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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 .
The recovery of methionine from homocysteine by transmethylation is depicted in reaction 4. The transmethylation cycle is depicted in reactions 1–4. Transmethylation is a biologically important organic chemical reaction in which a methyl group is transferred from one compound to another.
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.
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 ...
The methionine gene product MetR and the methionine intermediate homocysteine are known to positively regulate glyA. Homocysteine is a coactivator of glyA and must act in concert with MetR. [15] [16] On the other hand, PurR, a protein which plays a role in purine synthesis and S-adeno-sylmethionine are known to down regulate glyA.
Homocysteine is a non-protein amino acid, synthesized from methionine and either recycled back into methionine or converted into cysteine with the aid of the B-group vitamins [citation needed]. About 50% of homocysteine [citation needed] is converted back to methionine by remethylation via the methionine synthase major pathway.