Purine, Pyrimidine, Nucleotide Metabolism 1 & 2 Flashcards
1
Q
Key elements of purine structure
A
- Base: double ring
- Sugar: phosphorylated (nucleotide) or not phosphorylated (nucleoside)
2
Q
Examples of purines
A
- Guanine (G)
- DNA or RNA
- Adenine (A)
- DNA or RNA
3
Q
Key elements of pyrimidine structure
A
- Base: single ring
- Sugar: phosphorylated (nucleotide) or not phosphorylated (nucleoside)
4
Q
Examples of pyrimidines
A
- Uracil (U)
- RNA
- Thymine (T)
- DNA
- Cytosine (C)
- DNA or RNA
5
Q
Purine biosynthesis: source of carbons, products, key intermediates, key steps
A
- 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
Q
Pyrimidine biosynthesis: source of carbons, products, key intermediates, key steps
A
- 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
Q
Regulation of key steps in purine biosynthesis
A
- 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
Q
Regulation of key steps in pyrimidine biosynthesis
A
- 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
- Different than carbamoyl phosphate synthetase I:
9
Q
Gout
A
- 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
Q
SCID
A
- 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
Q
Lesch-Nyhan Syndrome
A
- 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
Q
Purine breakdown
A
- 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
Q
Pyrimidine breakdown
A
- 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
Q
Inhibition of nucleotide synthesis by drugs (and examples of these drugs)
A
- 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
Q
Methotrexate and 5-fluorouracil
A
- Target thymidylate synthase/folate metabolism cycle
- Anti-cancer
