Purine, Pyrimidine, Nucleotide Metabolism 1 & 2 Flashcards Preview

DEMS: Unit IIb > Purine, Pyrimidine, Nucleotide Metabolism 1 & 2 > Flashcards

Flashcards in Purine, Pyrimidine, Nucleotide Metabolism 1 & 2 Deck (20)
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1

Key elements of purine structure 

  • Base: double ring
  • Sugar: phosphorylated (nucleotide) or not phosphorylated (nucleoside)

2

Examples of purines

  • Guanine (G)
    • DNA or RNA
  • Adenine (A)
    • DNA or RNA

3

Key elements of pyrimidine structure

  • Base: single ring
  • Sugar: phosphorylated (nucleotide) or not phosphorylated (nucleoside)

4

Examples of pyrimidines

  • Uracil (U)
    • RNA
  • Thymine (T)
    • DNA
  • Cytosine (C)
    • DNA or RNA

5

Purine biosynthesis: source of carbons, products, key intermediates, key steps

  • Source of carbons: variety of sources, including several amino acids and small molecule sources
  • Made by starting with ribose sugar then uilding base onto sugar, one step at a time
  • First base used in pathway: inosine mono-phosphate (IMP)
    • IMP then used to make GMP and AMP bases
  • Feedback loops: IMP, GMP, AMP inhibit enzymes acting early in pathway

6

Pyrimidine biosynthesis: source of carbons, products, key intermediates, key steps

  • Source of carbons: both amino acid and small molecule sources
  • Pyrimidine base ring made separately and then added to sugar (different from purine synthesis)
  • First nucleotide produced: uracil mono-phosphate (UMP)
  • To make cytosine: UMP --> UTP --> CTP by CTP synthase enyzme

7

Regulation of key steps in purine biosynthesis

  • Key regulated step: at the start 
    • PRPP and glutamine used by glutamine phosphoribosyl pyrophosphate amidotransferase to add first nitrogen
  • Secondary regulated step: conversion of ribose 5'-phosphate to PRPP

8

Regulation of key steps in pyrimidine biosynthesis

  • Key regulated step: carbamoyl phosphate synthetase II catalyzes first step in pyrimidine ring synthesis
    • Different than carbamoyl phosphate synthetase I:
      • In cytosol, activated by PRPP, inhibited by UTP

9

Gout

  • Caused by buildup of uric acid (result of purine degradation pathway) in blood
  • Can be caused by: 
    • Deficiencies of enzymes
    • Hyperactivities of enzymes
    • Risk factors: age, diet, etc.

10

SCID

  • Mutation in gene encoding adenosine deaminase
    • Mutated enzyme used in purine degradation pathway
  • Leads to buildup of dATP --> inhibits ribonucleotide reductase --> prevents enough dNTPs from being made
  • Rapidly proliferating cells (immune system!) affected

11

Lesch-Nyhan Syndrome

  • Caused by deficiency in one of primary enzymes in purine salvage pathway (HGPRT)
  • Leads to higher rates of de novo synthesis of purines
  • Patients may have gout symptoms, self-mutilating behavior, other severe mental disorders

12

Purine breakdown

  • First remove base from sugar --> free base (adenosine or guanine)
  • Free bases broken down --> uric acid
  • Uric acid excreted from body in urine
  • Failures in this pathway can lead to disease

13

Pyrimidine breakdown

  • First remove base ring from ribose sugar
  • Base ring then opened up (different from purine breakdown)
  • Breaking down of base ring --> molecules to be used in other pathways 
    • Succinyl-CoA, Malonyl-CoA, Acetyl-CoA
  • Products of pyrimidine metabolism are water-soluble --> do not cause problems like uric acid can

14

Inhibition of nucleotide synthesis by drugs (and examples of these drugs)

  • Drugs developed to target nucleotide synthesis and degradation, or to mimic nucleotides
  • Designed to treat gout, cancer, or viral infection
  • Examples:
    • Methotrexate and 5-fluorouracil
    • 6-mercaptopurine
    • Azidothymidine (AZT)
    • Cytosine arabinoside (araC)
    • Acyclovir (ACV)
    • Acivicin

15

Methotrexate and 5-fluorouracil
 

  • Target thymidylate synthase/folate metabolism cycle
  • Anti-cancer

16

6-mercaptopurine
 

  • Inhibits AMP synthesis
  • Anti-cancer

17

Azidothymidine (AZT)

  • Inhibits viral polymerase
  • Anti-HIV

18

Cytosine arabinoside (araC)

  • Targets DNA polymerase
  • Anti-leukemia

19

Acyclovir (ACV)

  • Targets viral DNA polymerase and reverse transcriptase
  • Anti-Herpes simplex virus

20

Acivicin

  • Gln analog
  • Inhibits nucleotide synthesis (mostly GMP)
  • Anti-cancer