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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Methionine-Adequate Cysteine-Free Diet Does Not Limit Erythrocyte Glutathione Synthesis in Young Healthy Adult Men^1,2

³ Research Institute, Hospital for Sick Children, M5G 1X8 Toronto, Canada; ⁴ Department of Nutritional Sciences, and ⁵ Department of Paediatrics, University of Toronto, M5G 1X8 Toronto, Canada; ⁶ School of Dietetics and Human Nutrition, McGill University, H3A 2T5 Montreal, Canada; and ⁷ Department of Agriculture, Food and Nutritional Science, University of Alberta, T6G 2P5 Edmonton, Canada

^* To whom correspondence should be addressed. E-mail: paul.pencharz{at}sickkids.ca.

Most methods of determining amino acid (AA) requirements are based on endpoints that determine adequacy for protein synthesis. However, the sulfur AA (SAA) cysteine is believed to be the rate-limiting substrate for synthesis of the most abundant intracellular antioxidant, glutathione (GSH). Our objectives were to determine whether supplementation of cysteine in a diet containing adequate SAA for protein synthesis, as methionine, increased GSH synthesis by measuring the fractional and absolute synthesis rates, and if concentration of GSH changed in response to feeding 5 graded intakes of cysteine (0, 10, 20, 30, and 40 mg·kg^–1·d^–1) in a random order with a fixed methionine intake of 14 mg·kg^–1·d^–1 and a protein intake of 1 g·kg^–1·d^–1. Each subject received a multivitamin and choline supplement during the study. Four healthy adult men each underwent 5 isotope infusion studies of 7-h duration after a 2-d adaptation to the level of cysteine intake being studied on the isotope infusion day. The isotope used was [U-¹³C₂ –¹⁵N]glycine. Analyses included erythrocyte GSH synthesis rates and concentration and urinary sulfate excretion. The GSH synthesis rates and concentration, measured at a methionine intake of 14 mg·kg^–1·d^–1, did not change with increasing intakes of cysteine. Urinary sulfate excretion showed a significant positive relationship with cysteine intake (r = 0.92; P < 0.01). In conclusion, this study provides preliminary evidence that consumption of SAA adequate to meet the requirement for protein synthesis does not limit GSH synthesis in healthy adult men receiving an otherwise adequate diet.

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