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Dental Biochemistry
test #3
98
Medical
Professional
05/13/2009

Additional Medical Flashcards

 


 

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Term
What are the steps of the HIV replication process?
Definition

Entry of virus nucleocapsid into host cytoplasm

Reverse Transcription of viral RNA into DNA by viral reverse transcriptase

Integration of viral DNA with host DNA genome = provirus

Transcription of proviral DNA by host

Polymerase II in host nucleus and subsequest transportation to cytoplasm for translation

Assembly, Budding & Maturation of HIV into infectious particles

 

Term

Which region in the HIV genome codes for protease, reverse transcriptase, ribonuclease, and integrase?

 

Which region codes for nucleocapsid core and matrix proteins p24, p17, p7 and p6?

Definition

viral enxymes:  The POL region

 

 

structural proteins: The GAG region

Term
Which non-structural HIV gene is responsible for down regulating CD+ antigens and inducing cytokine production by macrophages?
Definition

NEF

-encodes negative regulatory factor

 

-deletion of non-essential NEF gene represents strategy for possible live attenuated HIV vaccine

Term

What type(s) of eukaryotic RNA polymerase are inhibited by a-amanitin, a toxin found in the poisonous mushroom Amanita phalloides? Where is each polymerase located?

A. RNA pol I

B. RNA pol II

C. RNA pol III

Definition

A. RNA pol I - Nucleolus

B. RNA pol II - Nucleoplasm

C. RNA pol III - Nucleoplasm

 

RNA polymerases II and III are inhibited by a-amanitin - II is strongly inhibited, III in high concentrations, and I not at all.

Term
Rubenstein-Taybi syndrome is caused by mutation of what gene expression-related protein?
Definition

CBP

(CREB binding protein)

Term
Each human cell has __ meters of DNA packaged into ___ chromosomes.
Definition

2 meters

23 pairs of chromosomes

Term

N-linked oligosaccharides, characteristic of plasma and membrane proteins, are always attached by a glycosylamine linkage of N-acetylglucosamine to what?

Definition
the amide nitrogen of an asparagine residue
Term

What channels open during repolarization?

 

Definition
Voltage-gated postassium channels
Term
Which channels open during depolarization?
Definition
Voltage-gated sodium channels
Term
Which voltage gated ion channels do the cocaine class of drugs block?
Definition

 

Voltage-gated Na+ channels

ex. lidocaine used as local anaesthetic - inhibits Na+ channel opening and depolarization of cell

 

- cocaine also inhibits dopamine and norEpi reuptake

Term

What are the 5 classes of Neurotransmitters?

Examples of each?

Definition

Amines: ACh, dopamine, serotonin

Amino Acids: Glutamate, glycine, GABA

Purines: ATP, adenosine

Gases: NO

Peptides: opioid peptides, somatostatin

Term

How is ACh made?

How is it broken down?

Definition

Acetyl group is combined with choline by  choline acetyltransferase --> ACh

 

ACh is broken down into choline and acetate by acetylcholinesterase

Term

 

What happens in Myasthenia Gravis?

Definition

- antibodies are made against nicotinic ACh receptors in muscle

 

- treated with drugs that inhibit acetylcholinesterase

 

- characterized by muscle weakness - ptosis

 

 

Term
How does the vagus nerve slow down the heart?
Definition
ACh binds to muscarinic G-protein coupled receptors in the heart --> causes opening of K+ channels --> hyperpolarization --> decreases force and rate of contraction
Term
Where and how in the Muscarinic ACh G-protein coupled receptor does cholera toxin exert its effect?
Definition

Cholera binds to the alpha subunit of the Gs protein and inhibits the intrinsic GTPase activity.

This causes constituitively active G protein --> elevated cAMP levels in intestinal epithelium and resulting diarrhea.

Term

 

What is the rate-limiting step for catecholamine biosynthesis?

Definition

The conversion of tyrosine to DOPA by

Tyrosine Hydroxylase

- first step in the reaction

Term
What step in catecholamine metabolism is a target for inhibition by anti-psychotic drugs?
Definition

The inactivation of catecholamines by monoamine oxidase (MAO)

Dopamine --> DOPAL

Norepi & Epi --> DOPEGAL

Term
The degeneration of dopamine neurons in what part of the brain leads to Parkinsons?
Definition

substantia nigra

 

- etiology of degeneration unknown

Term

What do the following genes all share in common?

DJ-1

a-synuclein

UCHL1

Parkin

PINK1

Definition

 

mutations in these genes causes rare inherited form of Parkinson's disease

 

-associated with oxidative stress & oxidative damage

Term

What is the major excitatory neurotransmitter in the brain?

 

The major inhibitory one?

Definition

excitatory - glutamate

inhibitory - GABA

- GABA synthesized from glutamate via decarboxylation

Term
What amino acid is serotonin synthesized from?
Definition

Tryptophan

 

 

Trp  --->   5-Hydroxy-tryptophan --->  Serotonin

   hydroxylase                     Decarboxylase

Term
Cleavage of amyloid precsursor proteins (APPs) by which secretase enzyme(s) generates toxic Ab peptide accumulations?
Definition

b-secretase and g-secretase generate Ab peptide

 

- thought to cause Alzheimer Disease

- cleavage by a-secretase does not produce Ab peptide

 

 

Term
What blood clotting factors makeup the intrinsic pathway? What is the order of their cleavage? Which one(s) are cleaved by kininogen and kallikrein?
Definition

XII ---> XIIa (cleaved by kininogen & kallikrein)

XI ---> XIa

IX ---> IXa

X ---> Xa

 

(note order: 12, 11, 9, 10)

Term
What factors make up the Extrinsinc blood clotting pathway?
Definition
VIIa and X (tissue factor)
Term

What role does Vitamin K play in blood clotting?

 

What drug inhibits it?

Definition

Vitamin K allows Prothrombin ----> Thrombin

By adding g-carboxy group to a glutamate in Prothrombin,  Ca++ can bind.

Vit K also adds a g-carboxy group to factors IX, X, and VII. 

Coumadin (Warfarin, Dicoumarol) inhibits Vit K.

Term
Thrombin is homologous to Trypsin. How does it change fibrinogen to fibrin?
Definition
Thrombin hydrolyzes Fibrinogen at its arginine/glycine residues. The A and B parts of the 3 chains are released, enabling the a, b, g parts to aggregate (x2) = fibrin.
Term

Why would heparin be given to a heart attack patient?

 

What type of heterpolysaccharide+protein molecule is heparin?

Definition

Heparin enhances Antithrombin III activity, preventing blood clot formation.

 

It is a glycosaminoglycan.

Term
What part of TPA (tissue type plasminogen activator) is responsible for activation of plasminogen into plasmin?
Definition

Serine Protease

 

- activates plasmin which lyses blood clot

Term
Would acetylation of chromatin histones allow for more or less transcription?
Definition

Acetylation = decompacted = more transcription

 

deacetylation = tightly wound = less transcription

Term

For transcription of nuclear DNA which nucleic acid sequence(s) correspond to "start"? To "stop"?

 

Which corresponds to "stop" for mtDNA?

Definition

Nuclear:            Start codon: AUG 

Stop codons: UAA, UGA, UAG

 

mtDNA:                Stop: AGA

Term

What codon codes for methionine in nuclear DNA?

 

In mtDNA?

Definition

Nuclear DNA Met: AUG

 

mtDNA Met: AUA

Term
Which type of point mutation in an mRNA chain can result in synthesis of the same protein as the non-mutated sequence?
Definition

A Silent Mutation

 

ex. if UCA (serine) was mutated to UCU (also serine)

- depends on the redundancy (degeneracy) of the code

- lengths of mutant proteins are unchanged

Term

Which type of mRNA point mutation always results in a shorter mutant protein?

 

Which type always results in a longer protein?

Definition

Shorter:          Nonsense mutation 

- mutation results in termination codon

(UAA, UGA, UAG)

 

Longer:           Supressor mutation

- mutation results in suppression of termination

Term
What type of point mutation is responsible for sickle cell anemia?
Definition

a Missense Mutation

 

GAG --> GUG

(Glu --> Val)

 

- affects the Hemoglobin Beta chain

Term

What sized subunits are in Prokaryotic ribosomes?

 

Eukaryotic ribosomes?

Definition

Prokaryotic: 30, 50, 70

 

Eukaryotic: 40, 60, 80

Term

True or False:

 

Eukaryotic mRNA is polycistronic, has a poly A tail, and a 7-methyl G noncoding cap.

Definition

False

 

- eukaryotic mRNA is monocistronic

Term
What is the rate limiting reaction in porphyrin synthesis?
Definition

the first reaction, catalyzed by 

5-aminolevulinate synthase:

 

Glycine + Succinyl CoA --> ALA + CO2 + CoA

 

- pyridoxal phosphate is required coenzyme

Term
What 2 enzymes of heme/porphyrin synthesis are sensitive to lead poisoning?
Definition

Ferrochelatase

- the last step, leading to the formation of heme, where Fe2+ is added to Protoporphyrin IX

 

ALA dehydrase

- the second step, resulting in formation of  porphobilinogen

Term
What enzyme in porphyrin synthesis does hemin inhibit?
Definition

5-aminolevulinate synthase

aka

ALA synthase

 

- this enzyme is catalyzes the first and rate-limitng reaction: formation of ALA from Succinyl CoA and Glycine in the mitochondria

Term
What enzyme deficiency leads to Acute Intermittent Porphyria?
Definition

deficiency of Uroporphyrinogen I synthetase

- AIP patients are not light-sensitive (does not affect skin)

- can result in urine that turns blue/black on standing

Term
What common feature of porphyrias leads to an increase in porphyrin/heme synthesis  intermediates?
Definition

Decreased production of heme = increased ALA Synthase

 

(since hemin product is feedback inhibitor of this enzyme, its absence causes increased ALA synthase and enzyme activity, leading to buildup of intermediates)

Term

What is the most common Porphyria?

 

What enzyme deficiency causes it?

Definition

Porphyria Cutanea Tarda

 

-lack of Uroporphyrinogen Decarboxylase

 

-patients are photosensitive

Term
In addition to inhibitive feedback to ALA synthase, how does hemin control the Heme/globin balance?
Definition

Hemin activates the synthesis of globin peptide

- increses globin while decreasing heme

Term

What is Hemolytic (prehepatic) jaundice?

 

Definition

Hemolytic (prehepatic) jaundice: production of bilirubin exceeds liver's capacity to conjugate it w/ glucuronic acid for excretion --> unconjugated bilirubin is elevated in the blood.

Hemolytic anemia (caused by massive lysis of red blood cells, as in Sickle Cell), can lead to buildup of bilirubin, causing jaundice.

Term
What hepatic enzyme catalyzes the conjugation of UDP-glucuronic acid with bilirubin to make Bilirubin digluconuride?
Definition

Bilirubin glucuronyl-transferase

 

-increases solubility of bilirubin

Term
What reactions of heme degradation require NAPDH?
Definition

Heme (+ 02, NADPH + H+) -----------> Biliverdin

                     Heme oxygenase

Biliverdin (+ NADPH + H+) -----------> Bilirubin

                       Biliverdin reductase

Term
Name two factors that decrease hemoglobin's affinity for Oxygen.
Definition

decrease in blood pH (Bohr effect)

 

increase in blood levels of 2,3 BPG (high altitude)

Term

True or False:

O2, CO2, CO, and glucose can all bind to hemoglobin

Definition

 True

 

O2: higher affinity when Hb in relaxed state

CO2: binds at tissues, transported as NHCOO-

CO: poison, 200x higher affinity than O2

& prevents O2 release

glucose: HbA1c levels diagnostic for diabetics

Term
What part(s) of the hemoglobin molecule are affected by thalassemias?
Definition

Hereditary defects in synthesis of either a or b chains

 

- common in Mediterraneans

- b defects more common in U.S.

Term
What structure variation characterizes fetal vs. adult hemoglobin?
Definition
g chain in fetal Hb replaced after birth by b chain
Term

Which usually contains more protein than carbohydrate: proteoglycans or glycoproteins?

 

Which contains more carbohydrate?

Definition

Glycoproteins: usually more protein

 

Proteoglycans: more carbohydrate

Term

List 3 properties of Glycosaminoglycans (mucopolysaccharides).

 

Definition

1. N-containing

2. Polyanionic

(due to carboxyl-containing sugars [except Keratan sulfate] and/or sulfate groups)

3. Repeating disaccharide motif on long polysaccharide chain

Term
List 6 glycosaminoglycans
Definition

Hyaluronic acid

Heparin

Heparin sulfate

Keratan sulfate

Chondroitin sulfate

Dermatan sulfate

Term
The slipperiness of mucous, as well as the resilience of both synovial fluid and vitreous humor of the eye, are all due to their common component of polyanionic heteropolysaccharide chains. These chains have the ability to bind large amounts of water, and are known as ____________.
Definition

glycosaminoglycans

(GAGS)

 

- all glycosaminoglycans except hyaluronic acid are found covalently attached to protein, forming a "bottle brush" proteoglycan monomer.

Term
Scurvy is a collagen disorder relating to diet. Characterize 2 genetically-based collagen disorders.
Definition

Osteogenesis Imperfecta (OI) aka "brittle bone disease"

- point mutation in COL1A1 or COL1A2 results in switching of Gly --> prevent folding to triple helix

- severity: II>III>IV>I

Ehlers-Danlos Syndrome (EDS)

- a collection of defects including skin and joint hypermobility, bruising, scoliosis

Term

Which amino acids make up collagen's primary structure?

 

 

Definition

Gly-X-Y

 

Glycine at every 3rd position,

 X is often proline and

Y is usually hydroxyproline or hydroxylysine

Term

What type of collagen is found in intervertebral discs, cartilage, and vitreous body?

 

Which type is found in fetal skin?

 

Which type is found in skin and bone, tendon, blood vessels, and cornea?

Definition

Type II - cartilage, etc.

 

Type III - fetal skin

 

Type I - skin and bone, etc.

 

(Type IV in basement membrane)

Term
How may collagen genes are there and where are they located?
Definition
I don't know exactly- but there are a lot and they're scattered all over the genome!
Term
Vitamin C is required to prevent Scurvy, a defective collagen disease. What is Vitamin C's normal role in collagen synthesis?
Definition
Vitamin C is a reducing agent that, along with Fe2+ as a cofactor and O2, is required for the hydroxylation of pro-a-chain proline and lysine residues, forming hydroxyproline and hydroxylysine. These hydroxylations occur in the RER, and are catalyzed by prolyl hydroxylase and lysyl hydroxylase. Withough hydroxylation, collagen fibers cannot be cross-linked, decreasing tensile strength.
Term

True or False:

Like collagen, elastin is rich in hydroxyproline and hydroxylysine residues.

Definition

False

 

Elastin contains proline and lysine, but little hydroxyproline and no hydroxylysine. Also rich in nonpolar aa's Gly, Ala, and Val.

Term

In what fibrous protein are desmosine cross-links found?

 

What are they?

 

What do they do for the macro-stucture of the protein?

Definition

-Desmosine cross-links found in elastin.

 

-Consist of 3 allysine chains + 1 lysyl side chain

 

-Gives elastin its elasticity - makes it an interconnected rubber network

Term
Mutations in FBN1 on chromosome 15 are linked to what autosomal dominant disease?
Definition

Marfan syndrome

- FBN1 codes for fibrillin

 

Term

A person with which of the following oncogenes is most likely to develop cancer?

 

A. myc

B. ras

C. myc + ras

Definition

C. myc + ras

 

 

-there is cooperativity of oncogenes - a single mutation will not likely cause cancer

Term
c-src is a proto-oncogene. Most proto-oncogene products participate in cellular growth-controlling pathways. What is the normal cellular product of c-src?
Definition

protein tyrosine kinase

 

v-src (v=viral) is a constituitively active mutant of c-src

Term

What do chromosomes look like during mitosis?

 

During G1?

 

during interphase?

Definition

mitosis - condensed "X"

 

G1 - threadlike

 

Interphase - occupy "territories" only visible by staining

Term
The opposite charges of DNA and histone proteins allow them to be tightly bound together into chromatin. What gives each one its specific charge?
Definition

- DNA is highly acidic (has a - charge) due to the phosphodiester bonds linking the nucleotides (PO4-)

 

- Histone proteins are basic (have a + charge) due to their basic residues of histidine, lysine, and arginine

Term

 

 

What effect does methylation of DNA have on transcription?

Definition

 

 

 

Methylation of DNA represses transcription

Term

 

What effects do acetylatioin and phosphorylation of histones have on transcription?

Definition

 

Both acetylation and phosphorylation of histones activate transcription.

Term

 

 What are three ways that immune cell chromosomes differ from those of other cells?

(Characteristics that ultimately make them great for producing antibodies, but bad for cloning)

Definition

 

-Combinatorial joining of gene segments

 

-Imprecise joining of segments (junctional diversification)

 

-Somatic hypermutation

Term

True or False:

 

Telomerase activity is often deactivated in cancer.

Definition

 

False

 

It is often activated in cancers.

Telomerase is required to keep telomeres large and robust.

Term

 

What structure in the chromosome holds sister chromatids together and allows for attachment of the mitotic spindle during mitosis?

Definition

 

Centromere

Term

 

 

Describe the anatomy of a nucleosome.

Definition

 

A nucleosome consists of double-stranded helical DNA wound around a core of 8 histone proteins (H2A, H2B, H3, H4 x 2), forming "beads on a string". The beads are linked together by H1 histone linker proteins.

Term

 

What are HATs and HDACs?

Definition

HATs: Histone acetylases

 

HDACs: Histone deacytylases

-these are major chemotherapeutic targets

Term
Are most of the proteins found in mitochondria encoded by nuclear DNA or  mitochondrial DNA?
Definition

95% of the proteins found in the mitochondria are encoded by nDNA.

 

mtDNA codes for 13 proteins, which are synthesized in the mitochondrial matrix and function in electron transport.

Term
List 4 ways that mtDNA inheritance varies from Mendelian inheritance.
Definition

1. maternal inheritance

 

2. heteroplasmy (wild type mixed with mutant)

 

3. stochastic (random) segregation of mtDNA

 

4. threshold effect (of mutations)

Term

 

What 3 required proteins form the machinery for mtDNA replication ?

Definition

POLG - mtDNA polymerase g

 

mtSSB - mtDNA single stranded binding protein

 

Twinkle - mtDNA helicase

Term

 

What cells are the primary target of HIV?

Definition

CD4+ T-lymphocytes

 

 

- CD4 receptors bind HIV gp120

Term
AZT, 3TC, d4T, ddc, and ddl are all used to treat HIV by what mechanism?
Definition
They are all reverse transcriptase inhibitors. They bind competitively and inhibit chain elongation.
Term
A Western Blot test positive for p24 protein would indicate what?
Definition

 

HIV virus

 

(p24 is part of the virus capsule)

Term
What type of polymerase transcribes HIV proviral DNA?
Definition
Host Polymerase II transcribes proviral DNA in the nucleus.
Term

Where in the HIV RNA are the LTR regions located?

 

What do these regions do?

Definition

LTR (long terminal repeat) regions located at 5' and 3' ends.

 

-they are invariant, conserved domains

 

-serve as binding site for host transcription factors and allow for integration into host DNA

 

Term
Alpers' syndrome, Spinocerebellarataxia with epilepsy, and autosomal recessive Progressive external opthalmoplegia are all believed to be caused by mutations in which gene?
Definition

POLG

 

- coding for mitochondrial DNA polymerase

Term
Mutations in CCR2 and CCR5 wouldl likely have what effect on someone exposed to HIV virus?
Definition

 

Mutations in these CD4 co-receptors would likely decrease their chances of infection and/or increase their chances of survival.

Term
How are nascent polypeptides protected during translation?
Definition
40 to 50 residues of nascent chain are buried in the ribosome as they stretch out from the Peptidyl Transferase center during translation.
Term

Which part of tRNA accepts amino acids?

 

Which part talks to mRNA?

Definition

The 3' CCA end is where amino acids are esterified and attached to the growing protein.

 

The Anticodon portion of Loop 2 talks to mRNA.

Term
AUG can code for a start Methionine or an internal chain Methionine. What specialized tRNAs can tell the difference in prokaryotes and eukaryotes, respectively?
Definition

prokaryotes: FMet recognized by tRNA as START Met

 

eukaryotes: IMet recognized by tRNA as START Met

 

MetM is for internal Met in both euk & prok

Term
There are about 50 tRNAs and 61 codons. How is 50 tRNAs enough to recognize all 61 codons?
Definition

 

- there is redundancy in the code such that 61 codons only codes for 20 amino acids

 

- also, there is WOBBLE pairing in the 3rd position which allows 1 tRNA to recognize more than one amino acid

Term
What has to happen to an amino acid before it can be transferred to tRNA?
Definition

Aminacyl-tRNA synthetase catalyzes the reaction of the amino acid with ATP, which activates it for transfer to tRNA.

 

These steps allow for proofreading and ultimately ensure the fidelity of protein synthesis.

Term

What do Streptomycin, Tetracycline, Chloramphenicol, and Erythromycin all have in common?

How are they different?

Definition

-they are all antibiotics that target prokaryotic ribosomal subunits to inhibit protein synthesis

-Strep. and Tetra. target 30S, while Chlora. and Erythro. target 50S

-Strep. is Aminoglycoside,interferes w/ Initiation

-Tetracycline inhibits binding of AA-tRNA to A site

-Chlor. inhibits peptidyl transferase

-Erythro. is a Macrolide, inhibits translocation

Term
What is Puromycin? What does it do?
Definition

Puromycin is a toxin that inhibits protein synthesis in both prokaryotes and eukaryotes.

It imitates AA-tRNA and causes premature release of nascent polypeptides.

Term
How does a protein destined for secretion get targeted to the ER?
Definition

 

Protein secretion is cotranslational!

 

secretion sequence (60-70 residues) is recognized by SRP (signal recognition peptide) in the cytosol during translation. SRP controls elongation and targets protein for maturation in ER.

Term

When is trancription of lac operon mRNA high?

 

A. -lactose, -cAMP, +glucose

B. +lactose, -cAMP, +glucose

C. +lactose, +cAMP, -glucose

Definition

 

C. +lactose, +cAMP, -glucose

 

Lactose derepresses the constituitive repressor, allowing the polymerase to bind to the promotor region. cAMP needed for transcription.

Term
Which Eukaryotic RNA polymerase transcribes tRNA and 5S rRNA? Where is it found?
Definition

RNA Polymerase III

in the nucleoplasm

Term
What protein is used as a diagnostic predictor of atherosclerosis?
Definition

CRP

(c-reactive protein)

 

-produce by liver in response to disease, trauma

-marker of systemic inflammation

Term

 

Blue sclera is a sign of what disease?

Definition

 

OI

(osteogenesis imperfecta)

Term
Which enzyme is essential for cross-linking of collagen fibers?
Definition
lysyl oxidase oxidatively deaminates some of the lysyl and hydroxylysyl residues so they can cross-link
Term

 

Which residue(s) are selectively glycosylated in procollagen?

Definition

 

 

Lysine , with glucose and galactose

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