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step 2 > Molecular Biochemistry > Flashcards

Molecular Biochemistry Flashcards

1
Q

What 3 compounds are needed to begin de novo pyrimidine synthesis?

A
  1. Glutamine
  2. CO2
  3. ATP
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2
Q

How do the purine and pyrimidine de novo synthesis pathways differ in terms of their starting materials?

A 
Purine = Start with a sugar (PRPP) and add a base
Pyrimidine = Start with a base (orotic acid) and add a sugar (PRPP)
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3
Q

What is the rate limiting step of de novo pyrimidine synthesis?

A

Carbamoyl phosphate synthetase II converting Glutamine, CO2 and ATP to carbamoyl phosphate

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4
Q

What is carbamoyl phosphate converted to for pyrimidine synthesis? What is required for this conversion?

A

Orotic acid, needs aspartate

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5
Q

What is the defective enzyme in orotic acid uria? What is its normal function?

A

UMP synthase defeciency

Normally (orotic acid + PRPP) is converted to UMP by UMP synthase

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6
Q

What are the key features of orotic aciduria?

A
  • Orotic acid in urine without hyperammoniemia (indicating that it is not a urea cycle problem)
  • Failure to thrive
  • Megaloblastic anemia
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7
Q

How do you treat orotic aciduria?

A

Increase uridine in the diet

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8
Q

Once UMP is made what are the final steps in the pyrimidine synthesis pathway?

A

UMP –> UTP –>CTP
and
UMP–>UTP–>dUTP–>dUMP–>dTMP via deoxyribonucleotide reductase and thymidylate synthase

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9
Q

What enzyme does hydroxyurea inhibit?

A

Deoxyribonucleotide reductase, no UTP–>dUTP

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10
Q

What enzyme does 5FU inhibit?

A

Thymidylate synthase, no dUMP –>dTMP

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11
Q

What cofactor does thymidylate synthase require?

A

Tetrahydrofolate which is converted to dihydrofolate in the process of making dTMP

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12
Q

What are the starting blocks for making a purine?

A

PRPP + Glycine + Aspartate + Glutamine

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13
Q

What is the rate limiting step in de novo purine synthesis?

A

Glutamine PRPP Amidotransferase

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14
Q

What are the substrates for, cofactors of, and products of Glutamine PRPP Amidotransferase?

A

Substrates: PRPP (from Ribose-5-P) + glycine +glutamine +CO2
Cofactor: THF
Products: IMP

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15
Q

What is IMP converted to in the purine synthesis pathway? What enzyme is involved?

A

IMP –> GMP via IMP Dehydrogenase
and
IMP –> AMP

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16
Q

What is the first part of the purine salvage pathway?

A

GTP, IMP, and ATP are converted to guanosine, inosine and adenosine respectively

17
Q

In the purine salvage pathway, what is adenosine converted into? By what enzyme?

A

Inosine, adenosine deaminase

18
Q

What does adenosine deaminase deficiency lead to?

A

SCID, decreased T and B cells with no thymic shadow and the triad:

  1. Severe recurrent infections
  2. Chronic diarrhea
  3. Failure to thrive
19
Q

What is guanosine converted to in the purine salvage pathway?

A

Guanine

20
Q

What is hypoxanthine converted into in the purine salvage pathway?

A

Hypoxanthine

21
Q

What are guanine and hypoxanthine both converted to in the purine salvage pathway? What enzyme is involved?

A

Xanthine, enzyme = xanthine oxidase

22
Q

What is xanthine converted to in the purine salvage pathway? What enzyme is involved?

A

Uric acid, xanthine oxidase

23
Q

What is the role of HGPRT in the purine salvage pathway?

A

Enzyme that takes Guanine back to GMP and Hypoxanthine back to IMP

24
Q

What deficiency leads to Lesch-Nyhan syndrome and how does it present?

A

HGPRT Deficiency

  • No pruine salvage = Increased uric acid production
  • Gout + MR +Aggressive behavior +Involuntary movements
25
Q

What drugs are metabolized by xanthine oxidase?

A

Azothioprine and 6-MP

26
Q

What is the treatment for Lesch-Nyhan syndrome?

A

Allopurinol

27
Q

How is Lesch-Nyhan syndrome inherited?

A

XLR

28
Q

What kind of mutation leads to each of the following:

  1. Sickle cell disease
  2. Duchenne muscular dystrophy
A
  1. Missense

2. Frameshift

29
Q

What is defective in xeroderma pigmentosum?

A

Nucleoside excision repair

30
Q

What is defective in HNPCC(Lynch)?

A

Mismatch repair

31
Q

What is defective in ataxia telangiectasia?

A

Non-homologous end joining

32
Q

Promoter

A
  • Site where RNA polymerase and trans-factors bind
  • Upstream of gene
  • TATA or CAAT box
33
Q

Enhancer

A

Alters DNA expression by binding transcription factors

34
Q

Silencer

A

Where repressors bind

35
Q

Where are enhancers and silencers located relative to a gene?

A

Close, far or even inside (ANYWHERE)

36
Q

How many types of RNA polymerase exist in prokaryotes? Eukaryotes? What are there functions?

A 
Prokaryotes = 1, makes all 3 RNA types
Eukaryotes:
1. RNA Pol I = rRNA
2. RNA Pol II = mRNA
3. RNA Pol III = tRNA
37
Q

In what disease to antibodies do snRNPs prevent splicing.

A

SLE

38
Q

To which end of the tRNA does the amino acid bind? To what sequence on the tRNA? What type of bond is formed?

A

3’, CCA sequence, covalent

39
Q

What sequence on a tRNA molecule is necessary for the binding of the ribosome?

A

T-arm, thymine, pseudouridine, cytosine

step 2 (16 decks)

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