# Catabolism Of Purines And Pyrimidines
Purines and pyrimidines are nonessential components in our diet, meaning humans can synthesize these nucleotides de novo using amphibolic intermediates. Let’s delve into the breakdown process of these crucial molecules.
Purine Catabolism: The Path to Uric Acid
The end product of purine (adenine and guanine) catabolism in humans is uric acid.
Uric acid, however, has low solubility. Here’s a simplified breakdown of the pathway:
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Nucleotides to Nucleosides: Purine nucleotides (AMP and GMP) are broken down by nucleotidases, removing the phosphate group and yielding adenosine or guanosine.
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Adenosine to Inosine to Hypoxanthine: Adenosine deaminase converts adenosine to inosine. Subsequently, purine nucleoside phosphorylase hydrolyzes inosine, producing hypoxanthine and ribose-1-phosphate.
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Hypoxanthine to Xanthine to Uric Acid: Xanthine oxidase oxidizes hypoxanthine to xanthine and then to uric acid. This process reduces molecular oxygen to H2O2 and O2, which catalase further breaks down.
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Guanosine to Guanine to Xanthine to Uric Acid: Phosphorylase enzymes cleave guanosine into guanine and ribose-1-phosphate. Guanase then removes guanine’s amino group, yielding xanthine, which xanthine oxidase converts to uric acid.
The Uric Acid Conundrum: Hyperuricemia and Gout
At physiological pH, uric acid exists as sodium urate in plasma. Elevated serum urate concentration, known as hyperuricemia, can lead to gout. Both urate and uric acid are relatively insoluble, readily precipitating out of solutions like urine or synovial fluid. This precipitation is the culprit behind gout. Normal blood serum uric acid levels range from 4-7 mg/100ml.
- β-alanine can serve as precursor of acetyl-CoA
Since end products of pyrimidine catabolism are highly water soluble, overproduction of
pyrimidine catabolites is rarely associated with clinically significant abnormalities
Orotic Aciduria
A hereditary disorder which can result from a defective enzyme in pyrimidine synthesis. A defect in the multifunctional enzyme UMP synthase that converts orotic acid to UMP
results in the excretion of orotic acid in the urine. UMP synthase is a multifunctional enzyme containing both orotate phosphoribosyltransferase and orotidylate decarboxylase activity (from de novo synthesis of pyrimidine).
There are 2 types of orotic academia:
- Type-I – deficiency of both enzymes, orotate phosphoribosyltransferase and orotidylate decarboxylase
- Type-II – only orotidylate decarboxylase is deficient
Deficiency of UMP and other pyrimidine nucleotides results in inhibition of DNA and RNA synthesis. This causes megaloblastic anemia and failure to thrive (growth retardation).
Reye’S Syndrome
Is a secondary orotic aciduria. May be due to inability of severely damaged mitochondria to utilize carbamoyl phosphate in the formation of urea. It may then be diverted for cytosolic overproduction of orotic acid.
