QDPR

The QDPR gene provides instructions for making an enzyme called quinoid dihydropteridine reductase. This enzyme is responsible for one step in the chemical pathway that recycles a molecule called tetrahydrobiopterin (BH4).

Tetrahydrobiopterin plays a critical role in processing several protein building blocks (amino acids) in the body. For example, it works with the enzyme phenylalanine hydroxylase to convert an amino acid called phenylalanine into another amino acid, tyrosine. Tetrahydrobiopterin is also involved in reactions that produce chemicals in the brain called neurotransmitters, which transmit signals between nerve cells. Because it helps enzymes carry out chemical reactions, tetrahydrobiopterin is known as a cofactor.

When tetrahydrobiopterin interacts with enzymes during chemical reactions, the cofactor is altered and must be recycled to a usable form. Quinoid dihydropteridine reductase is one of two enzymes that recycle tetrahydrobiopterin in the body.

tetrahydrobiopterin deficiency - caused by mutations in the QDPR gene

When QDPR mutations underlie tetrahydrobiopterin deficiency, the condition is known as dihydropteridine reductase (DHPR) deficiency. More than 30 disease-causing mutations in this gene have been identified. Most of these mutations change single amino acids in quinoid dihydropteridine reductase, although some mutations insert small amounts of DNA into the QDPR gene or disrupt the way the gene's instructions are used to make the enzyme.

Mutations in the QDPR gene greatly reduce or eliminate the activity of quinoid dihydropteridine reductase. Without enough of this enzyme, tetrahydrobiopterin is not recycled properly. As a result, this cofactor is not available to participate in chemical reactions such as the conversion of phenylalanine to tyrosine. If phenylalanine from the diet is not converted to tyrosine, it can build up to toxic levels in the blood and other tissues. Nerve cells in the brain are particularly sensitive to phenylalanine levels, which is why excessive amounts of this substance can cause brain damage.

Additionally, a reduction in quinoid dihydropteridine reductase activity disrupts the production of certain neurotransmitters in the brain. Because neurotransmitters are necessary for normal brain function, changes in the levels of these brain chemicals contribute to mental impairment in people with tetrahydrobiopterin deficiency.