Figure 1

Homocysteine metabolism. (1) Activation of methionine (MET) by ATP in the presence of methionine S-adenosyl-transferase (EC 2.5.1.6). (2) S-adenosylmethionine (SAM) demethylation into S-adenosylhomocysteine (SAH) coupled with methylation of an acceptor R into RCH₃. (3) Alternative demethylation catalyzed by glycine N-methyltransferase (EC 2.1.1.20), which converts glycine (Gly) into sarcosine (CH₃Gly). (4) Hydrolysis of SAH into homocysteine (HCYS) and adenosine catalyzed by S-adenosylhomocysteine hydrolase (EC 3.3.1.1). (5) Condensation of serine (Ser) with HCYS to form cystathionine (CTT) through the action of vitamin B₆-derived pyridoxal-5′-phosphate–dependent cystathionine β-synthase (CBS) (EC 4.2.1.22). (6) Conversion of CTT into cysteine (CYS) and α-ketobutyrate catalyzed by pyridoxal-5′-phosphate–dependent γ-cystathionase (EC 4.4.1.1). (7) N⁵-methyltetrahydrofolate (5-methylTHF) demethylation into THF and HCYS remethylation into MET by methionine synthase (EC 2.1.1.12) dependent on vitamin B₁₂-derived methylcobalamin. (8) In the liver, remethylation of HCYS by betaine-homocysteine methyltransferase (EC 2.1.1.5) in the presence of choline-derived betaine. (9) Synthesis of N^5,10-methylenetetrahydrofolate (5, 10-methyleneTHF) from THF coupled with the conversion of Ser into Gly through the action of pyridoxal-5′-phosphate-dependent serine hydroxymethyltransferase (EC 2.1.2.1). (10) Reduction of 5,10-methyleneTHF into 5-methylTHF catalyzed by N^5,10-methylenetetrahydrofolate reductase (MTHFR) (EC 1.5.1.20). EC, enzyme classification number of the International Union of Biochemistry.