2005 Volume 79 Issue 2 Pages 87-95
Tetrahydrobipterin (BH4) is an essential cofactor for three aromatic amino acid monooxygenases phenylalanine, tyrosine, and tryptophane hydroxylases (PAH, TH, and TPH)-and for nitric oxide synthase (NOS). BH4 plays crucial roles in phenylalanine metabolism, neurotransmitter synthesis, vasodilation, and immune response. In mammals, BH4 synthesis is regulated by various hormones and cytokines, and other stimuli. BH4 deficiency is responsible for malignant type of hyperphenylalaninemla and dopa-responsive dystonia, and is recently supposed to be involved in endothelial dysfunction and neurodegeneration. Recent works have shown that administration of BH4 is effective for patients with hyperphenylalanlnemia who have a genetic defect in the PAH gene, although their BH4 levels are normal. More notables are the beneficial effects of BH4 supplementation on endothelial dysfunction caused by hypercholesterolemia, diabetes, hypertension, and chronic smoking. In this review, we summarize recent progress in the BH4 research.
