Thetin—homocysteine S-methyltransferase

Thetin—homocysteine S-methyltransferase is an enzyme that plays a crucial role in the metabolism of amino acids, specifically in the biochemical pathway that metabolizes homocysteine into methionine. This enzyme is also known by its systematic name, 5-methyltetrahydrofolate-homocysteine methyltransferase, and is commonly abbreviated as MTR, from its gene name. The enzyme's activity is essential for maintaining low levels of homocysteine and for the synthesis of methionine, an essential amino acid required for the synthesis of proteins and other critical molecules like S-adenosylmethionine, a major methyl donor in numerous methylation reactions.

Function

Thetin—homocysteine S-methyltransferase catalyzes the final step in the methionine synthesis pathway. It transfers a methyl group from 5-methyltetrahydrofolate (5-MTHF) to homocysteine, producing methionine and tetrahydrofolate (THF). This reaction is not only crucial for the synthesis of methionine but also for the regeneration of THF, which is a necessary cofactor in the synthesis of purines and thymidylate, thus playing a vital role in DNA synthesis and repair.

Clinical Significance

Alterations in the activity of Thetin—homocysteine S-methyltransferase can lead to elevated levels of homocysteine, a condition known as hyperhomocysteinemia. This condition has been associated with an increased risk of cardiovascular diseases, such as atherosclerosis and thrombosis, as well as neurological disorders, including Alzheimer's disease and other forms of dementia. Genetic mutations in the MTR gene, which encodes this enzyme, can result in reduced enzyme activity and are a known risk factor for these conditions.

Genetics

The MTR gene is located on chromosome 1 (1q43), spanning over 105 kb and comprising 34 exons. Mutations in this gene can lead to a rare inherited disorder known as Methionine synthase deficiency, which is characterized by megaloblastic anemia, developmental delay, and homocystinuria.

Treatment and Management

Management of conditions associated with Thetin—homocysteine S-methyltransferase dysfunction often involves dietary supplementation with vitamin B12 and folic acid, as these are cofactors required for the enzyme's activity. In cases of genetic mutations leading to enzyme deficiency, more specific treatments may be required, including methionine supplementation and management of symptoms associated with the condition.

See Also

• Methionine
• Homocysteine
• Methionine synthase deficiency
• Hyperhomocysteinemia
• Vitamin B12
• Folic acid