Phenylalanine 4-monooxygenase

Phenylalanine 4-monooxygenase is an enzyme that in humans is encoded by the PAH gene. This enzyme is crucial in the metabolism of the amino acid phenylalanine, converting it into tyrosine, another amino acid. This reaction is a key step in the phenylalanine catabolic pathway, which is important for the degradation and utilization of dietary phenylalanine.

Function

Phenylalanine 4-monooxygenase catalyzes the hydroxylation of phenylalanine to tyrosine, a reaction that requires molecular oxygen (O2) and tetrahydrobiopterin (BH4) as cofactors. This enzyme plays a vital role in amino acid degradation, particularly in the liver, and is essential for protein synthesis and the production of neurotransmitters and hormones, including dopamine, norepinephrine, and thyroid hormones.

Genetics

The PAH gene, located on chromosome 12 in humans, encodes the phenylalanine 4-monooxygenase enzyme. Mutations in this gene can lead to a deficiency in the enzyme, resulting in a metabolic disorder known as Phenylketonuria (PKU). PKU is characterized by an inability to metabolize phenylalanine, leading to its accumulation in the body and potentially causing intellectual disability and other neurological problems if not treated.

Clinical Significance

Phenylalanine 4-monooxygenase deficiency, or PKU, is a significant concern in newborns. Newborn screening programs worldwide include a test for PKU, allowing for early diagnosis and treatment. Management of PKU involves a diet low in phenylalanine, which helps prevent the adverse effects associated with the accumulation of phenylalanine in the body.

Biochemical Pathway

The conversion of phenylalanine to tyrosine by phenylalanine 4-monooxygenase is a critical step in the phenylalanine degradation pathway. Tyrosine itself is a precursor for several important biochemical pathways, including the synthesis of melanin, catecholamines, and thyroid hormones. The activity of phenylalanine 4-monooxygenase, therefore, has broad implications for human health, affecting everything from pigmentation to stress response and metabolic regulation.

See Also

• Amino acid metabolism
• Inborn error of metabolism
• Tyrosine hydroxylase