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doi:10.1016/j.amjmed.2015.11.032 Kosciuszek ND, Kalta D, Singh M, Savinova OV

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Transsulfuration pathway • Ability for the liver cell to convert methionine to cysteine is important since the liver is the major site of methionine catabolism and the major storage organ for GSH • It is absent or insignificant in other GSH-synthesizing systems • Markedly impaired or absent in the fetus and newborn infant, cirrhotic patients, and patients with homocystinemia • the Km of hepatic methionine adenosyltransferase for ATP is high (2 mM) • hypoxic depletion of ATP is more likely to affect GSH synthesis from methionine than cysteine Transsulfuration pathway • Methionine and homocysteine are readily interconvertible • The transsulfuration pathway converts methionine to cysteine, which is then converted to GSH via the GSH synthetic pathway • Methionine can also be resynthesized from homocysteine • The control appears to be exerted at the level of homocysteine: when methionine is needed, homocysteine is remethylated by methionine synthase or betaine-homocysteine methyltransferase