Defects in Auxiliary Redox Proteins Lead to Functional Methionine Synthase Deficiency

Methionine synthase and neural tube defects.

It has been indicated lately that higher plasma homocysteine is one of the risk factors in neural tube defects(NTDs) and vascular disease. Methionine synthase is a key enzyme in homocysteine metabolism. The defects of methionine synthase activity could result in hyperhomocysteinemia and methionine auxotrophy. The gene mutations of methionine synthase with the epidemiological studies of NTDs are...

cblE type of homocystinuria due to methionine synthase reductase deficiency: functional correction by minigene expression.

The cblE type of homocystinuria is a rare autosomal recessive disorder caused by impaired reductive activation of methionine synthase. Although earlier biochemical studies proposed that the methionine synthase enzyme might be activated by two different reducing systems, mutations were reported in only the methionine synthase reductase gene (MTRR) in cblE patients. The pathogenicity of MTRR muta...

Defects in human methionine synthase in cblG patients.

Inborn errors resulting in isolated functional methionine synthase deficiency fall into two complementation groups, cblG and cblE. Using biochemical approaches we demonstrate that one cblG patient has greatly reduced levels of methionine synthase while in another, the enzyme is specifically impaired in the reductive activation cycle. The biochemical data suggested that low levels of methionine ...

Homocystinuria due to cystathionine synthase deficiency: the metabolism of L-methionine.

Cobalamin-dependent methionine synthase.

Cobalamin-dependent methionine synthase catalyzes the transfer of a methyl group from N5-methyltetrahydrofolate to homocysteine, producing tetrahydrofolate and methionine. Insufficient availability of cobalamin, or inhibition of methionine synthase by exposure to nitrous oxide, leads to diminished activity of this enzyme. In humans, severe inhibition of methionine synthase results in the develo...