Myopathy and Glycine Amidinotransferase

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Two steps are involved in creatine biosynthesis. The first step is the reaction from glycine and arginine to guanidinoacetate which is catalyzed by glycine amidinotransferase. The second step is methylation of guanidinoacetate which is catalyzed by guanidinoacetate methyltransferase. The first step is inhibited onlyin vivo by creatine as the end product 1.3). Muscles contain creatine in spite of absence of these two enzymes, and myopathy is usually associated with creatinuria. Is the origin of urine creatine in myopathy the muscle creatine or the synthesized creatine? In urine of a woman with polymyositis, creatinuria appeared persistently even under restricted creatine in the diet. Hundred percent of creatine, orally loaded, was recovered in urine, but her clinical course was stationary. Therefore, creatinuria in this case may depend more on increase in the biosynthesis accompanying decrease in storage capacity than on destruction of muscle. Biosynthesis of creatine is the problem. It was studied, by using rat, by what factor glycine amidinotransferase was controled. The results were as follows: these treatments, such as fasting, feeding on protein free diet, or injections of hydrocortisone, of estrogen or of creatine, reduce the activity of transferase, whereas such treatments as feeding on creatine free diet, or injection of testosterone, induce the activity of transferase. But the animal, fed on some creatine containing diet, does not show the reduction in this enzyme activity by either estrogen or hydrocortisone. In this connection, of interest is the fact that the urinary creatine amounts in polymyositis, described above, increase by injection of testosterone, but no changes in urinary creatine appear by injection of estrogen. These findings may tell us that the rate of creatine biosynthesis in myopathy is increasing, and this fact results from disturbance of hormonal control on glycine amidinotransferase by creatine, derived from destruction of muscle, or from dietary creatine accompanying the reduction of storage capacity.
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Myopathy and Glycine Amidinotransferase

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