Nicotinate hydroxylase

Stadtman 1971 Kung et al. 1971). Degradation is initiated by hydroxylation of the ring, and the level of nicotinic acid hydroxylase is snbstantially increased by the addition of selenite to the medinm (Imhoff and Andreesen 1979). Nicotinate hydroxylase from Clostridium barkeri contains molybdenum that is coordinated to seleninm, which is essential for hydroxylase activity (Gladyshev et al. 1994). The most remarkable featnre of the pathway is the mechanism whereby 2-methylene-glntarate is converted into methylitaconate by a coenzyme Bi2-mediated reaction (Knng and Stadtman 1971). 

This enzyme [EC 1.5.1.13], also known as nicotinate hydroxylase, catalyzes the reaction of nicotinate with NADP+ and water to produce 6-hydroxynicotinate and NADPH. This iron-dependent flavoprotein will also oxidize NADPH. 

Dilworth GL (1982) Properties of the selenium-containing moiety of nicotinic acid hydroxylase from Clostridium barkeri. Arch Biochem Biophys 219 30-38. 

Freudenberg W, K Konig, JR Andressen (1988) Nicotine dehydrogenase from Arthrobacter oxidans a molybdenum-containing hydroxylase. FEMS Microbiol Lett 52 13-18. 

Gladyshev VN, SV Khangulov, TC Stadtman (1994) Nicotinic acid hydroxylase from Clostridium barkeri electron paramagnetic resonance studies show that selenium is coordinated with molybdenum in the catalytically active selenium-dependent enzyme. Proc Natl Acad Sci USA 91 232-236. 

Hirschberg R, JC Ensign (1971b) Oxidation of nicotinic acid by a Bacillus species purification and properties of nicotinic acid and 6-hydroxynicotinic acid hydroxylases. J Bacterial 108 751-756. 

Imhoff D, JR Andreesen (1979) Nicotinic acid hydroxylase from Clostridium barkeri selenium-dependent formation of active enzyme. FEMS Microbiol Lett 5 155-158. 

Anney, R.J.L., Olsson, C.A., Lotfi-Miri, M., Patton, G.C., Williamson, R. Nicotine dependence in a prospective population-based study of adolescents the protective role of a functional tyrosine hydroxylase polymorphism. Pharmacogenetics. 14 73, 2004. 

In the first family, the metal is coordinated by one molecule of the pterin cofactor, while in the second, it is coordinated to two pterin molecules (both in the guanine dinucleotide form, with the two dinucleotides extending from the active site in opposite directions). Some enzymes also contain FejSj clusters (one or more), which do not seem to be directly linked to the Mo centers. The molybdenum hydroxylases invariably possess redox-active sites in addition to the molybdenum center and are found with two basic types of polypeptide architecture. The enzymes metabolizing quinoline-related compounds, and derivatives of nicotinic acid form a separate groups, in which each of the redox active centers are found in separate subunits. Those enzymes possessing flavin subunits are organized as a2jS2A2, with a pair of 2Fe-2S centers in the (3 subunit, the flavin in the (3 subunit, and the molybdenum in the y subunit. 

Since nicotine has wide ranging effects on the central nervous system it seems likely that pharmacogenomic effects on the development of nicotine dependence will span several neurotransmitter systems. One study found an association between a polymorphism in dopamine /1-hydroxylase and level of tobacco consumption [20]. This enzyme is important in noradrenaline synthesis and it is tempting to speculate that genetically regulated variations in activity might influence susceptibility to nicotine withdrawal symptoms mediated by noradrenergic pathways, but more information is required on the molecular effects of the polymorphism. 

Another selenium-containing molybdenum hydroxylase that has been isolated from Clostridium barkeri (identical to Eubacterium barkeri) is nicotinic acid hydroxylase (NAH). Clostridium barkeri was isolated initially as a fermentor of nicotinic acid and thus NAH is a key enzyme in the efficient fermentation of nicotinic acid as a source of carbon and energy. NAH contained selenium when purified from cells labeled with Se-selenite. However, this label was lost during denaturing gel electrophoresis and also on heating of the enzyme (Dilworth 1982). Exhaustive analysis of selenium-labeled alkylation products of NAH under various conditions revealed selenium was bound as a labile cofactor (Dilworth 1982), and not as seleno-cysteine. This report was the first to describe a selenium-dependent enzyme that did not contain selenium in the form of selenocysteine. 

Raunio H, Syngelma T, Pasanen M, Juvonen R, Honkakoski P, Kairaluoma MA, Sotaniemi E, Lang MA, Pelkonen O (1988) Immunochemical and catalytical studies on hepatic coumarin 7-hydroxylase in man, rat, and mouse, Biochem Pharmacol 37 3889-3895 Raunio H, Pokela N, Puhakainen K, Rahnasto M, Mauriala T, Auriola S, Juvonen RO (2008) Nicotine metabolism and urinary ehmination in mouse in vitro and in vivo, Xenobiotica 38 34 7... 

R)-2-METHYLMALATE DEHYDRATASE NICOTINATE DEHYDROGENASE NITRATE REDUCTASE NITRITE REDUCTASE PHENYLALANINE MONOOXYGENASE PROLYL 3-HYDROXYLASE PROLYL 4-HYDROXYLASE PROTOCATECHUATE 3,4-DIOXYGENASE PROTOCATECHUATE 4,5-DIOXYGENASE RIESKE IRON-SULFUR PROTEIN RUBREDOXIN... 

CYP2A6 is responsible for the majority of coumarin 7-hydroxylase and nicotine C-oxidase activity in hepatic tissue. Substrate selectivity of 2A6 and 2A5 (mouse enzyme) was studied using 23 lactone-containing compounds... 

Preclinical studies have shown that prenatal exposure to nicotine reduces brain weight, decreases cortical thickness, and produces abnormalities of pyramidal neuron maturation (Lee, 1998). Reduction in CNS markers of catecholamine activity, such as tyrosine hydroxylase activity, have been observed however, these appear to normalize by adolescence (Levitt, 1998). 

A purine hydroxylase from fungi,639 bacterial quinoline and isoquinoline oxidoreductases,640/641 and a selenium-containing nicotinic acid hydroxylase from Clostridium barberei6i2 are members of the... 

Nicotinic acid adenine dinucleotide phosphate (NAA 315 Nicotinic acid hydroxylase 825 Nidogen 437 Ninhydrin 120,121s Nitrate reductase(s)... 

Carbon monoxide oxidase, nicotinic acid hydroxylase, formate dehydrogenase and other 662... 

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