METABOLISM OF HOMOCYSTEINE
Intracellular homocysteine can be remethylated to methionine-the transmethylation pathway, converted to cystathionine-the transsulfuration pathway, or exported from the cells. Pathway 1 is catalyzed by the enzyme methionine synthase, which requires cobalamin (vitamin B12) as a cofactor and folate {in the form methyltetrahydrofolate as cosubstrate. The remethylation pathway is favoured during relative methionine deficiency, and this recycling and conservation of homocysteine ensures adequate methionine maintenance. During pathway 2, the vitamin B6-dependent enzyme cystathionine -synthase catalyzes the irreversible condensation of homocysteine with serine to form cystathionine which is then broken down to cysteine and a-ketobutyrate. In the presence of excess methionine, the transsulfuration pathway is favoured by the upregulation of cystathionine f}synthase and downregulation of the remethylation pathway.
Release of homocysteine into the extracellular medium represents the third route of homocysteine removal from the cell. Such export is enhanced when production of homocysteine is increased, and reduced when production is inhibited. Thus, the amount of homocysteine in the extracellular media, such as plasma and urine, reflects the balance between intracellular production and utilization.
