Homocysteine metabolic pathways. In the methylation pathway, homocysteine acquires a methyl group either from betaine, a reaction that occurs mainly in the liver or from 5-methyltetrahydrofolate, a reaction which occurs in all tissues and is vitamin B12–dependent. In the transsulfuration pathway homocysteine condenses with serine to form cystathionine in a reaction that is catalyzed by CBS and requires PLP.