| Research Abstract |
Hyperuricemia or gout has been reported to develop in some patients with muscle glycogenosis. The aim of this study was to clarify altered muscle purine metabolism, its contribution to urate metabolism and ultimately a metabolic basis for the development of hyperuricemia in muscle energy diseases, including glycogenosis types III, V and VII.
1) Rat muscles were contracted tetanically by electrical stimulation via sciatic nerve. There were a marked decrease in ATP content and the corresponding ncreases in IMP, inosine and hypoxanthine in fast-muscles (EDL), despite no such changes in slow-muscles (soleus). The accelerated ATP degradation was realized in contracting slow-muscle by elimination of blood flow.
2) After semiischemic forearm exercise, ammonia, inosine and hypoxanthine levels in cubital venous blood increased greatly in patients with glycogenosis types III, V and VII, in contrast with the lack of increase in lactate levels. Marked increases in ammonia and hypoxanthine after semi
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ischemic forearm exercise were also observed in patients with idiopathic hypoparathyroidism.
3) After ergometric exercise, plasma levels of ammonia, inosine and hypoxanthine in systemic circulation increased greatly in patients with glycogenosis types III, V and VII, as did the plasma urate, which showed a delayed response. Urinary excretion of inosine, hypoxanthine and urate also increased markedlyafter exercise.
4) Hypoxanthine and urate concentrations were extremely high in plasma and urine of a patient with glycogenosis type VII. With bed rest alone, the plasma hypoxanthine levels returned to normal within a few hours, and the plasma urate concentration decreased from 18.6 mg/dl to 10.6 mg/dl within 48 hours. Similarly, the urinary excretion of these purine metabolites was recuced by bed rest.
Accelerated purine degradation occurred in exercising muscles of patients with glycogenosis types III, V and VII, resulting in excessive release of its degradative product, such as ammonia, inosine and hypoxanthine, into circulating blood. These purine metabolites subsequently serve as substrate for the synthesis of uric acid in liver, leading to hyperuricemia (myogenic hyperuricemia). Less
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