The urinary excretion of total N-τ-methylhistidine by the growing rat was measured to evaluate the effects of dietary protein and energy restriction on muscle protein turnover in vivo. 2. Young male rats (about 100 g initial wt.) were fed on one of three diets. Group I (controls) received an adequate 18% lactalbumin diet for 28 days, on which they sustained maximum growth. Group II (protein-depleted) was fed for 14 days on 0.5 lactalbumin diet, which caused loss of weight; this was followed by repletion for 14 days with the control diet. Group III (protein-energy restricted) received a 1% lactalbumin diet at one-half the food intake of group II for 14 days, and this was also followed by 14 days of repletion with the control diet. 3. The controls showed a progressive rise in the daily urinary output of N-τ-methylhistidine, which was proportionally slightly less rapid than the body-weight increase. 4. The protein-depleted group II showed a marked and progressive decrease in N-τ-methylhistidine excretion, which was proportionally greater than the fall in body weight; during repletion, N-τ-methylhistidine output rose in parallel with body-weight increase, but it did not reach the value attained by the control group. 5. Group III, restricted in both dietary protein and energy, showed an initial small increase in daily N-τ-methylhistidine output, which contrasted with the sharp loss of body weight during this period. After 11 days on this restricted diet, group III then underwent a decrease in N-τ-methylhistidine output, which persisted into the first 4 days of the repletion period, after which output of the methylated amino acid became the same as for group II. 6. Creatinine output, used as an additional metabolic measure of muscle metabolism, showed a fairly constant relationship to body weight in groups I and II during depletion and repletion. However, rats with protein-energy deficiency (group III) underwent a marked increase in output of creatinine per unit of body weight, which also persisited into the repletion period before it fell to more normal values relative to body weight. 7. Analysis of the N-τ-methylhistidine content of actin isolated from a group of protein-depleted rats revealed a small (5%) but significance (P less than 0.02) decrease relative to well-nourished controls. 8. Hence, the rate of muscle protein degradation, as indicated by changes in urinary N-τ-methylhistidine output, appears to respond sensitively and in opposite directions to insufficiency of protein of energy in the diet.

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