Uric acid degradation

The presence of uricase assists the uric acid to be hydrolysed, and the end product of purine degradation is completed with the addition of uricase. 

Human tissues can synthesize purines and pyrimidines from amphibolic intermediates. Ingested nucleic acids and nucleotides, which therefore are dietarily nonessential, are degraded in the intestinal tract to mononucleotides, which may be absorbed or converted to purine and pyrimidine bases. The purine bases are then oxidized to uric acid, which may be absorbed and excreted in the urine. While little or no dietary purine or pyrimidine is incorporated into tissue nucleic acids, injected compounds are incorporated. The incorporation of injected [ H] thymidine into newly synthesized DNA thus is used to measure the rate of DNA synthesis. 

Figure 34-8. Formation of uric acid from purine nucleosides byway of the purine bases hypoxanthine, xanthine, and guanine. Purine deoxyribonucleosides are degraded by the same catabolic pathwayand enzymes,all of which existin the mucosa of the mammalian gastrointestinal tract.

Rouf M A, RF Lomprey (1968) Degradation of uric acid by certain aerobic bacteria. J Bacteriol 96 617-622. 

Durre P, JR Andreesen (1982) Anaerobic degradation of uric acid via pyrimidine derivatives by selenium-starved cells of Clostridiumpurinolyticum. Arch Microbiol 131 255-260. 

Demonstration of the anaerobic degradation of purines belongs to the golden age of microbiology and was appropriately discovered in Beijerinck s laboratory in Delft. Liebert (1909) obtained a pure culture of an organism that was able to grow anaerobically with 2,6,8-trihydroxypurine (uric acid). 

FIGURE 10.30 Alternative aerobic degradation of uric acid. 

Gout is caused by an abnormality in uric acid metabolism. Uric acid is a waste product of the breakdown of purines contained in the DNA of degraded body cells and dietary protein. Uric acid is water soluble and excreted primarily by the kidneys, although some is broken down by colonic bacteria and excreted via the gastrointestinal tract. 

Uric acid is one of the principal products of purine metabolism in man 12 13). However, in many other organisms further oxidative degradation of the purine molecule occurs. One of the most important enzymes involved in uric acid oxidation is uricase, which has been studied to some extent in vitro. 

Antioxidant enzymes also protect against free radical-mediated DNA degradation. For example, SOD and catalase as well as PARS inhibitors suppressed alloxan- and streptozotocin-induced islet DNA strand breaks [122], Uric acid inhibited single-strand DNA breaks induced... 

Another early genetic disease for correction by gene therapy was SCID. One form of this disease is caused by a lack of adenosine deaminase (ADA) activity. ADA is an enzyme that plays a central role in the degradation of purine nucleosides (it catalyses the removal of ammonia from adenosine, forming inosine, which, in turn, is usually eventually converted to uric acid). This leads to T- and B-lymphocyte dysfunction. Lack of an effective immune system means that SCID sufferers must be kept in an essentially sterile environment. 

In humans, uric acid is the end product of the degradation of purines. It serves no known physiologic purpose and is regarded as a waste product. The size of the urate pool is increased severalfold in individuals with gout. This excess accumulation may result from either overproduction or underexcretion. 

About two-thirds of the uric acid produced each day is excreted in the urine. The remainder is eliminated through the GI tract after enzymatic degradation by colonic bacteria. A decline in the urinary excretion of uric acid to a level below the rate of production leads to hyperuricemia and an increased miscible pool of sodium urate. 

Hyperuricemia predisposing to gout. Decreased Pj causes increased AMP, which is degraded to uric acid. Lactate slows uric acid excretion in the kidney. 

Figure 10.8 A summary of the reactions involved in the degradation of nucleic acid, nucleotides, nucleosides and purine and pyn midine bases. Nucleic add is hydrolysed by nucleases to form nucleotides, which are hydrolysed to nucleosides. The latter are split into ribose 1-phosphate and a base. The purine bases are converted to uric acid and ammonia. Uric acid is excreted. The pyrimidine bases are converted to 3-carbon intermediates (malo-nate semialdehyde and methylmalonate semialdehyde). The nitrogen is released as ammonia or used to convert oxoglutarate to glutamate.

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