Sulfur amino acid metabolism and requirements

Abstract

The sulfur amino acids (SAA) are methionine and cysteine. Methionine is indispensable.1–5 It donates its sulfur atom to cysteine during the process of trans-sulfuration, making cysteine a dispensable amino acid.6 The carbon skeleton of cysteine, however, is donated by serine.6 Methionine is metabolized via three major metabolic pathways: transmethylation, remethylation, and trans-sulfuration. It serves as the major methyl group donor in vivo,7,8 while cysteine is the rate-limiting substrate for the synthesis of the antioxidant glutathione (GSH).9–11 Both amino acids are important for protein synthesis. The total sulfur amino acid (TSAA) requirement, when fulfilled by the provision of methionine, can be significantly reduced only by adding cysteine to the diet. This phenomenon has been firmly established in animals12–15 and in humans16–18; it is consistent across the lifespan, having been observed in neonates,5–20 children,21 and adults.17,18 In the present issue of this journal, F. Jahoor examines the role the availability of sulfur amino acids plays in severe childhood undernutrition.22 The present editorial complements that work by providing an overview of SAA metabolism and requirements. ### Methionine In healthy adults, the metabolism of methionine is regulated toward anabolism23 in the fed state, and methionine flux is increased relative to that observed in the fasted state. Feeding results in decreased methionine release from protein breakdown and increased transmethylation, trans-sulfuration, and remethylation. In the fasted state, methionine utilization for protein synthesis is increased relative to transmethylation, resulting in the conservation of methionine when SAA availability is low. When SAAs are absent from the diet of healthy adults,17 methionine is used preferentially for protein synthesis relative to transmethylation, confirming previous findings that methionine is conserved via protein synthesis when SAA …