6,7-dihydropteridine reductase

6,7-Dihydropteridine reductase (DHPR) is an enzyme that plays a crucial role in the metabolism of tetrahydrobiopterin (BH4), a cofactor essential for the hydroxylation of aromatic amino acids such as phenylalanine, tyrosine, and tryptophan. This enzyme is encoded by the QDPR gene in humans.

Function

DHPR is responsible for the reduction of quinonoid dihydrobiopterin (qBH2) back to BH4. This reaction is vital for maintaining adequate levels of BH4, which is necessary for the proper function of several hydroxylase enzymes. These enzymes are involved in the synthesis of important neurotransmitters, including dopamine, serotonin, and norepinephrine.

Clinical Significance

Deficiency in DHPR activity can lead to a rare metabolic disorder known as dihydropteridine reductase deficiency. This condition is characterized by hyperphenylalaninemia and can result in neurological symptoms due to impaired neurotransmitter synthesis. Early diagnosis and treatment are crucial to prevent severe developmental delays and neurological damage.

Structure

The structure of DHPR has been elucidated through X-ray crystallography, revealing a homodimeric enzyme with each subunit containing a NADH binding domain. The active site of DHPR is highly conserved and is responsible for the enzyme's catalytic activity.

Related Enzymes

DHPR is part of the pteridine reductase family, which includes other enzymes involved in the metabolism of pteridine derivatives. These enzymes share structural similarities and often have overlapping substrate specificities.

Related Pages

• Tetrahydrobiopterin
• Phenylalanine hydroxylase
• Dihydropteridine reductase deficiency
• Neurotransmitter synthesis