5-methyltetrahydrofolate-homocysteine methyltransferase reductase
The MTRR gene provides instructions for making an enzyme called methionine synthase reductase. This enzyme is required for the proper function of another enzyme called methionine synthase. Methionine synthase helps process amino acids, which are the building blocks of proteins. Specifically, it converts the amino acid homocysteine to another amino acid called methionine. After a period of being turned on (active), methionine synthase turns off (becomes inactive). Methionine synthase reductase reactivates methionine synthase so the enzyme can continue to produce methionine.
At least 20 mutations in the MTRR gene have been identified in people with homocystinuria. Some of these mutations change single amino acids in methionine synthase reductase. Other mutations lead to an abnormally small, nonfunctional version of the enzyme. All these mutations prevent the enzyme from functioning normally. Without methionine synthase reductase, methionine synthase cannot convert homocysteine to methionine. As a result, homocysteine builds up in the bloodstream, and the amount of methionine is reduced. Some of the excess homocysteine is excreted in urine. Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.
A specific version (variant) of the MTRR gene may be associated with an increased risk of various health problems before birth. The variant replaces a building block of DNA (nucleotide) called adenine with the nucleotide guanine at position 66 of the MTRR gene (written as A66G). This variant is associated with birth defects that occur during the development of the brain and spinal cord (neural tube defects). This variant may also increase the risk of having a child with Down syndrome, a condition characterized by intellectual disability and associated health problems. Researchers have not determined why there may be a connection between the A66G variant of the MTRR gene and the risk of neural tube defects or Down syndrome. Many factors play a part in determining the risk of these disorders.
- methionine synthase reductase