molybdenum cofactor synthesis 2

The MOCS2 gene provides instructions for making two different proteins, MOCS2A and MOCS2B, which combine to form an enzyme called molybdopterin synthase. Molybdopterin synthase performs the second of a series of reactions in the formation (biosynthesis) of a molecule called molybdenum cofactor. Molybdenum cofactor, which contains the element molybdenum, is essential to the function of several enzymes called sulfite oxidase, aldehyde oxidase, xanthine dehydrogenase, and mitochondrial amidoxime reducing component (mARC). These enzymes help break down (metabolize) different substances in the body, some of which are toxic if not metabolized.

MOCS2 gene mutations cause a disorder called molybdenum cofactor deficiency. This disorder is characterized by seizures that begin early in life and brain dysfunction that worsens over time (encephalopathy); the condition is usually fatal by early childhood. At least a dozen mutations in the MOCS2 gene have been found to cause a form of the disorder designated type B or complementation group B.

The MOCS2 gene mutations involved in molybdenum cofactor deficiency likely eliminate the function of MOCS2A, MOCS2B, or both, although in rare cases that are less severe, some protein function may remain. Without either piece of molybdopterin synthase, molybdenum cofactor biosynthesis is impaired. Loss of the cofactor impedes the function of the metabolic enzymes that rely on it.

The resulting loss of enzyme activity leads to buildup of certain chemicals, including sulfite, S-sulfocysteine, xanthine, and hypoxanthine, and low levels of another chemical called uric acid. (Testing for these chemicals can help in the diagnosis of this condition.) Sulfite, which is normally broken down by sulfite oxidase, is toxic, especially to the brain. Researchers suggest that damage caused by the abnormally high levels of sulfite (and possibly other chemicals) leads to encephalopathy, seizures, and the other features of molybdenum cofactor deficiency.

Cytogenetic Location: 5q11, which is the long (q) arm of chromosome 5 at position 11

Molecular Location: base pairs 53,095,679 to 53,109,772 on chromosome 5 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 5q11, which is the long (q) arm of chromosome 5 at position 11
  • MOCO1
  • molybdenum cofactor biosynthesis protein E
  • molybdopterin synthase catalytic subunit large subunit MOCS2B
  • molybdopterin synthase small and large subunit
  • molybdopterin synthase sulfur carrier subunit
  • molybdopterin synthase sulfur carrier subunit small subunit MOCS2A
  • MPTS