Disorders of Purine and Pyrimidine Metabolism
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Functions of Nucleotides
- - Nucleotides serve as carriers of activated intermediates in the synthesis of
- Carbohydrataes - e.g. UDP-glucose
- Lipids - e.g. CDP-choline
- Conjugated proteins – e.g. Helicase enzymes
- - Nucleotides also act as “second messengers”
- e.g. cyclic AMP
- - Nucleotides hold onto and transmit directed energy
- (i.e. ATP and GTP as “Energy Currency”)
T and U differ only in that Thimine................
Thimine has an additional (1 carbon) methyl group
How purine is degraded?
- Phosphodiesterase enzymes cleave oligosaccharides into mononucleotides
- Nucleotidase enzymes then remove the phosphate, giving nucleosides
- ............. is the “end product” of purine breakdown
- Formed primarily in...................
- Uric acid is the “end product” of purine breakdown
- Formed primarily in intestinal mucosal cells
- Uric acid is formed from..................
What happens when Uric Acid crystallizes?
- - It deposits and forms Gout- If it deposits in the Kidney form Kidney Stones
The vast majority of gout happens because of inadequate excretion
- 1- Defects in kidney function
- 2- Lactate acidosis (which could lower the pH of urine and cause more urate to become insoluble)
- 3- Environmental factors, or taking certain drugs
How you treat Gout?
1- Lessen the amount of inflammatio
n (i.e use steroids, NSAIDS)
- 2- Get rid of the excess uric acid
- a- Use Uricosuric Agents to increase renal excretion. -------Probenecid
- B- Use Allopuranol (a structural analog of hypoxanthine) to inhibit synthesis of Uric Acid
- 3- Make it more soluble
- ----Urate Oxidase – that converts Uric Acid into Allantoin
- ---Allantoin is five to ten times more soluble than uric acid, so renal excretion is more effective
The key regulated step in the pyrimidine synthesis is making of ----------------
There are 2 Carbamoyl Phosphate Synthesis
(CPS) enzymes (I and II).
CPS I contributes to synthesis.............
CPS II contributes to synthesis..............
- There are 2 Carbamoyl Phosphate Synthesis
- (CPS) enzymes (I and II).
- CPS I contributes to synthesis of urea;
- CPS II contributes to synthesis of pyrimidines
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