Nicotinic acid hydroxylase

While it has not yet been definitively determined that selenium is essential in the enzyme, this appears very likely. Nicotinic acid hydroxylase is the catalyst in the first step of a series of anaerobic reactions which result overall in the fermentation of nicotinic acid to acetate, ammonia, carbon dioxide and propionate The first reaction is shown below and is the addition of water to nicotinic acid to yield 6-oxonicotinic acid and to generate NADPH (Eq. 3). 

Recent studies demonstrated that C. barken produces increased levels of nicotinic acid hydroxylase when cultured in selenium rich media and that when the enzyme was purified from C. barken cells labeled with Se-selenite, the Se and the enzyme actmty co-purified . Further experiments are required to establish that selenium is indeed required by this enzyme and to identify the form of selenium present. 

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

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). 

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. 

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

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. 

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... 

Nicotinic acid hydroxylase Chlorate reductase Clostridium barkerii Proteus mirabilis 300000 2 Fe/S, FAD, Se... 

Nicotinic acid hydroxylase from Clostridium barkerii catalyzes reaction (55), the hydroxylation of a pyridine group, and has similarities to xanthine dehydrogenase. Nicotinic acid hydroxylase is a 300 000 molecular weight flavoprotein containing iron-sulfur and FAD centres, selenium1034 and a molybdopterin cofactor.1035 Formate dehydrogenase contains selenium as selenocysteine,1036 but this does not appear to be the case for nicotinic acid hydroxylase. The possibility that the selenium is incorporated into the molybdopterin cannot be excluded at present. 

Ao-Nicotinic acid hydroxylase Bacterial CC2P2Y2 (MPTpC)Mo(0)(S)bc Unknown 2 Fe2S2, 2 FAD 246... 

Nicotinic acid hydroxylase Bacterial a2, aPy CC2P2Y2 LMo(0)(S)bc Unknown Fe2S2, FAD, (Se) 247-250... 

Qumoline-2-oxidoreductase Isoqumolme 1-oxidoreductase Qumoline-4-carboxylate-2-oxidoreductase Qumaldine-4-oxidoreductase Qumaldic add 4-oxidoreductase Nicotinic acid hydroxylase (dehydrogenase)... 

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