Met 2: Purine/Pyrimidine Flashcards

1
Q

Compare the structure of Purines and Pyrimidines

Classify the nitrogenous bases.

A
  • Purines: two rings, Adenine, Guanine
  • Pyrimidines: one ring, cytosine, thymine (only DNA), uracil (only RNA)
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2
Q

______ bases are built onto the ribose sugar

_______ bases are built by making the base first and then attaching ribose later

A

Purine bases are built onto the ribose sugar

Pyrimidine bases are built by making the base first and then attaching ribose later

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3
Q

AMP and GMP are produced from ____

A

AMP and GMP are produced from IMP

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4
Q

Name the intermediates leading up to AMP and GMP

A

G6P -> Ribose 5 Phosphate -> 5 PRPP -> IMP ->

AMP and GMP

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5
Q

Describe the first step in purine synthesis

A

Glucose 6 phosphate converted to ribose 5 phosphate in HMP shunt (by G6P dehydrogenase)

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6
Q

Describe the second step of purine synthesis.

What is the enzyme and its inputs

A

Ribose 5 phosphate converted to 5 PRPP

by PRPP synthase

Requires ATP and Mg

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7
Q

Describe the third step of purine synthesis.

What is the enzyme?

What are its inputs? (5)

A

5 PRPP converted to IMP

by G PRPP amidotransferase

Glycine, Glutamine, Aspartate donate NH3

THF, CO2 donate carbon

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8
Q

Describe regulation of IMP conversion into AMP and GMP (2)

A
  • Increased concentration of one nucleoside upregulates production of the other b/c
    • Conversion of IMP into GMP requires ATP
    • Conversion of IMP into AMP requires GTP
  • Both pathways also have negative feedback (GMP and AMP inhibit their own production)
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9
Q

What two main enzymes are regulated in purine synthesis?

A

PRPP Synthase

Glutamine PRPP Amidotransferase

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10
Q

How are PRPP synthase and Glutamine PRPP amidotransferase regulated?

A
  • PRPP synthase and glutamine PRPP amidotransferase are both regulated using negative feedback
  • They are inhibited by IMP, AMP, GMP (downstream products)
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11
Q

What enzyme in pyrimidine synthesis gets regulated?

What are its two inputs?

Name 2 allosteric regulators

A

Carbamoyl phosphate synthase 2

Inputs are CO2 and Glutamine

Activated by ATP, inhibited by UTP

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12
Q

Name the 6 intermediates in pyrimidine synthesis

A

Glutamine + CO2 -> Carbamoyl phosphate -> orotic acid -> UMP -> UTP -> CTP

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13
Q

What 3 substances provide the carbons for pyrimidine synthesis?

A

Glutamine, CO2, Aspartate

  • Glutamine and CO2 are inputs for CPS2
  • Aspartate comes in later
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14
Q

What enzyme converts UTP into CTP?

What are its inputs?

A

CTP Synthase

Inputs: UTP and ATP

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15
Q

CPS I and CPS II are found in which pathways?

In what location?

A

CPS I: Part of urea cycle, in mitochondria

CPS II: Part of pyrimidine synthesis, in cytosol

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16
Q

Compare the allosteric regulators of CPS I and CPS II

A

CPS I: activated by N acetyl glu

CPS II: activated by ATP, inhibited by UTP

17
Q

What enzyme converts RNA nucleotides into DNA nucleotides?

A

Ribonucleotide reductase

18
Q

Describe the regulation of ribonucleotide reductase

A
  • Activity site is inhibited by dATP (product) and activated by ATP (precursor)
  • Substrate specificity site determines which deoxynucleotide gets made
19
Q

How is dTMP made?

Name one cofactor

A

dTMP (thymidine DNA nucleotide) is made from dUMP by thymidilate synthase

THF needed to donate methyl group

20
Q

What are the 4 intermediates in purine breakdown?

A

Adenosine -> Inosine -> Hypoxanthine -> Uric Acid

21
Q

Describe the enzymes involved in purine breakdown

A
  1. Adenosine deaminase needed to convert adenosine into inosine
  2. Xanthine oxidase needed to convert hypoxanthine into uric acid
22
Q

What is the product of pyrimidine breakdown?

A

Pyrimidine breakdown products are inputs for TCA cycle (acetyl coA, malonyl coA, succinyl coA)

23
Q

Describe the purpose of the purine salvage pathway

A
  • Purines are normally built onto ribose rings
  • Purine salvage pathway allows us to take purine bases that are already made and put them back onto rings
24
Q

What enzyme is needed for purine salvage?

What does it do and what are its inputs?

A

by Hypoxanthine Guanine Phosphoribosyl Transferase (HGPRT)

Converts adenine, guanine into AMP, GMP

Requires PRPP

25
Q

How does adenosine deaminase deficiency cause SCID?

A
  • Without adenosine deaminase, can’t degrade adenosine into inosine
  • dATP builds up
  • This inhibits ribonucleotide reductase (produces DNA nucleotides from RNA nucleotides)
  • Damages cell proliferation