6,7-dihydropteridine reductase

Enzyme involved in the metabolism of tetrahydrobiopterin

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.

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 phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase. These enzymes are involved in the synthesis of important neurotransmitters such as dopamine, norepinephrine, and serotonin.

Structure

The enzyme is a homodimer, meaning it consists of two identical subunits. Each subunit binds one molecule of NADH or NADPH, which are used as electron donors in the reduction process. The structure of DHPR has been elucidated through X-ray crystallography, providing insights into its active site and substrate binding.

Genetics

The gene encoding DHPR is located on chromosome 4 in humans. Mutations in this gene can lead to a deficiency in DHPR activity, resulting in a rare metabolic disorder known as dihydropteridine reductase deficiency. This condition is characterized by elevated levels of phenylalanine in the blood, similar to phenylketonuria (PKU), and can lead to neurological problems if not treated.

Clinical significance

DHPR deficiency is a form of hyperphenylalaninemia, which can cause intellectual disability, seizures, and other neurological issues if untreated. Early diagnosis and treatment with a low-phenylalanine diet and BH4 supplementation can help manage the condition. Newborn screening programs often include tests for elevated phenylalanine levels to detect this and other related disorders.

Related pages

• Tetrahydrobiopterin
• Phenylalanine hydroxylase
• Phenylketonuria
• Neurotransmitter

Gallery

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  Structure of 6,7-dihydropteridine reductase