The list also includes phenylketonuria (PKU), Tetrahydrobiopterin
Deficiency, and hemophilia--diseases that BioMarin either has an approved therapy for or is developing one.
Keywords: Phenylalanine, Hyperphenylalaninemia, Classification, Phenylalanine hydroxylase deficiency, Tetrahydrobiopterin
It also reduces eNOS activity by interacting with tetrahydrobiopterin
, a cofactor of eNOS.
These enzymes need a number of essential cofactors such as calmodulin (CaM), tetrahydrobiopterin
(H4B), flavin mononucleotide, FAD and NADPH in order to function (3).
ROS can be produced in the cell by various enzymes including NADPH oxidase (NOX) and nitric oxide synthase (NOS) owing to a lack of tetrahydrobiopterin
cofactor (BH4) (Finkel, 1999; Sorescu & Griendling, 2002; Droge, 2002).
Laminar shear stress induced by blood flow activates endothelial nitric oxide synthase (eNOS) in the presence of cofactors, such as tetrahydrobiopterin
(BH4) which acts upon L-arginine, to produce nitric oxide (NO).17 eNOS is also activated by bradykinin, adenosine, vascular endothelial growth factor (VEGF) and serotonin.18
Katusic, "Activation of peroxisome proliferator-activated receptor-5 enhances regenerative capacity of human endothelial progenitor cells by stimulating biosynthesis of tetrahydrobiopterin
," Hypertension, vol.
Increased NOS activity has been reported to be accompanied by GTPCH 1 activation and tetrahydrobiopterin
(BH4) formation .
Nitric oxide synthesis dysregulation and tetrahydrobiopterin
depletion were probably related to impaired conversion of phenylalanine to tyrosine and the accumulation of phenylalanine [14, 15].
GCH1 is an enzyme that mediates the rate-limiting step in the biosynthesis of tetrahydrobiopterin
(B[H.sub.4]), an essential cofactor in the production of dopamine.
Antonopoulos et al., "Induction of vascular GTP-cyclohydrolase I and endogenous tetrahydrobiopterin
synthesis protect against inflammation-induced endothelial dysfunction in human atherosclerosis," Circulation, vol.
This decrease may be linked to reduced phenylalanine 4-hydroxylase (PAH) activity due to a loss of neopterin, a precursor of PAH's cofactor tetrahydrobiopterin