Sulfur Amino Acids and Immunity

Methionine and cysteine are essential and conditionally essential amino acids, respectively. Both contain sulphur as part of their R group and are important nutritionally with regard immune function. Methionine can be converted in the body to cysteine via the intermediary homocysteine in the transulfation pathway, which involves the enzymes cystathionine β-synthase and cystathionine γ-lyase (both requiring pyridoxal phosphate as a cofactor). The cysteine produced via the transulfation pathway can be used for the formation of the tripeptide glutathione (GSH) or can be metabolised to taurine or sulfate. Alternatively homocysteine can be recycled to methionine via the remethylation pathway utilising the enzymes methionine synthetase (which requires methylcobalamin as a cofactor and folate as a methyl donor). The Km values for the transulfation pathway are two orders of magnitude larger than the transferase pathway, and so at low intracellular concentrations of methionine, remethylation via homocysteine is favoured over transulfation to cysteine.

When dietary sulphur containing amino acids are limited, methionine in cells is conserved via remethylation of homocysteine to methionine. However, when sulfur availability increases, flux down the transulfation pathway increases resulting in increased formation of GSH, taurine and sulfate. In addition, the enzyme used to incorporate cysteine into protein (L-cysteinyl-tRNA syntetase) has a Km less than one tenth of the value of the GSH rate limiting enzyme γ-glytamyl cysteine synthetase, or the taurine and sulfate pathway enzyme, cysteine dioxygenase. Because of this when dietary sulfur intakes are low, protein synthesis can preferentially occur while GSH, taurine and sulfate synthesis is curtailed. These pathway control mechanisms have important knock on effects for immunity, because both GSH and taurine are known to be important in the proper functioning of the immune system. Increasing sulfurous amino acid intake, as might occur with whey protein supplement, may therefore be beneficial to immunity.

Low dietary intakes of sulphur amino acids caused by low protein intakes lower GSH concentrations in cells and plasma. Glutathione is important in cellular antioxidant defence and immunity, and its synthesis is increased by administration of sulfur amino acids and some sulfur containing compounds. Glutathione produces negative feedback on γ-glutamyl cysteine synthetase, the rate-limiting enzyme in GSH synthesis. This means that GSH synthesis is driven by cellular demand for GSH. Studies investigating the effects of increased sulfur on GSH and immunity have often increased sulphur supply to cells via intakes of the sulfur containing precursor molecules N-acetyl cysteine (NAC) and L-2-oxothiazolidine-4-carboxylate (OTC), mainly because of stability problems with sulfur in its reduced form and its toxicity at high doses. Supplemental OTC is a substrate for 5-oxoprolinase which converts it to S-carboxy-L-cysteine which is rapidly metabolised to L-cysteine, intracellular. Supplemental NAC is rapidly deacylated intracellularly to yield L-cysteine.

Although taurine is an end product of methionine metabolism, it is known to play an important part in immune system function. Cats cannot synthesis taurine and deficiency impairs immunity, as it may also do in human premature infants. In particular, taurine deficiency may decrease lymphocyte numbers and impair the phagocytic properties necessary for bacterial defence. Taurine may interact with hypochlorous acid produced during the respiratory burst of macrophages producing taurine chloramine and have a pronounced immune modulatory effects. Taurine is the most abundant free nitrogenous compound in cells and is though to affect the stability of the cell because of its stabilising effects on membrane fluidity and calcium flux. Like GSH it also possesses antioxidant functions and may control the release of inflammatory cytokines. However, increases in physiological taurine concentrations above the normal range are not able to improve immunity.

RdB

Grimble, R. F. 2006. The effects of sulfur amino acid intake on immune function in humans. Journal of Nutrition. 136: 1660-1665

About Robert Barrington

Robert Barrington is a writer, nutritionist, lecturer and philosopher.
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