopamine (Dopamine beta-hydroxylase + Vitamin C) NE
4) NE (PMNT + SAM) Epi
- stimulated by cortisol |
|
|
Term
| What are the breakdown products of Dopamine, NE and Epi, respectively? |
|
Definition
Can be key in Pheochromocytoma diagnosis.
1) Dopamine: HVA
2) NE: VMA
3) Epi: Metanephrine |
|
|
Term
Why might a baby have a musty body odor and shows signs of mental retardation, growth retardation, fair skin and eczema?
Why do you screen for this condition 2-3 after birth? |
|
Definition
PKU- Aromatic amino acid metabolism
1) Decreased phenylalanine hydroxylase or THB (malignant PKU), where Tyrosine becomes essential
- Excess Phe leads to phenylketones in urine
2) You screen 2-3 days after, since it is normal at birth because of maternal enzyme
**Stop the consumption of Phe (Nutrasweet) and increase Tyrosine** |
|
|
Term
| Which neonatal hereditary metabolic disorder requires decreased Nutrasweet consumption (aspartame)? |
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Definition
| PKU- You can't metabolize Phe, so you need to cut it out and supplement with Tyrosine instead |
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Term
| What are the complications associated with pregnancy in a woman with PKU? |
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Definition
| Microcephaly, Mental retardation, Growth retardation and Congenital heart defects. |
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Term
What enzyme is deficiency in each of the following congenital presentations?
1) Musky odor and mental/growth retardation
2) Brown pigmented sclera, dark connective tissue and black urine
3) Lack of melanin and increased risk of skin cancer
4) Kyphosis, lens subluxation, mental retardation and homocystinuria |
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Definition
1) PKU- Phenalalanine hydroxylase or THB (malignant PKU)
2) Alkaptonuria (AR): Homogentisic acid oxidase (tyrosine to fumarate)
3) Albinism (AR): Tyrosinase or defective Tyrosine transporters
4) Homocystinuria (AR)
- Cystathione synthase deficiency or decreased affinity for B6
- Homocysteine methyltransferase |
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Term
| Why do patients with Alkaptonuria have drak urine/connective tissue and debilitating arthralgias? |
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Definition
Homogentisic acid oxidase deficiency
- HAO is critical for degeneration of Tyrosine to Fumarate, so Tyrosine builds up and is converted to melanin (Tyrosinase)
- Homogentisic acid is toxic to cartilage, so you get arthralgia. |
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Term
| What is the difference in inheritance patterns between ocular albinism and classic albinism? |
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Definition
1) Ocular is X-linked recessive
2) Classic is variable due to locus heterogenity
- Tyrosinase deficiency (AR) or Defective tyrosine transporters
- Can result from lack of neural crest migration as well. |
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Term
| What are the 3 ways you can get Homocystinuria (describe the pathway)? |
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Definition
Presents with Mental reatardation, Osteoporosis, tall stature, Kyphosis and lens subluxation (down and in), as well as Atherosclerosis.
Homocysteine can become one of 2 things:
1) Methionine (Homocysteine methyltransferase + B12)
2) Combine with serine to form Cystathione (Cystathione synthase + B6)
- Cystathione is converted to Cysteine.
- Cysthione synthase deficiencies (Lower Met in diet and raise Cys, B12 and folate in diet)
- Decreased CS affinity for B6 (increase B6 in diet)
- Homocystein methyltransferase deficiency (reduce Cys in diet). |
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Term
Which of the following is NOT true regarding Homocystinuria?
1) Can make Cysteine an essential Amino acid
2)Lens subluxation
3)Short stature with scoliosis
4) Mental retardation
5) Can be caused by Homocysteine methyltransferase deficiency |
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Definition
3: These patients have tall stature with Kyphosis
1) True in Cystathione synthase deficiency
2) True: down and in
4) True
5) True: Will build up behind (No Met) and go towards Cysteine pathway |
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Term
| What is the pathophysiology and common complications for a patient with urine that smells like maple syrup? |
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Definition
I Love Vermont maple syrup from maple trees (with branches)
1) Blocked branched amino acids (Ile, Leu, Val) due to decreased alpha-ketoacid-DH.
2) Increased alpha-ketoacids in blood causes severe CNS defects, mental retardation and death. |
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Term
| How do you treat a patient who has an AR condition that causes him to have cysteine kidney stones (renal staghorn calculi and hexagonal crystals)? |
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Definition
1) Cystinuria is common (1:7000) defect in renal tubular amino acid transporter for cysteine, ornithine, lysine and arginine in the PCT
- Excess "Cystine" in urine causes stone formation
2) Acetazolamide to alkalinize urine
**Cystine is 2 cysteines connected by disulfide bond** |
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Term
| Why does Hartnup disease cause dementia, dermatitis and diarrhea? |
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Definition
Pellagra because of AR defect in neutral AA transporter on renal and intsetinal epithelial cells.
Increased Trp excretion in urine and decreased absorption leads to decreased B3 synthesis (which relies on Trp and B6) |
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Term
| How does Insulin:Glucagon balance alter Glycogen storage (mechanistically)? |
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Definition
Matter of whether Glycogen phosphorylase is active (Glycogenolysis) or not
1) Glucagon>>Insulin (fasted state)
- cAMP/PKA activation and phosphorylation of Glycogen phosphorylase kinase (activating)
- GPK stimulates glycogenolysis by activating GP
**GPK is also activated by Ca/calmodulin in muscle to coordinate with demand
2) Insulin >> Glucagon (fed)
- RTK dimerizes and activates Protein phosphatase, which de-phosphorlyates GPK (inactivating)
- Glycogen storage is favored |
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Term
| What is the basic structure and synthetic process involved in forming Glycogen? |
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Definition
Stored in Liver
1) Branches have a-(1,6) bonds and linkages have a-(1,4)
2)
Storage
- Glucose-6-P converted to G1P
- G1P (UDP-glucose pyrophosphorylase) to UDP-glucose
- UDP-G (**Glycogen synthase**) Glycogen
- Glycogen (branching enzyme) Branched form
Glycogenolysis to maintain blood sugar
- Branched form (Glycogen phosphorylase) limit dextrin
- Limit dextrans (Debranching enzymes) to Glycogen |
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Term
| How does Glycogenolysis occur in skeletal muscle? |
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Definition
Glycogen...Glucose-1-P...G-6-P...Glucose
**Calcium/calmodulin activates Phorphosrylase kinase so that glycogenolysis occurs in coordination with muscle activity** |
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Term
What is the role of each of the following enzymes in Glycogenolysis/synthesis?
1) Glycogen phosphorylase
2) Debranching enzyme
3) Lysosomal a-1,4 glucosidase
4) Glucose-6-phosphatase
5) Branching enzyme |
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Definition
1) Glycogen phosphorylase in skeletal muscle (activated by Ca/Calmodulin) converts Glycogen to Limit dextrin (4 glucose residues in branched confirmation)
2) Takes limit dextrin to Glucose
- Can be phosphorylated by glucokinase
3) Breaks glycogen linkages (small amount) to form Glucose and Pi
4) Takes Glucose-6-Phosphate to Glucose + Pi
5) G-1-P from G-6-P can be converted to UDP-glucose, which is converted to glycogen by Glycogen synthase and Branching enzye.
3) |
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Term
| What are the major glycogen storage diseases and what is the deficient enzyme in each? |
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Definition
Very Poor Carbohydrate Metabolism
1) Von Gierke's disease
- Glucose-6-phosphatase
2) Pompe's disease
- Lysosomal alpha-1,4,-glucosidase (acid maltase)
3) Cori's disease
- Debranching enzyme (a-1,6-glucosidase)
4) McArdle's disaease
- Skeltal muscle glycogen phosphorylase |
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Term
Which glycogen storage disease is deficient in each of the following enzymes and what is the pathogenesis?
1) Glucose-6-phosphatase
2) Alpha-1,6,-glucosidase
3) Lysosomal alpha-1,4-glucosidase (acid maltase)
4) Skeletal muscle glycogen phosphorylase |
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Definition
Very Poor Carbohydrate Metabolism
1) Von Gierke (type 1)
- Can't get glucose from G-6-P after it is produced from glycogen
- Fasting hypoglycemia, increased glycogen in liver, high blood lactate and hepatomegaly
2) Cori's disease (III)- De-branching enzyme
- Milder form of type 1 with normal blood lactate levels
- Intact gluconeogenesis
3) Pompe's (II) (trashes the Pump)
- No lysosomal degradation of glycogen to glucose
- Cardiomegaly and systemic findings with early death (heart, liver and muscle)
4) McArdle's disease (IV)
- Increase glycogen in muscle, but cannot break it down, leading to painful cramps, myoglobinuria (with exercise) |
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Term
Which glycogen storage disease is associated with each of the following clinical pictures?
1) Fasting hypoglycemia, hepatomegaly and normal blood lactate levels.
2) Severe fasting hypoglycemia, hepatomegaly and lactic acidosis
3) Muscle cramps with exercise
4) Cardiomegaly, liver/muscle failure and eath |
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Definition
Very Poor Carb Metabolism
1) Cori's disease (III)
- De-branching (alpha 1,6 glucosidase) is gone, and you have a less severe form of Von Gierke's, since gluconeogensis is still in tact).
2) Von Gierke's
- Glucose-6-Phosphorylase is gone, so you can't get glucose from limit dextrans (liver) of Glucose-1-P (muscle)
3) McArdle's disease (IV)
- No Glycogen phosphorylase in muscle, so glycogen builds up and causes cramps
4) Pompe's disease
- No lysosomal alpha-1,4-glucosidase (acid maltase)
- trashes the "PUMP" |
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Term
There are many lysosomal storage diseases.
Name the enzyme associated with each clinical presentation.
1) Peripheral neuropathy of hands/feet, angiokeratomas and CV/renal disease
2) Hepatosplenomegaly, aspectic femoral necrosis and bone crises with macrophages that like like "crumpled tissue paper"
3) Progressive neurodegeneration, hepatosplenomegaly, cherry-red macula and foam cells.
4) Progressive neurodegeneration, developmental delay, cherry-red macula and NO hepatosplenomegaly. You see lysosomes with onion skin. |
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Definition
All are "Sphingolipidoses"
1) Fabry's (XR): alpha galactosidase A
- Ceramide trihexoside accumulation
2) Gaucher's (AR): Glucocerebrosidase
- Accumulation of Glucocerebroside
3) Neimann-Pick (AR): Sphingomyelinase
- Sphingomyelin builds up
4) Tay-Sachs disease (AR): Hexosaminidase A
- GM2 ganglioside build-up |
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Term
| Which 2 lysosomal storoage diseases present with progressive neurodeneration and cherry-red maculas? |
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Definition
Ashkenazi Jews get Tay-Sachs, Neimann-Pick and some forms of Gaucher's
1) Neimann-Pick (AR: Hepatosplenomegaly and Foam cells)
- Sphingomyelinase deficiency with sphingomyelin buildup
2) Tay-sachs (AR: No hepatosplenomegaly, but onion skin lysosomes)
- Hexosaminidase A deficiency with GM2 ganglioside build-up) |
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Term
| What are the only 2 lysosomal storage diseases with XR inheritance? |
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Definition
1) Fabry's (Sphingolipidosis)
- alpha galactokinase A deficiency with Ceramide trihexose buildup
- peripheral neuropathy (hands/feed), angiokeratoma, CV/renal disease
2) Hunter's syndrome (Mucopolysaccharidosis)
- Iduronate sulfatase deficiency with Heparan sulfate and Dermatan sulfate buildup
- Aggressive behavior, no corneal clowding (vs. Hurler's), developmental delay and hepatosplenomegaly |
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Term
There are many lysosomal storage diseases.
Name the enzyme associated with each clinical presentation.
1) Peripheral neuropathy, developmental delay, optic atrophy and globoid cells.
2) Peripheral neuropathy of hands and feet with angiokeratomas
3) Central and peripheral demyelination with ataxia and dementia
4) Developmental delay, gargoylism, airway obstruction, corneal clouding and hepatosplenomegaly
5) Mild gargoylism and hepatosplenomegaly, with clear cornea's and aggressive behavior |
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Definition
Ashkenazi Jews get Tay-Sachs, Neimann-Pick and some forms of Gaucher's
1-3 are Sphingolipdoses (Krabbe's, Fabry's, Metachromatic leukodystrophy)
4-5 are mucopolysaccharidoses (Hurler's and Hunter's)
1) Krabbe's disease (AR)
- Deficient galactocerebrosidase and buildup of galactocerebroside
2) Fabry's (XR)
- Deficient alpha galactokinase A with build up of Ceramide Trihexoside
3) Metachromatic leukodystrophy (AR)
- Arylsulfatase A deficiency
- Buildup of Cerebroside sulfate
4) Hurler's (AR)
- Deficient alpha-L-iduronidase
- Buildup of dermatan and heparan sulfates
5) Hunter's (XR)
- Deficient Iduronate sulfatase
- Buildup of Dermatan and Heparan sulfates |
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Term
| Which lysosomal storage diseases cause peripheral neuropathy? |
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Definition
Those that involve Galactose
1) Fabry's (XR): alpha galactosidase A
- Buildup of Ceramide trihexoside causes peripheral neuropathy in hands and feet (along with angiokeratomas and CV/renal disease)
2) Krabbe's (AR): Galactocerebrosidase
- Galactocerebrosides cause peripheral neuropathy, optic atrophy and developmental delay |
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Term
| How can you tell between Hunter's and Hurler's syndromes? |
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Definition
Both are mucopolysaccharidosis (Dermatan and Heparan sulfate) lysosomal storage diseases, but "Hunter's see clearly."
Hurler's has corneal clouding (a-L-iduronidase deficiency)
Hunter's is milder and does NOT (iduronate sulfatase) |
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Term
| Which lysosomal storage diseases are more common in Ashkenazi jews? |
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Definition
| Ashkenazi Jews get Tay-Sachs, Neimann-Pick and some forms of Gaucher's |
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Term
The ceramide synthesis pathway is complex.
Many lysosomal diseases arise from disruptions in this pathway.
Describe the pathway. |
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Definition
Ceramide is a membrane component that can be formed from 1)Galactocerebrosides, 2)Glucocerebrosides or 3)Sphingomyelin.
1) Sulfatides become Galactocerebrosides (Metachromatic leukodystrophy)
- Galactocerebrosides become Ceramide (disrupted in Krabbe's)
2) Gangliosides become Glucocerebrosides (Tay-Sach's)
- Ceramide trihexosides also become Glucocerebrosides (Fabry's)
- Glucocerebrosides become Ceramide (Gaucher's)
3) Sphingomyelin becomes Ceramide (Neimann Pick) |
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Term
| How are Fatty acids synthesized? |
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Definition
In the cytoplasm of cells from Citrate, with RLS by Acetyl-CoA carboxylase
1) Citrate is taken out of mitochondria by the citrate shuttle and converted to Acetyl-CoA (Citrate lyase + ATP)
2) Acetyl-CoA is converted to Malonyl-CoA by ACA carboxylase (CO2 + biotin)
3) Malonyl-CoA is converted to Palmitate, a 16C FA |
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Term
| How are Fatty acids metabolized? |
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Definition
In the mitochondria with RLS by Carnitine acyltransferase-1
1) Fatty acids and CoA become Acyl-CoA (Fatty acid CoA synthetase)
2) Acyl-CoA enters mitochondria via Carnitine shuttle and is converted to Acetyl-CoA (Acyl-CoA-DH)
** Acyl CoA is conjugated to carnitine by carnitine acyltransferase 1 on the outside and then released by carnitine acyltransferase 2 on the inside**
3) Acetyl CoA becomes Ketones and/or enters the TCA cycle |
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Term
| Describe the pathophysiological effects of a Carnitine deficiency. |
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Definition
Hypoketotic hypoglycemia with weakness and hypotonia
Carnitine is critical during fatty acid degradation, because it binds Acyl-CoA in the cytoplasm (via Carnitine acyltransferase I) and transfers it into the mitochondria, where it is released (carnitine acyltransferase 2) to form acetyl CoA (acyl-CoA-DH). Without acetyl-CoA, you don't get ketones or TCA.
Hypoketotic hypoglycemia with weakness and hypotonia |
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Term
| Describe the pathophysiological effects of a acyl-CoA-DH deficiency. |
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Definition
acyl CoA gets into the mitochondria via the carnitine shuttle during FA degradation, but it cannot be converted to acetyl CoA for ketone synthesis or TCA.
- Increased dicarboxylic acids and low ketones/glucose |
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Term
| What are beta-hydroxybutyrate and acetoacetate? Where are they produced and why do they matter? |
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Definition
Fruity breath with DKA/starvation and Acetoacetate detected in urine.
1) Ketone Bodies
- Produced in liver from HMG-CoA (using AA and FA)
- Excreted in urine (DKA or prolonged starvation)
2) Used as fuel by brain and muscle
- Brain gets 2 acetyl-CoA per ketone body |
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Term
| Why do you get ketoacidosis in prolonged starvation? What about in alcoholism? |
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Definition
1) OAA is depleted for gluconeogenesis (also seen in DKA)
- TCA shuts down and shunts glucose and FFA toward ketone body production.
2) NADH shunts OAA to malate
- Same results |
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Term
| Under what conditions might you see elevated urine ketones? |
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Definition
| Starvation, DKA (type 1 DM) and Alcoholism |
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Term
| Describe the different sources of fuel that are used up during a 2 hour exercise session. |
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Definition
1g protein or carb= 4 kcal
1g fat= 9kcal
1) First few seconds
- Stored ATP used up as Creatine phosphate spikes
- Anaerobic glycolysis begins
2) Minutes
- Anaerobic glycolysis ramps up
- Aerobic metabolism and FA oxidation begin
3) Hours
- Aerobic metabolism and FA oxidation overtake Anaerobic. |
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Term
True or False:
Equivalent mass of fat provides more energy than protein. |
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Definition
True!
1g protein or carb= 4 kcal
1g fat= 9kcal |
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Term
Describe the changes that occur in glucose handling in the following states.
1) Fed (after meal)
2) Fasting (between meals)
3) Starvation (1-3 d)
4) Starvation (after day 3) |
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Definition
1) Glycolysis and aerobic respiration dominate
- Insulin stimulates storage of lipid, protein and glycogen
2) Hepatic glycogenolysis (major)
- Hepatic gluconeogenesis, Adipose release of FFA
- Glucagon and adrenaline stimulate use of fuel reserves.
3) Starvation days 1-3
- Hepatic glycogenolysis (1 day)
- Adipose release of FFA (used by
muscle and liver)
- Hepatic gluconeogenesis from peripheral tissue lactate and alanine, and form adipose tissue glycerol and priopionyl-CoA (from odd-chain-FFA)
4) Starvation after 3 days
- Adipose stores (ketone bodies are major source for brain and heart)
- After adipose stores, vital protein is used and organs fail. |
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Term
Which of the following is the major determinant of survival after 3 days of starvation
1) Adipose stores
2) Mitochondrial oxidation efficiency
3) B12 stores
4) Liver metabolic rate |
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Definition
| 1- Ketones come from here and prevent organ protein use |
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Term
| Why can RBCs not use ketones as an energy source? |
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Definition
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Term
Describe the role of each of the following in lipid transport.
1) Pancreatic lipase
2) Lipoprotein lipase
3) Hepatic TG lipase (HL)
4) Hormone-sensitive lipase |
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Definition
1) Degrades dietary TG in small intestine, so that it may be packaged into chylomicrons
2) LPL degrades TG circulating in chylomicrons and VLDLs to FFA, which are taken up by muscle and adipose tissue.
**Chylomicron remnants are further processed by LPL and HL, and then bind remnant receptors in liver**
3) Degrades TG remaining in IDL after LPL cleaves VLDL (produces LDL)
4) Degrades TG stores in adipocytes |
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Term
| How is cholesterol esterified in the liver and what function does this process have? |
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Definition
2/3 of plasma cholesterol is taken from Liver and Intestine by Nascent HDL particles and then esterified by LCAT to produce mature HDL particles
These particles than transfer cholesterol to VLDL, IDL and LDL via Cholesterol ester transfer protein (CETP) |
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Term
What is the function of each of the major apolipoproteins?
1) E
2) A-1
3) C-II
4) B-48
5) B-100 |
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Definition
1) Binds remnant receptors on liver
- Found on all particles EXCEPT LDL
2) Activates LCAT
- Found on chylomicrons and HDL
3) Activates LPL (cofactor)
- Chylomicrons, VLDL and HDL
4) Mediates chylomicron secretion
- Chylomicrons and Remnants
5) Binds LDL receptors in liver and peripheral tissues
- Found on VLDL, IDL and LDL |
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Term
| What is the difference between LDL and HDL in terms of function? |
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Definition
LDL: B-100
- Transports cholesterol from liver to tissues (receptor-mediated endocytosis)
- Formed by LPL modification of VLDL in peripheral tissue
2) HDL: E, A-1, C-II
- Secreted by liver and intestine, and takes cholesterol from periphery to liver (to make bile acids, ect)
- Repository for apoC and apoE (needed by Chylomicron and VLDL) |
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Term
| Describe the basic steps of lipid transport in dietary metabolism |
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Definition
Dietary
1) Dietary TG is degraded by Pancreatic lipase and stored in chylomicrons (apoE, A-1, C-II and B-48) in intestine
2) Chylomicrons are cleaved by LPL (C-II), releasing FFA to adipose and peripheral tissue
3) Chylomicron remants are cleaved by HL and LPL, and then taken up by liver, where they deliver cholesterol
4) ApoE and ApoC is taken by HDL |
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Term
| Describe the basic steps of lipid transport in intrinsic cholesterol metabolism |
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Definition
1) VLDL (E, C-II, B-100) is synthesized by liver and delivers hepatic TGs to periphery
2) VLDL cleaved by LPL to IDL, which is deliverd to the liver or is cleaved by HL to LDL
3) LDL delivers hepatic cholesterol to peripheral tissues, where it is taken up by receptor-mediated endocytosis. |
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Term
Describe the pathophysiology of the following familial dyslipidemias.
1) Type I
2) Type II-a
3) Type IV |
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Definition
1) Hyper-chylomicronemia
- LPL deficiency of altered apoC-II causes pancreatitis, hepatosplenomegaly and eruptive/pruritic xanthomas (no risk of atherosclerosis).
- High Chylomicrons and elevated blood levels of TG and cholesterol
2) Hyper-cholesterolemia
- AD defect in LDL receptor causing atherosclerosis, tendonous xanthomas and corneal arcus
- High LDL and blood cholesterol
3) Hyper-triglyceridemia
- Hepatic overproduction of VLDL, causing pancreatitis
- High VLDL and high serum TG |
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Term
A 2 month old presents with failure to strive, steatorrhea, acanthocytosis, ataxia and night blindness.
What hereditary syndrome is causing this? |
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Definition
Abetalipoproteinemia
AR mutation in microsomal TG transport protein (MTP), leading to decreased B-48 and B-100
- low B-48 and B-100 means low chylomicrons and VLDL synthesis, which means that fat accumulates within enterocytes. |
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