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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 .
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.
A blood test can be performed to quantify total homocysteine concentration in the plasma, of which approximately 80% is generally protein-bound. Classification of hyperhomocysteinemia is defined with respect to serum concentration as follows: [citation needed] Moderate: 15–30 nmol/mL (or μmol/L) Intermediate: 30–100 nmol/mL; Severe: > 100 ...
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 ...
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.
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.