Tetrahydrobiopterin deficiency and brain nitric oxide synthase in the hph1 mouse

摘要: Tetrahydrobiopterin (BH4) is the cofactor for aromatic amino acid monoxygenase group of enzymes and all known isoforms nitric oxide synthase (NOS). Inborn errors BH4 metabolism lead to hyperphenylalaninaemia impaired catecholamine serotonin turnover. The effects deficiency on brain (NO) are not known. In this study we have used thehph-1 mouse, which displays GTP cyclohydrolase deficiency, NOS. presence exogenous BH4, NOS specific activity was virtually identical in control andhph-1 preparations. However, omission from reaction buffer led a significant 20% loss preparations only. TheKm arginine when present buffer. absence cofactor, theKm 3-fold greater 5-fold forhph-1 It concluded that (a) does regulate intracellular concentration NOS; (b) less binding occurs states; (c) has potent effect affinity arginine; (d) availability may become severely limiting states. Since, suboptimal concentrations or arginine, additionally form oxygen free-radicals, it postulated severe states NO formation central nervous system subjected increased oxidative stress.