PCBD1

The PCBD1 gene provides instructions for making an enzyme called pterin-4 alpha-carbinolamine dehydratase. 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. Pterin-4 alpha-carbinolamine dehydratase is one of two enzymes that recycle tetrahydrobiopterin in the body.

tetrahydrobiopterin deficiency - caused by mutations in the PCBD1 gene

When PCBD1 mutations underlie tetrahydrobiopterin deficiency, the condition is known as pterin-4 alpha-carbinolamine dehydratase (PCD) deficiency. At least nine disease-causing mutations in this gene have been identified. Some of these mutations change single amino acids in pterin-4 alpha-carbinolamine dehydratase, while other mutations introduce a premature stop signal in the instructions for making this enzyme.

PCBD1 mutations reduce the activity of pterin-4 alpha-carbinolamine dehydratase. A reduction in this enzyme's activity affects the body's ability to recycle tetrahydrobiopterin. As a result, less of this cofactor is available to participate in chemical reactions such as the conversion of phenylalanine to tyrosine. If phenylalanine from the diet is not converted to tyrosine, the excess can build up in the bloodstream and other tissues. People with PCBD1 mutations usually have elevated levels of phenylalanine in the blood, although this form of tetrahydrobiopterin deficiency rarely causes significant medical problems. Researchers believe that other enzymes may compensate for the reduced activity of pterin-4 alpha-carbinolamine dehydratase.