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SFM Exam 2 > Exam 2 Review > Flashcards

Exam 2 Review Flashcards

1
Q

How does diphtheria toxin inhibit eukaryotic translation?

A

inactivates GTP bound EF interfering with ribosome translocation

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2
Q

Which step in the TCA cycle forms GTP by substrate phosphorylation?

A

Succinyl CoA to succinate by succinate thiokinase (succinate synthetase)
also forms CoA

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3
Q

What is cystinuria?

A

Defective transport of dimeric cystine and dibasic AAs Arg, Lys and ornithine
formation of cystine crystals in kidney, renal colic, abdominal pain, kidney stones

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4
Q

What is ADA deficiency?

A

Second most common form of SCID
Leads to increased adenosine levels and thus increased dATP as well as decreased dNDP/NTP which impairs DNA synthesis and leads to a compromised immune system

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5
Q

What is gout?

A

Characterized by high levels of uric acid in the blood
Results in extremely painful deposits of Na rate in the joints
Diets rich in purines can trigger episodes
tx = allopurinol which inhibits xanthine oxidase

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6
Q

What regulates citrate synthase?

A

Activated by insulin, acetyl CoA an OAA

Inhibited by citrate, ATP, succinyl CoA and NADH

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8
Q

What is the chemiosmosis hypothesis?

A

Coupling of the transfer of e- with phosphorylation of ADP to form ATP

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9
Q

What is the signal sequence for mitochondrial proteins?

A

N terminal hydrophobic alpha helix

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10
Q

How does rotenone effect oxphos?

A

Inhibits complex I and prevents e- transfer to ubiquinone (coenzyme Q)

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11
Q

What is Lesch Nyann syndrome?

A

Defects in HGPRT in purine salvage pathway
Rare form of hyperuricemia leading to gout, urate kidney stones, poor muscle control, mental retardation and tendency for self mutilation

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12
Q

What is the signal sequence for membrane proteins?

A

N terminal apolar sequences

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13
Q

What activates isocitrate dehydrogenase?

A

ADP and Ca2+

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14
Q

What role does xanthine oxidase play in purine catabolism?

A

Hypoxanthine -> xanthine -> uric acid

Target for gout tx

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15
Q

What is the signal sequence for ER lumen proteins?

A

KDEL

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16
Q

What is the signal sequence for lysosomal proteins?

A

mannose 6 phosphate

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17
Q

Describe pyrimidine catabolism

A

Converted to glucogenic or ketogenic compounds
Uracil/cytosine –> Malonyl CoA (ketogenic)
Thymine –> methylmalonyl CoA or succinyl CoA (glucogenic)

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18
Q

Which aa can be used to form propionyl CoA which can then make succinyl CoA?

A

Threonine, methionine, isoleucine and valine

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19
Q

What is acyclovir?

A

Antiviral agent that undergoes phosphorylation by viral thymidine kinase conveerting it to acylco-dGMP
Acyclo-dGMP -> acyclo-dGTP which is incororpated into dividing viral cells and terminates replication
Used to tx sores related to chicken pox, shingles and HPV

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20
Q

How does tetracycline inhibit prokaryotic translation?

A

Binds to 30s su and blocks entry of aminoacyl-tRNA to ribosome impairing elongation

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21
Q

How does cyclohgeximide inhibit eukaryotic translation?

A

inhibits peptidyl transferase and impairs peptide bond formation

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23
Q

What is pyruvate carboxylase deficiency?

A

Mutations in pyruvate carboxylase gene causing more pyruvate to be converted to lactic acid (instead of OAA)
sx: appears after birth, seizures, muscle weakness, and uncontrolled muscle movements

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24
Q

Describe 2-oxoglutaric acid aciduria

A

sx: chronic metabolic acidosis, severe microcephaly, excretion of 2-oxoglutarate and fulmaric acid
Lethal w/in first 10 years of life

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24
Q

Describe the glycerophosphate shuttle

A

Present in skeletal muscle and the brain

Generates FADH2 in the IMM which then joins ETC at CoQ

25
Q

Describe the secretory pathway of protein sorting

A

For proteins destined for the ER, lysosome, plasma membrane, or for secretion
Translation begins on free ribosome and ends on ribosomes sent to the ER
Each protein has an ER targeting signal

26
Q

What is Hartnup disease?

A

Defective transport of non polar or neutral AA such as tryptophan
Manifests as failure to thrive, nystagmus, tremor, intermittent ataxia and photosensitivity

27
Q

Describe pyruvate dehydrogenase deficiency (neonatal lactic acidosis)

A

Defect in PDC at E1 which effects males more bc gene is on X chromosome
High serum pyruvate and lactate
Tx: vitamin B1, lipoic acid and biotin supplements

27
Q

Describe succinyl CoA synthetase (SCS) deficiency

A

Mutations in 2/3 of subunits for SCS in SUCLA2 and SUCLG1 genes
Deafness syndrome, dystonia, mild methylmalonic aciduria

28
Q

How does chloramphenicol inhibit prokaryotic translation?

A

Inhibits peptidyl transverse and impairs peptide bond formation

30
Q

What role does adenosine deaminase (ADA) play in purine catabolism?

A

Irreversible hydrolytic deamination of adenosine into inosine
Overproduction in RBC leads to hemolytic anemia
Underproduction associate with SCID

31
Q

How does streptomycin inhibit prokaryotic translation?

A

binds to 30s and interferes with binding of fmet-tRNA impairing initiation

31
Q

How do shiga toxin and ricin inhibit eukaryotic translation?

A

Bind to 60s and block entry of aminoacyl tRNA to ribosome

32
Q

What is the signal sequence for nucleus proteins?

A

KKKRK

34
Q

How do clindamycin and erythromycin inhibit prokaryotic translation?

A

Bind to 50s su blocking translocation of ribosome

35
Q

What occurs when transfer of e- is inhibited?

A

Decrease in proton pumping and proton gradient

Inhibition of ATP synthase

37
Q

Oxidation levels of purines

A

Adenosine > GMP and hypoxanthine > xanthine > uric acid (limits its solubility and plays a role in gout)

38
Q

Describe the malate aspartate shuttle

A

Present in heart, liver and kidneys

Forms NADH into the mito matrix which then enters ETC at complex I

39
Q

What do defects in the salvage pathway of purines lead to?

A

Excess guanine and hypoxanthine are shunted to form 6x normal levels of uric acid
Purine synthesis increases at levels 200x normal

40
Q

What is SCID?

A

X linked disorder in adaptive immunity

Characterized by failure to thrive, thrush, chronic diarrhea, and recurrent viral, fungal and bacterial infections

41
Q

What inhibits isocitrate dehydrogenase?

A

ATP and NADH

41
Q

What is the signal sequence for secretory proteins?

A

tryptophan rich

44
Q

What occurs in phosphatase deficiency?

A

PDC always phosphorylated/inactive form
Glucose made into lactate resulting in lactic acidosis
CNS mostly affected
Restrict alanine intake and recommended ketogenic diet

45
Q

Which abx is the only elongation inhibitor?

A

puromycin (causes premature chain termination in both pro and eukaryotes)

45
Q

What is methotrexate?

A

Cancer tx
Targets DHFR which converts dietary folate into tethrahydrofolate in the liver
Prevents oxidation of NADPH and inhibits DNA replication in rapidly dividing cells

46
Q

Which aa can form fumarate?

A

Phe. tyrosine and aspartate

47
Q

What is the signal sequence for peroxisome proteins?

A

C terminal SKL

48
Q

Which abx inhibit eukaryotic translation?

A

Shiga toxin, ricin, diphtheria toxin and cycloheximide

49
Q

Which abx are prokaryotic translation inhibitors?

A

Steptomycin, clindamycin, erythromycin, tetracycline and chloramphenicol

49
Q

What are sulfa drugs?

A

Antibacterial agents that competitively inhibit the bacterial enzyme that incorporates PABA into folate
Selectively disrupt DNA replication in bacteria (since humans acquire folate as a vitamin the diet)

49
Q

What is the benefit of depriving cells of GMP and dGTP?

A

Therapeutic intervention that targets IMP dehydrogenase
An immunosuppressant that disrupts DNA replication in B and T cells by depriving them of adequate GMP and dGTP
Prevents transplant rejection

50
Q

Describe the cytoplasm pathway of protein sorting

A

For proteins destine for the cytosol, mitochondria, nucleus and peroxisome
Protein synthesis starts and ends on free ribosomes

51
Q

What inhibits complex III?

A

Antimycin

52
Q

What is Cockayne syndrome?

A

Autosomal recessive mutation in ERCC6 and 8 of TCR TCR repair
Neurologic delay, premature gaining (progeria), hearing loss and eye abnormalities

53
Q

What is hereditary non-polyposis colorectal cancer?

A

Also known as Lynch syndrome
Mutation in MER complex gene
Accumulation of DNA damage leading to genomic instability and resulting in cancer

54
Q

What is an example of a nonsense mutation?

A

Beta thalassemias
Lack of production of B-globin protein due to nonsense mutation
Homozygous mutation of splice sites + nonsense mutations that introduce premature stop signals at codons

55
Q

What is an example of a frameshift mutation?

A

Cystic fibrosis
Most commonly caused by a delegation of 3 nts from the coding region —> loss of Phe in the CFTR protein
Protein doesnt fold properly, Cl channel doesnt function, result is thick and sticky mucus in lungs and pancreas

SFM Exam 2 (25 decks)

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