Fig. 1.
Scheme showing liver methionine metabolism. Methionine, an essential amino acid, enters the cell and is metabolized via the methionine cycle to AdoMet in a reaction catalyzed by methionine adenosyltransferase (MAT). Functional methyltransferases (MT) and glycine-N-methyltransferase (GNMT) use AdoMet as a methyl group donor and generate AdoHcy, which is hydrolyzed by the action of adenosylhomocysteine hydrolase (AHC) to adenosine and homocysteine. The latter is used in the methionine cycle via the action of methionine synthase (MS) or betaine homocysteinemethyltransferase (BHMT). Alternatively, homocysteine can be converted via the action of the transsulfuration pathway enzymes, cystathionine β-synthase (CBS) and γ-cystathionase (CSE), to cystathionine and cysteine, respectively. CBS and CSE are also involved in H2S biogenesis. Cysteine can be oxidized to either taurine or sulfate or converted to GSH via the actions of γ-glutamylcysteine ligase (GCL) and GSH synthetase (GS). The turnover of GSH occurs via the transmembrane GSH/cysteine cycle and is initiated by its export. Two membrane-bound enzymes, γ-glutamyltranspeptidase (GGT) and a dipetidase (DP), cleave GSH to its component amino acids. Cysteine is oxidized to cystine in the extracellular compartment and can be imported by the glutamate/cysteine antiporter, xC−.