Term
|
Definition
| Point mutations in Hb convert 2 Glus -> 2 Vals: loss of two negative charges -> decreased solubility ->Hb quaternary agglutination in RBCs -> misshapen RBCs |
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Term
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Definition
| Mutations in telomerase's RNA component. Developmental delay, increased cancer incidence |
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Term
|
Definition
| Repeat expansion (size: 60-200, 230+) of CGG trinucleotide sequence on X chromosome in 5'-UTR. |
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Term
|
Definition
| Repeat expansion (size: 60-200, 200+) of GAA trinucleotide sequence in Intron 1 |
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Term
|
Definition
| Repeat expansion (size: 36-121) of CAG trinucleotide sequence on coding region of N-terminal |
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Term
|
Definition
| Estrogen fuels tumor growth. Coactivator gene A1B1 for estrogen receptors (?) is overexpressed. |
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Term
|
Definition
| Androgen fuels tumor growth. |
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Term
| Acute promyelocytic leukemia (APL) |
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Definition
| Oncogene made by fusion of nuclear receptor (retinoic acid/Vitamin A receptor) to PML protein from chromosomal translocation. |
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Term
| Acute myeloid leukemia (AML) |
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Definition
| Oncogene made by fusion of coactivator TIF2 to MOZ protein from chromosomal translocation. |
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Term
| Spinal/bulbar muscular atrophy |
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Definition
| Androgen receptor mutation. |
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Term
| Crueztfeldt-Jakobs disease |
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Definition
| Misfolded protein in brain induces misfolding of native proteins |
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Term
| Cystic Fibrosis (some cases) |
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Definition
| Splicing disruption (some cases), either by exon skipping (missing upstream branchpoint A), splice signal mutation, cryptic splice site signal activation (frameshift mutation) |
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Term
| Hutchinson-Gilford Progeria |
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Definition
| Lamin A/C defect, sometimes caused by mutations activating cryptic splice sites. Causes advanced aging during childhood |
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Term
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Definition
| C-myc oncogene never degrades (protein causing cancer proliferation continues to be made), due to missing 3' UTR targeted-decay signals lost during chromosomal translocation. |
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Term
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Definition
| Nonsense mutation from splice site defect leads to a bad Hb that ruins all good Hb tetramers. |
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Term
| Aminoglycoside associated deafness |
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Definition
| Ototoxic antibiotics (aminoglycosides: *-mycin) interfere with mitochondrial translation. Exacerbated in individuals with defective copies of mitochondrial translation machinery components (mitochondrial rRNA, nuclear rProtein). |
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Term
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Definition
| GLUT transporter not recruited into cell membranes in muscles, adipose and heart. Glucokinase synthesis also not upregulated. Leads to hyperglycemia -> kidney disease, hypertension, atherosclerosis, blindness. |
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Term
|
Definition
| Lactic acid produced but lactate anion and proton dissociates can't diffuse out from skeletal muscle because of poor blood flow: pain. |
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Term
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Definition
| Aldolase defective; glycolysis stops and lactic acid fermentation must compensate. Leads to hypoglycermia & lactic acidosis |
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Term
|
Definition
| Gal-1-Pi-Uridyl Transferase deficient. Galacitol accumulation is cataract-forming and toxic. |
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Term
|
Definition
| G-6-Pase in liver is defective. Can't break down glycogen. Hypoglycemia, hepatomegaly, lactic acidosis, lipemia, hyperuremia (more G-6-Pi to PPP, leading also to uric acid formation). |
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Term
| Glycogen phosphorylase deficiency (liver) |
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Definition
| Glycogen phosphorylase in liver is defective. Can't break down glycogen. Hepatomegaly, mild hypoglycemia |
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Term
| Glycogen phosphorylase deficiency (muscle) |
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Definition
| Glycogen phosphorylase in muscle is defective. Can't break down glycogen. Exercise-induced muscle pain; cramps, progressive hypoglycemia. |
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Term
|
Definition
| Glu-6-Pi-Dehydrogenase is deficient. RBCs cannot make NADPH from PPP; glutathione antioxidant integrity is ruined. Hymolytic RBCs |
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Term
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Definition
| Non-enzymatic glycosylation, irreversible. HbA1c gives indication of long-term blood glucose levels: 4-6% is normal; 7-16% is diabetic. |
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Term
| Diabetic Vascular Disease |
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Definition
| AGE binds RAGE on endothelial wall. Induces chemokine production, attracting monocytes which attack oxidized LDLs. Become foamy macrophages, clogging up arteries. |
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Term
| Henderson-Hasselbach equation |
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Definition
| pH = pKa + log ([A-]/[HA]) |
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Term
|
Definition
| Competitive Inhibitor (no change in Km) |
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Term
|
Definition
Non-Competitive inhibitor
(Km stays the same, Vmax decreases) |
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Term
|
Definition
| Non-Competitive inhibitor |
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Term
|
Definition
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Term
|
Definition
-quaternary enzymes (multiple subunits, ex: hemoglobin)
- shows an S-shaped michaelis-menten curve |
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Term
|
Definition
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Term
|
Definition
| Unwinds prokaryotic DNA (helicase) |
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Term
|
Definition
| nicks 1 strand of prokaryotic DNA to relieve torsional strain |
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Term
|
Definition
| single strand binding proteins --> keep DNA from coming back together |
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Term
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Definition
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Term
|
Definition
tethers with beta clamp & replicates prokaryotic DNA in 5'-3' direction
*3'-5' exonuclease activity |
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Term
|
Definition
| replaces Pol III to remove RNA primers on prokaryotic DNA |
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Term
|
Definition
| replaces Pol III to remove RNA primers on prokaryotic DNA |
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Term
|
Definition
| cause prokaryotic replication to stop |
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Term
|
Definition
| unlinks catenated prokaryotic DNA strands |
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Term
|
Definition
| prevents DNA from binding to parent strand |
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Term
|
Definition
Primase in complex adds RNA primers
DNA Pol a adds a few nucleotides |
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Term
|
Definition
tethers with PCNA & replicates 5'-3'
*3'-5' exonuclease activity |
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Term
|
Definition
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Term
|
Definition
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Term
|
Definition
creates RNA template at end of chromosome to extend lagging strand with junk DNA
T-loops then created so that sticky ends don't bind to other chromosomes |
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Term
|
Definition
| occurs during replication |
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Term
|
Definition
After replication
Error recognition -> strand discrimination -> excision -> resynthesis -> ligation |
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Term
| Non-polyposis colorectal cancer |
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Definition
|
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Term
| Base excision repair & Direct reversal |
|
Definition
DNA glycosylase flips & removes bases -> AP endonuclease cuts bond -> DNA polymerase -> ligase
MGMT reverses methylation of guanine bases (suicide bc can only act once then is used up) |
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Term
| Polyposis colorectal cancer |
|
Definition
| error in base excision repair |
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Term
| Nucleotide excision repair |
|
Definition
Removes unrecognizable bases/bulky dimers
Damage recognition -> nuclease cleaveage -> removed with helicase -> Pol delta -> DNA ligase |
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Term
|
Definition
| error in nucleotide excision repair; sensitive to UV because can't remove thymine dimers |
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Term
|
Definition
| error in nucleotide excision repair |
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Term
|
Definition
double strand break repair uses sister chromatid during mitosis
- exonuclease cuts to make sticky ends → strand invasion by sister chromatid → DNA synthesis/sister chromatid exchange → unwinding/ligation(BLM helicase) |
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Term
| Non-homologous recombination |
|
Definition
- Synapse formed by Ku70 & Ku80
- DNA PKcs clean up staggered ends
-Ligated by LIG4 & XRCC4
-> Very error-prone and much information is lost |
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Term
| Nuclear receptor pathway hormones |
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Definition
| glucocorticoids, mineralcorticoids, estrogen, androgens, progestins |
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Term
|
Definition
1. hormone crosses plasma membrane and binds to receptor (SR)
2. SR -> HRE (hormone response element) in nucleus
3. HRE & coactivators to promoter sequence
4. mRNA transcribed |
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Term
| Steroid receptor antagonists |
|
Definition
block steroid receptor by conformational change
ex: tomoxifen used to block estrogen receptor -> stops cell proliferation in breast tissue |
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Term
| Cell surface receptor pathway |
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Definition
1. binds to receptor on plasma membrane
2. activates G protein
3. which activates cAMP
4. Which activates PKA
5. Which phosphorylates an activator in nucleus (ex CREB)
6. activator binds to enhancing or promoting region |
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Term
|
Definition
Inverted guanine added to 5' end
Recognized by NPCs for export
Prevents degradation of mRNA |
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Term
|
Definition
Poly A tail added to 3' end
Once termination sequence (AAUAAA) is recognized, mRNA transcription ends 30 bp down & poly A tail added
-prevents degradation & necessary for export through NPCs |
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Term
|
Definition
| 5' GU----A----C/U rich---AG 3' |
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Term
| Hutchinson-Gilford Progeria |
|
Definition
| point mutation in lamin A gene that causes activation of a cryptic splice site leads to premature aging (denovo mutations) |
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Term
| Translation energy requirement - scanning/initiation |
|
Definition
2 ATP for each aminoacyl-tRNA synthesis
1 GTP to unwind 5'UTR |
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Term
|
Definition
|
|
Term
| Translation energy - elongation |
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Definition
|
|
Term
| Translation energy - termination |
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Definition
|
|
Term
| Pyruvate Dehydrogenase Cofactors |
|
Definition
| TPP (need thiamin/B1); FAD, NAD, CoA, Lipoic acid |
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Term
|
Definition
1. Alanine --> transport from muscle to liver, gluocneogenesis cycle
2. Oxaloacetate --> regenerates for Krebs cycle, or pathway for gluconeogenesis
3. Acetyl-CoA --> Krebs cycle or fatty acid synthesis
4. Lactate --> Cori cycle, or end-product of anaerobic respiration |
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Term
|
Definition
a. Blood proteins water soluble
b. Membrane proteins lipid soluble. Some proteins are amphipathic.
c. Minimum solubility at isoelectric point. |
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Term
| Primary protein structure |
|
Definition
-amino acids connected carboxyl end (COO-) to amino (NH2) end via peptide bonds
-can have sulfide bridges between cysteine's |
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|
Term
| Secondary protein structure |
|
Definition
folding in patterns of alpha helices (H bond parallel) or beta sheets (H bond perpendicular)
i. Stabilized by H bonds |
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Term
| Tertiary protein structure |
|
Definition
i. H bonds
ii. Ionic bonds bw side chains (polarized AAs)
iii. Adopt lowest energy state in terms of hydrophobic interactions
iv. Sometimes mediated by chaperones if primary structure doesn’t contain all folding info |
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|
Term
| Quaternary protein structure |
|
Definition
-NO covalent bonds
-only exists with multiple subunits
-Structure stabilized by H-bonds, ionic bonds, or hydrophobic interactions |
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|
Term
|
Definition
G= Glycine
A= Alanine
Va= Valine
L= Leucine
I= Isoleucine
M= Methionine
P= Proline |
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Term
| Amino Acids - positive charge |
|
Definition
| Arginine, Histidine, Lysine |
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|
Term
| Amino Acids - negative charge |
|
Definition
Aspartic Acid
Glutamic Acid |
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|
Term
| Amino Acids - polar uncharged |
|
Definition
Serine
Threonine
Asparagine
Glutamine |
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|
Term
| Amino Acids - hydrophobic side chain |
|
Definition
Alanine
Valine
Isoleucine
Leucine
Methionine
Phenylalanine
Tyrosine
Tryptophan |
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|
Term
| Amino acids - special cases |
|
Definition
Cysteine - SH group
Selenocysteine - SeH group
Glycine - smallest, R-group = H
Proline - smallest aromatic |
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Term
| Michaelis-Menten equation |
|
Definition
V = Vmax*[S] / Km + [S]
Km = [S] at ½ Vmax |
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Term
|
Definition
mutation in RNA component of telomerase
-> developmental delay & increased cancer risk |
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|
Term
| Trinucleotide repeat diseases |
|
Definition
-Fragile X, Muscular dystrophy, spinocerebellar ataxia
-exhibit genetic anticipation because trinucleotide repeats / secondary structures are extended in subsequent replications (Okazaki fragments can replicate)
-usually CG rich because stabilized by triple H bond |
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Term
| Transcription - initiation & process |
|
Definition
Transcription factors bind to enhancer element -- interact with histone tail --chromatin remodeling - transcription factors bind to enhancer elements to recruit recruit RNA pol II & basal TFs - which bind to TATA box (30 bp before start site) - RNA pol II reads DNA 3'-5' --RNA synth 5'-3'
*Unwinding of DNA helix aided by DNA topoisomerases |
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|
Term
| RNA polymerase variations |
|
Definition
RNA pol I - large rRNAs
RNA pol II - mRNA
RNA pol III - tRNA & small rRNA |
|
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Term
|
Definition
Some TFs modify histone tails to make them more/less ammenable to transcription
-Acetylation - pro-transcription
-Methylation - anti-transcription |
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|
Term
| Nuclear receptor examples |
|
Definition
| Steroid hormones (glucocorticoids, mineralocorticoids, estrogens, androgens, progestins), thyroid hormones, retinoid (vitamin A), vitamin D |
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Term
| Functional domain of nuclear receptors |
|
Definition
| N - transcriptional modulation - DNA binding - hormone binding - C |
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Term
|
Definition
| Is an antagonist, binding & changing conformation of the steroid receptor -> inhibiting txpn by denying coactivators and txpn factors a binding site. This prevents the growth of breast cancer cells |
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Term
|
Definition
| : chromosomal translocation shortens 3’ UTR, removing sequences necessary for mRNA downregulation |
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Term
| Translation - overall process |
|
Definition
1. 40' subunit scans mRNA 5' to 3'
2. Stops at AUG sequence, binds tRNA/methionine
3. 60S subunit joins
4. elongated 5'-3' (N-C)
5. Stop codon encountered & ribosome releases R factor
6. Ribosomes recycled to start of mRNA |
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Term
|
Definition
i. A frameshift mutation will likely cause an early stop codon
ii. If a stop codon is encountered, the ribosome releases a release factor that scans for exon/exon junction complexes (EJCs) 50+ bp upstream of stop codon
iii. If a protein is encountered, the mRNA is signaled for destruction |
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Term
|
Definition
generate ATP by oxidation: breaking down carbs, fats, aa’s
Catabolic reactions usually have DEPHOSPHORYLATED enzymes |
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Term
|
Definition
utilize ATP in the synthesis of macromolecules, muscle contraction, active transport, nerve conduction and thermogenesis.
Enzymes are usually PHOSPHORYLATED |
|
|
Term
|
Definition
soluble:
i.Coenzyme A
ii.NAD
Enzyme-bound:
iii.FAD
iv.TPP (thiamine pyrophosphate)
v. Lipoic acid |
|
|
Term
|
Definition
Dephosphorylated form = active
PD Phosphorylase takes P's off
PD kinase phosphorylates
-Mg2+, Ca2+ = allosteric effector of PD phosphorylase
-NADH, AcetylCoA = positive allosteric effectors of PD Kinase (inactivate PDH)
- pyruvate, NAD, CoA = negative allosteric effectors of PDKinase (activate PDH) |
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|
Term
Malate Aspartate shuttle
Glycerol-3-phosphate shuttle |
|
Definition
| transports NADH from cytoplasm (from glycolysis) to mitochondria |
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Term
|
Definition
NADH dehydrogenase, with FeS (non-heme) & flavin (FMN)
NADH -> CoQ -> Complex III (2.5 ATP/NADH)
4H+ shuttled across memebrane |
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Term
|
Definition
Succinate dehydrogenase, FeS (non-heme)
-takes e- from FADH2 -> CoQ -> complex III (1.5 ATP/FADH2) |
|
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Term
|
Definition
Cytochrome bc1,cytochrome c reductase
FeS (non-heme)
-transports e- from Q10 -> Cyt c
Pumps 4H+ |
|
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Term
|
Definition
cytochrome aa3, cytochrome c oxidase
Heme A
pumps 4 H+
O2 = final electron acceptor |
|
|
Term
|
Definition
proton gradient driven through protein
gamma rotates
beta unit is held in place by c unit, creating frictional force and catalyzes ATP synthesis |
|
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Term
|
Definition
HOOC-hydrocarbon tail
Long, even-#’d carbon chains
Double bonds = unsaturated
o Cis bonds
o Allows for membranes to be fluid / tissues to be softer bc compounds can’t pack as tightly |
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Term
|
Definition
• Stored as triacylglycerols (triglycerides)
o Oxidized in heart, skeletal muscle, and liver for energy
o Stored in adipose tissue for later use |
|
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Term
|
Definition
Linolenic Acid (omega 3) 18:3
Linoleic Acid (omega 6) 18:2 |
|
|
Term
|
Definition
1. Acetyl CoA (mito) -> citrate/malate shuttle -> Acetyl CoA (cytosol) + NADPH
2. Acetyl CoA + ATP → (acetyl CoA carboxylase (dephosphorylated) + biotin) → malonyl CoA
3. Malonyl CoA + Acetyl CoA -> (Fatty Acid Synthase) -> Fatty Acid (ex Palmitate) |
|
|
Term
| Fatty Acid Overall rxn for C16 |
|
Definition
| Acetyl CoA + 7 Malonyl CoA + 14 NADPH -> Palmitic Acid + 7CO2 + 14 NADP + 8CoA + 6H2O |
|
|
Term
| FA elongation & desaturation |
|
Definition
C16 can be elongated (via Malonyl CoA substrate)
or desaturated (desaturases for multiple junctions) |
|
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Term
|
Definition
3-C backbone (from DHAP / Glycerol-3-P)
3 FA's (from fatty acyl CoA) |
|
|
Term
|
Definition
o Made in well-fed state
o Made in liver & intestine
o Stored in adipose tissue
-- no negative feedback - can make as much as you eat |
|
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Term
|
Definition
1. TAG broken down to glycerol (to liver for gluconeogenesis) + FFAs (Hormone-Sensitive Lipase~P)
-activated by low insulin/glucagon/epinephrine
2. FFAs transported in blood & bound by albumin
3. FFAs absorbed by liver, muscle, etc
4. Converted to fatty acyl CoA esters
5. Transported to mitochondria matrix (CPT1 & II - carnitine) |
|
|
Term
|
Definition
In mitochondria
Fatty acyl CoA --> B oxidation --> Acetyl CoA + FADH2 + NADH
Some Acetyl CoA -> HMG CoA -> Ketone Bodies |
|
|
Term
| Fatty Acid Oxidation - overall reaction |
|
Definition
Palmitoyl CoA + 7 CoA + 7 FAD + 7 NAD + 7 H2O → 8Acetyl CoA+ 7 FADH2 + 7 NADH
(total ATP from breakdown = 108) |
|
|
Term
|
Definition
Acetoacetate, β-hydroxybutyrate, Acetone
-low in well-fed
-very high in fasting state -> provides fuel to brain
-prevent muscle / protein breakdown |
|
|
Term
| Why are ketone bodies produced in fasting / diabetes? |
|
Definition
No insulin = No Krebs cycle (which is favored in well-fed state to produce ATP)
Acetyl CoA can't make glucose, so instead it makes ketone bodies
--> ketoacidosis |
|
|
Term
| Cholesterol synthesis reaction |
|
Definition
| • Acetyl CoA → HMG CoA + 2 NADPH → (HMG CoA reductase - dephosphorylated) → Mevalonic acid → → Cholesterol |
|
|
Term
|
Definition
| precursor for bile acids, steroid hormones, vitamin D, Coenzyme Q, lipid bilayer, lipoproteins |
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