Effect of Cystine on the Metabolism of Methionine in Rats

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Abstract
The effect of cystine supplementation of a low methionine diet on the metabolism of methionine has been investigated in rats prefed either a 0.6% methionine (Met) or 0.3% Met + 0.51% cystine (Cys) diet for 10 days. Hepatic methionine adenosyltransferase activity was similar in both groups while cystathionine synthase activity was depressed by 34% to 47% in the group fed the diet containing cystine. Methionine metabolism was studied using L-amino acid diets labeled with L-[1-14C]-methionine. Recovery of label in expired CO2 over an 8-hour period was 21.7 ± 0.6, 15.6 ± 0.4, 25.7 ± 1.0, and 24.6 ± 1.2 for rats fed diets containing 0.3% Met + 0.5% threonine (Thr), 0.3% Met + 0.51% Cys + 0.5% Thr, 0.3% Met + 0.1% Thr, and 0.3% Met + 0.51% Cys + 0.1% Thr, respectively. Cystine supplementation of the diets containing limiting threonine (0.1%) had no effect on recovery of 14C whereas supplementation of the diets containing adequate threonine (0.5%) depressed (P < 0.005) methionine oxidation by 39%. The specific activity (dpm/mg per µCi absorbed) of muscle protein was 42 ± 2, 44 ± 2, 39 ± 2, and 40 ± 2 for the four groups listed above, respectively. The decrease in methionine oxidation and increase in muscle protein specific activity with cystine supplementation in rats fed diets first-limiting in sulfur amino acids, and not in rats fed diets first-limiting in threonine, suggests that the rate of methionine oxidation is regulated primarily by the utilization of methionine for protein synthesis. The activity of cystathionine synthase is clearly not ratelimiting for methionine oxidation under usual conditions.