Urinary excretion of N gamma-methylihistidine (3-methylihistidine): a tool to study metabolic responses in relation to nutrient and hormonal status in health and disease of man.

Some of the histidine residues of actin and myosin are methylated after synthesis of these contractile muscle proteins. During breakdown of muscle protein in the course of protein turnover, the product of methylation, N gamma-methylhistidine, is released and quantitatively excreted in the urine both of rat and of man. Since most of the N gamma-methylhistidine in the body occurs in muscle, the rate of its excretion becomes a convenient measure of muscle protein breakdown. Output per kilogram of body weight is highest in the infant, especially when related to creatinine, and is reduced in the elderly as a result of loss of muscle mass with aging. A diet deficient in protein causes the young rat to have a reduced output of methylhistidine (reduced rate of muscle protein breakdown) which increases again during repletion on an adequate diet. Fasting obese human subjects also show a progressive fall in output of this metabolite. Thyroidectomy in rats reduces N gamma-methylhistidine excretion, which is only restored by giving large doses of thyroxine. On the other hand, studies on growing rats show that adrenalectomy and moderate doses of cortecosterone have no appreciable effect on the N gamma-methylhistidine output, which is only elevated by steriod administered in amounts large enough to raise plasma corticosteroid levels several-fold. These various observations show that N gamma-methylhistidine provides a useful tool in the study of muscle protein metabolic responses under a variety of nutritional and hormonal circumstances in the intact human.