Nucleotide Metabolism Flashcards
What are the three structures of a nucleotide?
Pentose sugar, nitrogenous base, phosphates
What are polymers of nucleotides?
Nucleic acids
What is a base + sugar?
nucleoside
What are the two purines?
adenine and guanine
What are the three pyrimidines?
thymine, cytosine, and uracil
What are some of the uses of nucleotides? (5)
- Energy currency
- Phosphate source
- Coenzymes
- Substrate activators
- 2nd messengers
What is an important intermediate in the biosynthesis of purines?
PRPP
PRPP is formed from ribose-5-phosphate. What enzyme is used? Activator? Inhibitor?
PRPP synthetase; inorganic phosphate; ADP
The base of what is built upon a molecule of PRPP?
A purine ring
Where do the carbons in a purine ring come from?
glycine, folate derivatives, and CO2
Where do the nitrogens in a purine ring come from?
glycine, aspartate, and glutamine
What is the first purine formed in the ten-step process?
IMP - inosine monophosphate
How many high energy bonds are required in purine synthesis?
6
AMP and GMP are formed from what?
IMP
What amino acid provides a nitrogen to IMP in the formation of adenosine?
aspartate
In the formation of guanosine, glutamine provides a nitrogen to what?
xanthosine
Where are the enzymes that construct the purine ring system?
cytosol, namely the liver, which secretes free bases and nucleosides
What are the first two steps of purine synthesis?
PRPP sythesis and amidotransferase
What is the committed step of purine synthesis?
2nd step - PRPP amidotransferase
What cells are reliant on purine recycling?
brain, lymphocytes, neutrophils
Purine rings are recycled by what?
re-attachment to PRPP
In purine recycling Adenine phosphoribosyl transferase forms what from adenine?
AMP
In purine recycling hypoxanthine-guanine phosphoribosyl transferase (HGPRT) recycles H and G to form what?
Hypoxanthine > IMP
Guanine > GMP
What are the original ring components of pyrimidines?
glutamine, aspartate, and CO2
What enzyme forms UMP?
CPS-II carbomoyl phosphate synthetase
Where is UMP formed?
Cytosol and mitochondria
What is required in the formation of CTP from UTP?
glutamine
Deoxyribonucleotides are formed by reduction of what?
ribonucleotide disphosphates
What is the product of purine breakdown?
Uric acid
What is the key enzyme in the degradation of purines and pyrimidines?
Xanthine oxidase
What are the cofactors in the degradation of purines and pyrimidines?
O2, molybdenum, iron, sulfur
Beta-alanine and beta-aminoisobutyrate are the final products of what?
pyrimidine degradation
What are used to treat neoplasms?
Inhibitors of nucleotide metabolism
We don’t store nucleotides, so what happens if we have extra?
They get degraded
What are the three inhibitors of nucleotide metabolism?
Structural analog, antifolates, glutamine antagonists
What is a folic acid analog?
methotrexate
Gout results from what?
Deposition of sodium urate crystals in the joints and kidneys
What is defective in gout? (2)
PRPP synthetase is abnormal in some cases; HGPRT may be partially deficient in others
In gout, leukocytes take up crystals and what happens next?
They rupture, releasing lysosomal enzymes which inflame and erode joints. Uric acid crystals in the kidney impair renal function
What blocks formation of uric acid crystals through suicide inhibition of xanthine oxidase?
Allopurinol
de novo purine synthesis is decreased by the reaction of what two things?
PRPP with allopurinol
What is an anti-inflammatory used to reat gout which inhibits leukocyte movement?
Colchicine
What inhibits organic ion transport? (gout)
Probenicid
What condition is associated with x-linked recessive, deficiency of HGPRT activity?
Lesch-Nyhan syndrome
In lesch-nyhan syndrome, intracellular levels of PRPP increase, IMP and GMP decrease. What does this lead to?
Increase in de novo purine synthesis
What are some of the symptoms of lesch-nyhan syndrome?
gout, hyperuricemia, urinary tract stones, mental retardation, self-mutilation, spasticity
PRPP cannot react with allopurinol, so in treating lesch-nyhan syndrome, de novo purine synthesis does not decrease. What is reduced? What is not reduced?
gout; mental symptoms
What is deficient in glycogen storage disease type I (von gierke’s)?
Glucose-6-phosphatase
What two things are increased in glycogen storage disease type I (von Gierke’s)?
ribose-5-phosphate and PRPP
In glycogen storage disease type I (von gierke’s) is de novo purine synthesis increased or decreased?
increased
What condition is associated with the following?:
- defective conversion of orotate or orotidine monophosphate to UMP
- reduced DNA and RNA synthesis results leading to sever anemia
- treatment with uridine can be effective
Orotic aciduria
