GTP Cyclohydrolase I Inhibition by the Prototypic Inhibitor 2,4-Diamino-6-Hydroxypyrimidine

The Protein Partners of GTP Cyclohydrolase I in Rat Organs

OBJECTIVE GTP cyclohydrolase I (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin biosynthesis and has been shown to be a promising therapeutic target in ischemic heart disease, hypertension, atherosclerosis and diabetes. The endogenous GCH1-interacting partners have not been identified. Here, we determined endogenous GCH1-interacting proteins in rat. METHODS AND RESULTS A pulldown an...

Defect in GTP-cyclohydrolase

Activation of peroxisome proliferator-activated receptor-{delta} enhances regenerative capacity of human endothelial progenitor cells by stimulating biosynthesis of tetrahydrobiopterin.

The mechanisms underlying the regenerative capacity of endothelial progenitor cells (EPCs) are not fully understood. We hypothesized that biosynthesis of tetrahydrobiopterin is an important mechanism responsible for the stimulatory effects of peroxisome proliferator-activated receptor-δ (PPARδ) activation on regenerative function of human EPCs. Treatment of human EPCs with a selective PPARδ ago...

HMG-CoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cells.

OBJECTIVE Endothelial nitric oxide synthase (eNOS) activity is supported by tetrahydrobiopterin (BH4), which appears to be important for generating protective NO but decreases uncoupling formation of superoxide. We investigated the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, in terms of BH4 metabolism in human umbilical vein endothelial cells (HUVECs). M...

Cloning and developmental expression of zebrafish GTP cyclohydrolase I

GTP cyclohydrolase I (GCH) catalyses the conversion of GTP to dihydroneopterin triphosphate, initiating the pteridine pathway. The final product tetrahydrobiopterin (H4biopterin) is the cofactor for neurotransmitter synthesis and for tyrosine supply during melanogenesis. Sepiapterin accumulates as a pigment. We cloned the zebrafish gch cDNA, which encodes a protein highly homologous to other ve...