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PKM Biochemistry > Nucleic Acid Metabolism and Genetics > Flashcards

Nucleic Acid Metabolism and Genetics Flashcards

1
Q

Sources of atoms in pyrimidine synthesis

A

Glutamine
Aspartic acid
CO2

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2
Q

Sources of atoms in purine synthesis

A 
Glutamine
Aspartic acid
CO2
Glycine
N10-formyltetrahydrofolate
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3
Q

Rate limiting step!

Purine metabolism

A

Synthesis of 5-phospho-b-D-ribosylamine

PRPP glutamyl amidotransferase

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4
Q

Parent nucleotide for purines

A

IMP

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5
Q

How does IMP produce AMP?

A
  1. IMP (adenylosuccinate synthase) > Adenylosuccinate (1 GTP consumed)
  2. Adenylosuccinate (adenylosuccinase) > AMP
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6
Q

How does IMP produce GMP?

A
  1. IMP (IMP dehydrogenase) > XMP

2. XMP (transamnidase) > GMP (1 ATP consumed)

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7
Q

Rate-limiting enzyme

Pyrimidine synthesis

A

Carbamoyl phosphate synthetase II

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8
Q

Of the enzymes in pyrimidine synthesis, this is the only one located inside the mitochondria.

A

Dihydroorotate reductase

Synthesis of orotic acid

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9
Q

Parent pyrimidine

A

Orotidine monophosphate

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10
Q

How does OMP give rise to UMP

A

OMP acted on OMP decarboxylase to yield UMP

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11
Q

Purine degradation generally leads to production of ___ while pyrimidine degradation generates ___.

A

Purine: Uric acid
Pyrimidine:
1. B-alanine (> Acetyl CoA)
2. B-aminoisobutyrate (> Succinyl CoA)

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12
Q

What are the actions of the following enzymes in nucleic acid metabolism?

  1. Adenosine deaminase
  2. Thymidylate synthase
  3. IMP dehydrogenase
  4. Xanthine oxidase
A
  1. Adenosine > Inosine
  2. dUMP > TMP
  3. IMP > XMP
  4. Hypoxanthine > Xanthine > Uric acid
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13
Q

Mycophenolate and 6-mercaptopurine inhibit which enzymes in purine metabolism.

A

Mycophenolate: IMP dehydrogenase

6-mercaptopurine: Adenylosuccinase, IMP dehydrogenase

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14
Q

What is the only enzyme in pyrimidine synthesis that requires folate?

A

dUMP > TMP by thymidylate synthase.
Enzyme converts N5,N10-methylene H4 folate into dihydrofolate. The regeneration of tetrahydrofolate requires dihydrofolate reductase.

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15
Q

How does methotrexate work?

A

Methotrexate is a dihydrofolate reductase inhibitor. Dihydrofolate reductase inhibitor ‘recycles’ tetrahydrofolate required in the action of thymidylate synthase in pyrimidine synthesis.

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16
Q

ISIPIN NG MABUTI.

Orotic aciduria may arise from deficiency in mitochondrial ornithine transcarbamoylase. How?

A

Ornithine transcarbamyolase catalyzes formation of citrulline from carbamoyl phosphate and ornithine. With deficiency, carbamoyl phosphate builds up, leaks out of mitochondria into the cytosol and gets used in pyrimidine synthesis (combines with Asp). Elevated pyrimidine levels are eventually degraded to orotic acid.

Same thing happens with mitochondrial dysfunction in Reye’s syndrome.

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17
Q

In gouty arthritis in which there is overproduction or purines. The defect usually involves this enzyme.

A

PRPP synthetase

Elevated Vmax, increased affinity for ribose-5-phosphate, resistance to feedback inhibition

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18
Q

How does fluorouracil work?

A

5-FU is converted into F-dUMP which binds (and inactivates) thymidylate synthase.

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19
Q

Most important structural form of DNA

A

B-DNA

10 residues per 360deg turn

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20
Q

The nucleosome is composed of how many histones.

A
  1. 2 each of H2A, H2B, H3, and H4.
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21
Q

Mitochondria contains how many % of cellular DNA.

A

1%

22
Q

Which proteins involved in DNA synthesis are described?

  1. Recognize origin of replication
  2. Maintain separation of the parental strands
  3. Removes supercoils
  4. Unwind the double helix
  5. Seals nicks between Okazaki fragments
  6. Removes RNA primer
  7. Catalyze chain elongation
A
  1. DNA A protein
  2. Single-stranded DNA-binding proteins
  3. DNA topoisomerase
  4. Helicase
  5. Ligase
  6. DNA pol I
  7. DNA pol III
23
Q

Mammalian DNA pol Quiz

  1. Leading strand synthesis
  2. Lagging strand synthesis
  3. Mitochondrial DNA synthesis
  4. DNA proofreading and repair
A
  1. delta (pol III in prokaryotes)
  2. alpha (pol 1)
  3. gamma
  4. epsilon (pol 2)
24
Q

Which of the following repair mechanisms is part of the physiologic process of Ig gene rearrangement?

A. Mismatch repair
B. Base excision repair
C. Nucleotide excision repair
D. Double-strand break repair

A

D

25
Q

Which 2 proteins are important in double-strand break repair?

A

Ku protein

DNA-dependent protein kinase

26
Q

All enzymes are proteins. T/F

A

False. Ribozymes are RNA enzymes.

27
Q

When the following bases undergo spontaneous deamination, they turn into ___.

  1. C
  2. A
  3. G
A
  1. U
  2. Hypoxanthine
  3. Xanthine
28
Q

Modifications of mRNA in eukaryotic cells.

tRNA?

A

mRNA:
Poly-A tail (3’-end)
7-methylguanosine (5’-end)

tRNA:
3’CCA sequence added

29
Q

Promoter sequences in prokaryotes

A
  1. Pribnow box (-10)

2. -35 sequence

30
Q

Promotor sequences in eukaryotes

A
  1. Hogness box
  2. CAAT
  3. GC box
31
Q

Which RNA polymerase synthesizes

  1. tRNA
  2. mRNA
  3. rRNA
A
  1. Pol III
  2. Pol II
  3. Pol I (large); Pol III (small)

ReMiT = 1,2,3

32
Q

Differentiate enhancer sequences and promoter sequences

A

Promoter sequences bind with general transcription factors to begin initiation.

Enhancer sequences bind with activator transcription factors to increase rate of initiation.

33
Q

Which facilitate removal of introns?

A

snRNAs

34
Q

How many codons code for amino acids?

A
  1. The other three are stop codons.
35
Q

Enzyme involved in ‘charging’ reaction of translation

A

Aminoacyl-tRNA synthetase

Uses ATP

36
Q

Splicing sites are lost through mutations in the following conditions:

A

Tay-Sach’s
Gaucher’s
b-Thalassemia

37
Q

Diseases characterized by triple repeat expansion

A

Huntington’s (CAG)
Myotonic dystrophy (CTG)
Friedrich’s Ataxia (GAA)
fraGile X syndrome (CGG)

38
Q

The gene encoding for huntingtin protein is located in which chromosome?

A

Chromosome 4

MNEMONIC: Hunting 4 food

39
Q

The genes involved in the following conditions are found in which chromosomes?

  1. Von Hippel Lindau
  2. Huntington
  3. Neurofibromatosis 1
  4. Neurofibromatosis 2
  5. Familial adenomatous polyposis
A 
1. Chromosome 3
(3 words in Von Hippel Lindau)
2. Chromosome 4
(Hunting 4 Food)
3. Chromosome 17
(17 letters in Von Recklinghausen)
4. Chromosome 22
5. Chromosome 5
(Polyp has 5 letters)
40
Q

Autosomal trisomies and chromosome involved

A

Down syndrome: Drinking age (21)
Edwards’ syndrome: Election age (18)
Patau’s syndrome: Puberty (13); Palate (cleft), holoProsencephaly, Polydactyly

41
Q

The smallest unit of gene expression

A

Cistron

42
Q

In mammalian mitochondria, what are the stop codons?

A

AGA

AGG

43
Q

Which property of the genetic code is described?

  1. Multiple codons must decode the same amino acid.
  2. Only a single amino acid is encoded by a particular codon.
A
  1. Degeneracy

2. Specificity (Unambiguous)

44
Q

How many tRNA species are there in the cytoplasmic translation system? in the mitochondria?

A

Cytoplasm: 31 tRNA
Mitochondria: 22 tRNA

45
Q

Types of temporal responses to regulatory signals
A. Increased gene expression dependent on the continuing presence of an inducing signal
B. Increased amount of gene expression that is transient even with continued signal
C. Increased expression that persists indefinitely even after signal termination

A

A. Type A
B. Type B
C. Type C

46
Q

Describe the MOA of:

  1. Tetracycline
  2. Chloramphenicol
  3. Puromycin
  4. Cycloheximide
  5. Aminoglycosides
  6. Macrolide and Clindamycin
A
  1. Prevents binding of aminoacyl-tRNAs on the A site
  2. Inhibits peptidyltransferase
  3. Structural analog tyrosinyl-tRNA; causes premature release of peptide once incorporated
  4. Affects only eukaryotes; inhibits peptidyltransferase in 60S
  5. Binds to 30s and distorts its structure
  6. Binds irreversibly to 50s, inhibiting translocation
47
Q

Describe the MOA of the diphtheria toxin?

A

Catalyzes the ADP ribosylation (and inactivation) of EF2 inhibiting formation of pre-initiation complex.

48
Q

What is the effect of the following on protein translation:

A. Histone acetylation
B. Methylation

A

A. Histone acetylation (on Lys) results in disruption of nucleosoma structure and ready access of TFs (increase translation)

B. Methylation (on deoxycytidine) results in decreased translation

49
Q

Identify which binding motif is utilized

  1. CRE binding protein, myc
  2. Steroid receptor family
  3. Homeo box proteins, Oct 1
A
  1. Leucine zipper
  2. Zinc finger
  3. Helix-turn-helix
50
Q

On which chromosome do you find the genes that are defective in:

  1. Marfan
  2. Angelman
  3. Prader-Willi
A

15!

Chromosome 15 has its own MAP.
Marfan
Angelman
Prader-Willi

PKM Biochemistry (8 decks)

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