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Degradation of purine nucleotides was evaluated in different types of rat skeletal muscle during ischemic and non-ischemic contraction. Extensor digitorum longus (EDL, fast) and soleus (slow) muscles were stimulated electrically via the sciatic nerve (5 Hz, 10 min). Under non-ischemic condition, the concentrations of IMP, inosine, adenosine, and hypoxanthine increased in EDL muscles but not in soleus muscles during stimulation. Under ischemic condition, these metabolites increased in both EDL and soleus muscles and the changes in concentrations of IMP and inosine were greater in ischemic EDL muscles. The increase in inosine had a strong positive correlation with that in IMP in ischemic EDL and soleus muscles, but the ratio, Δinosine/ΔIMP was smaller in EDL muscles. The increase in adenosine under ischemic condition was not significantly different between the two muscles. These findings suggest that ischemia enhances overall degradation of purine nucleotides in contracting fast and slow muscles, and that although the degradation of adenine nucleotides to IMP is greater in fast muscles than in slow muscles, the relative degradation rate of IMP to inosine with respect to the intramuscular IMP concentration is rather smaller in fast muscles.

We studied two brothers with hereditary xanthinuria (xanthine oxidase deficiency) and their family members. The two brothers had extremely low concentrations of urate but markedly high concentrations of xanthine and hypoxanthine in plasma and urine. Xanthine oxidase activities were virtually absent in the duodenal mucosa. In their parents (presumed obligate heterozygotes), the activities of xanthine oxidase were about half that of normal subjects. Although plasma xanthine and hypoxanthine concentrations of the parents were normal, urinary xanthine and hypoxanthine excretions were significantly higher than those of normal subjects (xanthine, father 17.1 mg/g creatinine and mother 27.4 vs. normal controls 5.7 to 11.0; hypoxanthine, father 14.0 and mother 27.3 vs. controls 4.0 to 8.4). Similar changes in the metabolite concentrations were seen in at least 6 other relatives, suggesting they were heterozygotes. This study indicates that the presumed obligate heterozygotes of xanthine oxidase deficiency retained about half normal enzyme activities causing the partial metabolic blockage in vivo at this enzyme step.

Excess purine degradation in exercising muscle due to impaired glycolysis causes hyperuricemia in muscle glycogenoses (myogenic hyperuricemia). However, hyperuricemia has been seen more frequently in Type VII than in Type V. This study was designed to clarify a metabolic basis for the different frequency of hyperuricemia between the diseases. 5 patients (2 males, 3 females) with Type V and 4 (3 males, 1 female) with Type VII participated in the study. 1) In every patient, semi ischemic forearm exercise caused no increase in lactate but exaggerated increases in ammonia, inosine and hypoxanthine in cubital venous blood. The ammonia increase was not different between Type V and Type VII, but it was greater in male than female patients. 2) Semiischemic forearm exercise performed after glucagon injection showed that lactate production was induced by exercise in Type V but not in Type VII. 3) Saline or glucose solution was infused in a patient with Type V during exercise on a bicycle ergometer. With saline infusion, ammonia and hypoxanthine in systemic circulation increased greatly after exercise. Conversely, with glucose infusion there were no increases in these metabolites. These findings indicated that blood glucose can be available as metabolic fuel through muscle glycolysis in Type V but not in Type VII. Thus, muscle purine degradation may be accelerated more in Type VII than in Type V, leading to a higher frequency of hyperuricemia.