Tetrahydrobiopterin in energy metabolism and metabolic diseases

Tetrahydrobiopterin (BH4) is an endogenous cofactor for various enzymatic conversions of essential biomole-cules including nitric oxide, tyrosine, dopamine, serotonin and phenylalanine. Depending on the physiological functions of these molecules, BH4 plays multiple roles in the cardiovascular, immune, nervous and endocrine systems. A deficiency of BH4 or an imbalance of the redox state of biopterin has been implicated in various cardiovascular and metabolic diseases. Therefore, supplementation with BH4 is considered as a therapeutic option for these diseases. In addition to the classical nitric oxide synthase (NOS)-dependent role of BH4, recent studies proposed novel NOS-independent roles of BH4 in health and disease conditions. This article reviews the updated role of BH4 in mitochondrial regulation, energy metabolism and cardiovascular and metabolic diseases.