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Homocysteine (left) and methionine (right) are related by demethylation and remethylation. Remethylation is a major step in the conversion of homocysteine to the essential amino acid methionine . The remethylation process involves the enzyme methionine synthase (MS), which requires vitamin B 12 as a cofactor, and also depends indirectly on ...
The production of homocysteine through transsulfuration allows the conversion of this intermediate to methionine, through a methylation reaction carried out by methionine synthase. The reverse pathway is present in several organisms, including humans, and involves the transfer of the thiol group from homocysteine to cysteine via a similar ...
In the body, homocysteine can be recycled into methionine or converted into cysteine with the aid of vitamin B 6, B 9, and B 12. [ 3 ] High levels of homocysteine in the blood ( hyperhomocysteinemia ) is regarded as a marker of cardiovascular disease, likely working through atherogenesis , which can result in ischemic injury .
Methylenetetrahydrofolate reductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the MTHFR gene. [5] Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine.
MTHFR is the rate-limiting enzyme in the methyl cycle, which includes the conversion of homocysteine into methionine. Defects in variants of MTHFR can therefore lead to hyperhomocysteinemia. [9] There are two common variants of MTHFR deficiency. In the more significant of the two, the individual is homozygous for the 677T polymorphism.
Elevated homocysteine is an independent risk factor for cardiovascular disease and inversely correlated to consumed vitamin B12/B6 and folate levels. [37] Homocysteine methylation to methionine is catalyzed by MTR, resulting in appropriate intracellular levels of methionine and tetrahydrofolate, alongside non-toxic homocysteine levels.
Methionine synthase catalyzes the final step in the regeneration of methionine (Met) from homocysteine (Hcy). Both the cobalamin-dependent and cobalamin-independent forms of the enzyme carry out the same overall chemical reaction, the transfer of a methyl group from 5-methyltetrahydrofolate (N 5 -MeTHF) to homocysteine, yielding ...
Cystathionine beta-lyase catalyzes the production of homocysteine, a direct precursor to methionine. Methionine is an essential amino acid for bacteria that is required for protein synthesis and the synthesis of S-adenosylmethionine ; thus, the amino acid is directly linked to DNA replication .