Gene/Protein Disease Symptom Drug Enzyme Compound
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(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for aromatic amino acid hydroxylases, such as phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), tryptophan hydroxylase, and nitric oxide synthase, which catalyze physiologically important reactions in mammals. The biosynthesis and metabolism of BH4 is usually studied mostly in the liver and only slightly in the brain, as the BH4 level in the liver is relatively high because BH4 is required for the reaction of PAH. We found that GTP (guanosine triphosphate) cyclohydrolase I, an enzyme for the biosynthesis of BH4, is a causative gene for DOPA (3,4-dihydroxyphenylalanine)-responsive dystonia (also called Segawa's disease), and that partial deficiency of BH4 leads to the dysfunction of the nigrostriatal dopaminergic neurons without hyperphenylalaninemia. We analyzed BH4-deficient mice that were produced by disruption of a BH4-synthesizing gene by a gene-knockout technique. We found that the protein amount of TH was highly dependent on the amount of BH4, especially in nerve terminals. Our research suggests that BH4 metabolism in the brain should be different from that in the liver, and that altered metabolism of BH4 should lead to neuropsychiatric disorders including Parkinson's disease.
Chem Rec 2008
PMID:Metabolism of tetrahydrobiopterin: its relevance in monoaminergic neurons and neurological disorders. 1910 67

Proton dissociation of an aqua-Ru-quinone complex, [Ru(trpy)(q)(OH2)]2+ (trpy = 2,2' : 6',2''-terpyridine, q = 3,5-di-t-butylquinone) proceeded in two steps (pK(a) = 5.5 and ca. 10.5). The first step simply produced [Ru(trpy)(q)(OH)]+, while the second one gave an unusual oxyl radical complex, [Ru(trpy)(sq)(O-*)]0 (sq = 3,5-di-t-butylsemiquinone), owing to an intramolecular electron transfer from the resultant O2- to q. A dinuclear Ru complex bridged by an anthracene framework, [Ru2(btpyan)(q)2(OH)2]2+ (btpyan = 1,8-bis(2,2'-terpyridyl)anthracene), was prepared to place two Ru(trpy)(q)(OH) groups at a close distance. Deprotonation of the two hydroxy protons of [Ru2(btpyan)(q)2(OH)2]2+ generated two oxyl radical Ru-O-* groups, which worked as a precursor for O2 evolution in the oxidation of water. The [Ru2(btpyan)(q)2(OH)2](SbF6)2 modified ITO electrode effectively catalyzed four-electron oxidation of water to evolve O2 (TON = 33500) under electrolysis at +1.70 V in H2O (pH 4.0). Various physical measurements and DFT calculations indicated that a radical coupling between two Ru(sq)(O-*) groups forms a (cat)Ru-O-O-Ru(sq) (cat = 3,5-di-t-butylcathechol) framework with a mu-superoxo bond. Successive removal of four electrons from the cat, sq, and superoxo groups of [Ru2(btpyan)(cat)(sq)(mu-O2-)]0 assisted with an attack of two water (or OH-) to Ru centers, which causes smooth O2 evolution with regeneration of [Ru2(btpyan)(q)2(OH)2]2+. Deprotonation of an Ru-quinone-ammonia complex also gave the corresponding Ru-semiquinone-aminyl radical. The oxidized form of the latter showed a high catalytic activity towards the oxidation of methanol in the presence of base. Three complexes, [Ru(bpy)2(CO)2]2+, [Ru(bpy)2(CO)(C(O)OH)]+, and [Ru(bpy)2(CO)(CO2)]0 exist as an equilibrium mixture in water. Treatment of [Ru(bpy)2(CO)2]2+ with BH4- gave [Ru(bpy)2(CO)(C(O)H)]+, [Ru(bpy)2(CO)(CH2OH)]+, and [Ru(bpy)2(CO)(OH2)]2+ with generation of CH3OH in aqueous conditions. Based on these results, a reasonable catalytic pathway from CO2 to CH3OH in electro- and photochemical CO2 reduction is proposed. A new pbn (pbn = 2-pyridylbenzo[b]-1,5-naphthyridine) ligand was designed as a renewable hydride donor for the six-electron reduction of CO2. A series of [Ru(bpy)(3-n)(pbn)n]2+ (n = 1, 2, 3) complexes undergoes photochemical two- (n = 1), four- (n = 2), and six-electron reductions (n = 3) under irradiation of visible light in the presence of N(CH2CH2OH)3.
Chem Rec 2009
PMID:Metal-catalyzed reversible conversion between chemical and electrical energy designed towards a sustainable society. 1950 3