Phosphofructokinase (PFK) plays a key role in glycolysis, and deficiency of the muscle isozyme of PFK (PFK-M)is a typical clinical entity presenting as myogenic hyperuricemia The control of glycolysis at the PFK step might hold a key to the purine degradation observed in exercising muscles in patients with myogenic hyperuricemia. Our purpose in this study was to clarify the physiological significance of alternative splicing events (type A/B/C and exon 11 skipping) in the human PFK-M gene. By RT-PCR method, we identified the tissue specific distribution of the alternative transcripts in human tissues. In addition to type C, type A and B mRNA were found to be exclusively expressed in skeletal muscle, in which exon skipping was rarely observed. Other human tissues including the liver, kidney, stomach, pancreas, placenta and reticulocytes, expressed only type C mRNA. Exon skipping was clearly evidented in all tissues expressing type C mRNA other than muscle. The secondary structure and the hydrophobic moment of the gene product with exon skipping were predicted and were compared with those of the non-skipping product. with exon skipping the critical conformational changes would occur with skipping of exon 11.
These results suggest that the alternative splicing events observed in PFK-M gene contribute to the tissue-specific regulation of PFK activity.

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Strenuous exercise is known to cause temporary exercise-induced hyperuricemia. In this study, we examined whether long term hyperuricemia is caused by continuous exercise in 11 male longdistance and marathon runners (age range,20-42 years) by measuring serum uric acid level before and after a one-month intensive training period (“October Run”).
The mean daily running distance during this month(23.9±2.5km)was about 2.5 times that during the previous month(9.4±2.0km). In the following month(November), the mean daily running distance decreased to 10.4±1.5km during the first 2 weeks and 9.1±1.8km druing the last 2 weeks. The energy intake during the intensive training period was about 1.2 times that before the periodd, but no increase in body weight was observed, suggesting that the balance between energy intake and energy expenditure was maintained.
The mean serum uric acid levels was 6.1±0.2mg/dl immediately before the training Period,5.6±0.2mg/dl immediately after the period,5.4±0.3mg/dl 2 weeks thereafter. and 5.3±0.4mg/dl 4 weeks thereafter. The serum uric acid level immediately after and 2 and weeks after the training period was significantly reduced (p≤0.05) compared with that before the period.
These findings suggest that the serum uric acid level is not increased by continuous vigorous exercise despite an increase in the energy intake if this increase is balanced with the energy expenditure and produces no weight gain.

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We studied uric acid metabolism in elderly patients, in order to determine the effect of decreased muscular exercise relative to purine metabolism. We also investigated by means of oral inosine loading wheter there was any defect either in the production or renal excretion of uric acid in each patient.
Seventy-eight patients(males 28,77.3±6.1years old and females 50,79.2±5.7 years old)were divided into three groups according to basic activity level in daily living; the first group was composed of 26 bedridden patients, the second of 14 who could only move and take care of themselves with instrumental supports, and the third of 38 who could maintain a voluntary life style. Each subject in the patient group was receiving medication for arteriosclerotic disease. However, most of these medication have no significant effects on urate metabolism in humans.
After ultrasonographic measurement of upper arm skinfold thickness, muscle volume (MV)was calculated according to Heymsfield et al. We carried out a 24-hr urate clearance study and oral inosine loading for three days in five bedridden patients. The mass of MV showed a significant negative correlation with the increase in age of the patient. Serum uric acid ( s-UA) levels were distributed among the patient group between 1.5 and 6.9mg/dl, and five females of the patient group showed levels below 2.0mg/dl. Urate output from the patient group was as low as 97.9±115.2. mg/day. There was a positive correlation between the mass of MV and s-UA levels in the patient group. S-UA levels, in the patients of the third group who were maintaining an active life style, were signifcantly higher than those of the bedridden patients. S-UA levels in the five patients of the first group increased signifcantly from 3.5±1.8 to 7.7±2.3mg/dl after oral inosine loading. Urate output and urate clearance also increased after loading, although there were no significant changes in creatinine clearance in these patients.
It is known that muscular exercise increases purine metabolism due to enhanced ATP consumption and results in hyperuricemia, and that hyperuricemia and gouty attacks are frequently found in most sportsmen. However, there are few studies concerning the decreased production of uric acid under decreased muscular exercise.
The present studies suggests that in elderly subjects the turn-over of purine metabolism is decreased, because of the reduction of muscle volume and muscular exercise, resulting in lower levels of serum uric acid and urate output in elderly patients. There was no impairment in the metabolic process from inosine to uric acid, nor in the renal excretory mechanism of uric acid.

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