Oxypurines are precursors of uric acid and are important metabolic intermediates which regulate uric acid synthesis. The myogenic and hepatogenic mechanisms for the pathogenesis of hyperoxypurinemia associated with hyperuricemia in various type of glycogenosis were investigated in this study.
The myogenic mechanism was investigated in patients with glycogenosis types III, V and VII, mitochondrial myopathy (Kearns-Sayre syndrome), hypoparathyroidism and hypothyroidism. During/after bicycle-ergometer exercise, plasma and urinary concentrations of inosine and hypoxanthine increased markedly. The semiischemic forearm exercise test, demonstrated that inosine and hypoxanthine were produced through excess purine degradation in exercising muscles.
The hepatogenic mechanism was investigated in a patient with glycogenosis type I. During/after glucagon-loading test, the plasma inorganic phosphate concentration decreased, and plasma and urinary concentrations of both hypoxanthine and xanthine increased markedly. Continuous glycogen breakdown following glucagon injection together with impaired glucose -6-phosphate hydrolysis due to glucose-6-phosphatase deficiency is known to result in a decrease in inorganic phosphate concentration in the liver. The depletion of inorganic phosphate accelerates purine degradation in the liver through deinhibition of both 5'-nucleotidase and AMP deaminase. Thus, hyperoxypurinemia due to a myogenic mechanism occurs only after exercise, and the plasma xanthine concentration increases slightly, in contrast to a marked increase in plasma hypoxanthine. On the other hand, hyperoxypurinemia due to a hepatogenic mechanism is manifest when the plasma glucose level is low, and the increase in oxypurine concentrationis predominant in the xanthine rather than the hypoxanthine component.
