PRODH

The PRODH gene provides instructions for producing the enzyme proline oxidase, which is found primarily in the brain, liver, and kidney. Within cells of these organs, this enzyme functions in energy-producing structures called mitochondria.

Proline oxidase begins the process of breaking down the protein building block (amino acid) proline by starting the reaction that converts it to pyrroline-5-carboxylate. A subsequent step converts this intermediate product to the amino acid glutamate. The conversion between proline and glutamate is important in maintaining a supply of the amino acids needed for protein production, and for energy transfer within the cell.

hyperprolinemia - caused by mutations in the PRODH gene

At least 15 mutations in the PRODH gene have been found to reduce the activity of the proline oxidase enzyme. These mutations substitute one amino acid for another amino acid in the enzyme, causing it to perform its function in proline breakdown (degradation) less efficiently. A reduction in proline oxidase function results in a buildup of proline in the body, and in severe cases of hyperprolinemia can cause seizures, intellectual disability, or other neurological or psychiatric problems.

other disorders - associated with the PRODH gene

Several studies have shown an association between variations in the PRODH gene and psychiatric disorders such as schizophrenia, while others have shown no significant association. Most of the variations in the PRODH gene result in the substitution of one amino acid for another in the proline dehydrogenase enzyme. The amino acid substitution reduces the enzyme's activity, resulting in less efficient breakdown of proline. Researchers believe that elevated proline levels may affect the action of certain chemicals that transmit signals between neurons in the brain (neurotransmitters), resulting in an increased risk of psychiatric disorders.