Arthritis purine metabolism

Uric acid is the endproduct of purine metabolism in man. Uric acid has a lower solubility than its progenitor metabolites, hypoxanthine and xanthine. Impaired uric acid elimination and/or increased uric acid production result in hyperuricemia and increase the risk of gouty arthritis. At physiological pH, 99% of the uric acid molecules are actually in the form of the urate salt. A decrease in pH increases the fraction of uric acid molecules relative to urate molecules. Uric acid possesses lower solubility than urate. 

Gout A group of disorders of purine metabolism, manifested by various combinations of hyperuricemia recurrent acute inflammatory arthritis induced by crystals of monosodium urate monohydrate tophaceous deposits of monosodium urate monohydrate crystals in and around the joints of the extremities, which may lead to crippling destruction of joints and uric acid urolithiasis. 

Mechanism of Action An immunologic agent that antagonizes purine metabolism and inhibits DNA, protein, and RNA synthesis. Therapeutic Effect Suppresses cell-mediated hypersensitivities alters antibody production and immune response in transplant recipients reduces the severity of arthritis symptoms. 

Gout is a metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate in joints and cartilage. Uric acid renal calculi, tophi, and interstitial nephritis may also occur. Gout is usually associated with hyperuricemia, high serum levels of uric acid, a poorly soluble substance that is the major end product of purine metabolism. In most mammals, uricase converts uric acid to the more soluble allantoin this enzyme is absent in humans. While clinical gouty episodes are associated with hyperuricemia, most individuals with hyperuricemia may never develop a clinical event from urate crystal deposition. 

B21. Blumberg, B. S., Heredity of gout and hyperuricemia in gout and purine metabolism. Arthritis Rheumd. 8, 627-633 (1965). 

This condition is a rare X-linked disorder of purine metabolism that usually kills in early childhood it causes kidney stones, arthritis, spasticity and mental retardation... 

Gout is a metabolic disease in which there is a overproduction of purines. It is characterized by intermittent attacks of acute arthritis produced by the deposition of sodium urate crystals in the synovial tissue of joints. Drugs used for treating gout are allopurinol, probenecid, colchicine, and NSAIDs. 

Inosine pranobex is a synthetic product, also known as isoprinosine or inosine dimepranol acedobene, with antiviral properties that are assumed to be related to its effect on T cell-mediated immunity rather than to direct antiviral activity. It has been tried in a wide range of viral diseases and also in rheumatoid arthritis (1), multiple sclerosis (2), and alopecia (3). However, clinical trials have mostly shown only modest therapeutic benefit or none at all (1,4), and no specific adverse effects, except for an increase in serum uric acid concentrations (5), reflecting the metabolic pathways of purines (6). 

Several diseases result from defects in purine catabolic pathways. Gout, which is often characterized by high blood levels of uric acid and recurrent attacks of arthritis, is caused by several metabolic abnormalities (Special Interest Box 15.4). 

Evidence of purine overproduction in childhood has led to detection of superactive PRPP synthetases in 2 families which are of special interest for several reasons, First, the hemizygous affected males in these families show severe sensorineural deafness in addition to uric acid overproduction. Second, the mothers of these boys share both the metabolic and hearing abnormalities with their sons, and one of these women has had both acute gouty arthritis and uric acid urolithiasis. Finally, as discussed below, the functional derangement in the enzyme of one of the families is unusually marked with more severe metabolic consequences of PRPP synthetase superactivity which might explain the childhood clinical onset, the development of gout in the mother, and even the associated deafness. 

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