Nicotinamide adenine oxidoreductase

Axcell BC, PJ Geary (1973) The metabolism of benzene by bacteria. Purification and some properties of the ezyme cw-l,2-dihydroxycyclohexa-3,5-diene (nicotinamide adenine dinucleotide) oxidoreductase (ciT-benzene glycol dehydrogenase). Biochem J 136 927-934. 

NAD(P)+ as Anode Mediator. A majority of redox enzymes require the cation nicotinamide adenine dinucleotide, possibly phosphorylated (NAD(P)+) as a cofactor. Of the oxidoreductases listed in Enzyme Nomenclature, over 60% have NAD(P)+ as a reactant or product.For example, methanol can be oxidized to form formaldehyde by methanol dehydrogenase (MDH, EC 1.1.1.244) according to... 

Mikalsen A, Capellmann M, Alexander J. 1995. The role of iron chelators and oxygen in the reduced nicotinamide adenine dinucleotide phosphate-cytochrome P450 oxidoreductase-dependent chromium(VI) reduction. Analyst 120 935-938. 

Figure 17.4 The electron transport chain of mitochondria. Triangles indicate sites of inhibition by various compounds. Cyt, cytochrome ETF, electron transfer flavoprotein. (Reproduced with permission from Moreadith RW, Batshaw ML, Ohnishi T, Kerr D, Knox B, Jackson D, Hruben R, Olson J, Reynafarje B, Lehninger AL. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis J Clin Invest 74 685-697, 1984.)...

NAADP, nicotinic acid adenine dinucleotide 2 -phosphate NAADP-R, nicotinic acid adenine dinucleotide 2 -phosphate receptor nACh-R, nicotinic acetylcholine receptor NADH DH, NADH dehydrogenase NADH/NAD"1", reduced/oxidized nicotinamide adenine dinucleotide NADH-U() OR, NADH-ubiquinone oxidoreductase... 

Enzyme biosensors are usually constructed with enzymes that are oxido-reductases. The largest known group of oxidoreductases is dehydrogenases, of which more than 250 depend on the soluble coenzyme nicotinamide adenine dinucleotide, NAD "/NADH couple. Excellent review for electrocatalytic... 

Both groups of reactions are found in bacteria (14), all higher animals (i5), and plants (16) however, oxidative phosphorylation is responsible for 90 % of the oxygen consumed (i 7). Oxidative phosphorylation is driven by the respiratory electron-transport system that is embedded in the lipoprotein inner membrane of eukaryotic mitochondria and in the cell membrane of prokaryotes. It consists of four complexes (Scheme I). The first is composed of nicotinamide adenine dinucleotide (NADH) oxidase, flavin mononucleotide (FMN), and nonheme iron-sulfur proteins 18,19), and it transfers electrons from NADH to ubiquinone. The second is composed of succinate dehydrogenase (SDH), flavin adenine dinucleotide (FAD), and nonheme iron-sulfur proteins (20), and it transfers electrons from succinate to ubiquinone 21, 22). The third is composed of cytochromes b and c, and nonheme iron-sulfur proteins (23), and it transfers electrons from ubiquinone (UQ) to cytochrome c 24). The fourth complex consists of cytochrome c oxidase [ferrocytochrome c 0 oxidoreductase EC 1.9.3.1 25)] which transfers electrons from cytochrome c to O2 26, 27). 

T14484C represent 95% of those identified. Mutation G11778A was the first described, is the most common, and accounts for at least 50% of cases. In most affected individuals, LHON mutations appear to be homoplasmic, with only mutant mtDNA detected, but in 15% of cases, the mutations are heteroplasmic, with a mixture of both normal and mutant mtDNA detected. Each of the common mutations affects a subrmit of the nicotinamide adenine dinucleotide ubiquinone oxidoreductase in complex I of the OXPHOS pathway. The mechanism by which these mutations cause the LHON phenotype is not well understood. ... 

Oxidoreductases catalyze oxidation and reduction reactions that occur within the cell. They are very appealing for industrial uses because of the reactions that they are able to catalyze. However, they often need expensive cofactors such as nicotinamide adenine dinucleotides (e.g., NAD+/NADH) and flavines (e.g., FAD/FADH2) in the reactions. In fact, nicotinamide adenine dinucleotides are required by about 80% of oxidoreductases. Fortunately, several NAD(H)... 

The simplest example of such reactions is the decarboxylation of pyruvate. Both model and enzyme studies have shown the intermediacy of covalent complexes formed between the cofactor and the substrate. Kluger and coworkers have studied extensively the chemical and enzymatic behavior of the pyruvate and acetaldehyde complexes of ThDP (2-lactyl or LThDP, and 2-hydroxyethylThDP or HEThDP, respectively) . As Scheme 1 indicates, the coenzyme catalyzes both nonoxidative and oxidative pathways of pyruvate decarboxylation. The latter reactions are of immense consequence in human physiology. While the oxidation is a complex process, requiring an oxidizing agent (lipoic acid in the a-keto acid dehydrogenases , or flavin adenine dinucleotide, FAD or nicotinamide adenine dinucleotide , NAD " in the a-keto acid oxidases and Fe4.S4 in the pyruvate-ferredoxin oxidoreductase ) in addition to ThDP, it is generally accepted that the enamine is the substrate for the oxidation reactions. 

The mitochondrial respiratory chain is composed of more than 80 proteins grouped into 5 distinct complexes that form an integrated electron transfer chain (ETC, Figure 4). Initiation of electron transport takes place either from complex I (reduced nicotinamide adenine diphosphate (NADH)—ubiquinone oxidor-eductase) or from complex II (succinate—ubiquinone oxidoreductase) to complex III (ubiquinol—cytochrome c oxidoreductase) by ubiquinone (UQ, coenzyme Q, 39). As shown in Scheme 1, ubiquinone is reduced to... 

The MT T assay is another colorimetric method to assess cell viability. NAD(P)H (nicotinamide adenine dinucleotide(P)H)-dependent cellular oxidoreductase enzymes may, under defined conditions, reflect the number of viable cells present. These enzymes are capable of reducing the tetrazolium dye MTT 3-(4,5-diwiethylfhiazol-2-yl)-2,5-diphenylletrazolium bromide to its insoluble purple-coloured formazan (Figure 7.71). In living cells, the originally yellow MTT is converted by cellular reductase to purple formazan (Mosmann, 1983). A solubilisation solution (usually either dimethyl sulfoxide or sodium dodecyl sulfate dissolved in diluted hydrochloric acid) is added to dissolve the insoluble... 

ACP = acyl carrier protein ACPA D = ACPA desat-urase AlkB = octane 1-monooxygenase AOX = alternative oxidase DMQ hydroxylase = 5-demethoxyquinone hydroxylase EXAFS = extended X-ray absorption fine structure spectroscopy FMN = flavin mononucleotide FprA = flavoprotein A (flavo-diiron enzyme homologue) Hr = hemerythrin MCD = magnetic circular dichroism MME hydroxylase = Mg-protophorphyrin IX monomethyl ester hydroxylase MMO = methane monooxygenase MMOH = hydroxylase component of MMO NADH = reduced nicotinamide adenine dinucleotide PAPs = purple acid phosphatases PCET = proton-coupled electron transfer, PTOX = plastid terminal oxidase R2 = ribonucleotide reductase R2 subunit Rbr = rubrerythrin RFQ = rapid freeze-quench RNR = ribonucleotide reductase ROO = rubredoxin oxygen oxidoreductase XylM = xylene monooxygenase. 

Over 250 oxidoreductases (dehydrogenases) use the cosubstrate yS-nicotinamide adenine (phosphate) dinucleotide (NAD(P) ) to oxidize a substrate SHj with concomitant reduction of the cofactor to NAD(P)H. In the most cases the cofactor is bound simultaneously with the substrate in the active site of the enzyme, allowing transfer of a hydride ion from the substrate to NAD(P)-. ... 

Malinauskas, A., Kulys, J. J., Alcohol, Lactate and Glutamate Sensors Based on Oxidoreductases with Regeneration of Nicotinamide Adenine Dinucleotide , Anal. Chim. Acta 98 (1978) 31-37. 

Pyridoxol 210 (pyridoxine, 3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridine, vitamin B6) was formerly known as adermine (Kuhn 1938) because vitamin B5 deficiency causes skin diseases in animals. Pyridoxal (211, R = CHO) and pyridoxamine (211, R = CH2NH2) also belong to the vitamin B group. Pyridoxal phosphate 212 is a coenzyme for many of the enzymes involved in the metabolism of amino acids. Nicotinamide adenine dinucleotide 213 (NAD , reduced form NADH) is a component of oxidoreductases (for its action see p 293, synthesis see p 131). 

Hou, D.X. et al.. Transcriptional regulation of nicotinamide adenine dinucleotide phosphate quinone oxidoreductase in murine hepatoma cells by 6-(methylsulfmyl)hexyl isothiocyanate, an active principle of wasabi (Eutrema wasabi Maxim.), Cancer Lett., 161,195, 2000. 

The alcohol dehydrogenase isolated from horse fiver (LADH) [E.C.l.1.1.1.], MW 80,000, is available as a highly purified, crystalhne material composed of two (or more) isozymes (57), one of which is present in >90%. The general physical and chemical properties of this zinc enz5une have been reviewed by Sund and Theorell (35). This nicotinamide-adenine dinucleotide oxidoreductase catalyzes the aldehyde-alcohol interconversion shown in Eq. (16). 

Oxidoreductase dehydrogenase and flavoenzymes. Nicotinamide adenine dinucleotide (NAD+)/nicotinamide adenine dinucleotide phosphate (NADF) and flavin mononucleotide (FMN)/flavin adenine dinucleotide (FAD) are the two major types of redox coenzymes. 

Oxidoreductases are concerned with oxidation and reduction processes. Dehydrogenases form one type of these and will catalyse the removal of H atoms from a substrate and transfer them to an acceptor. Important hydrogen acceptors are nicotinamide adenine dinucleotide, NAD+, and the closely related nicotinamide adenine dinncleotide phosphate, NADP (12.23). Lactic dehydrogenase catalyses the transfer of hydrogen from lactic acid which gives pyruvic acid and converts NAD+ into the rednced form NADH (12.25). 

The third number in the series serves to allocate the enzyme to a sub-subclass. For oxidoreductase enzymes, this third number shows the type of acceptor involved [e.g. 1 denotes a co-enzyme, such as nicotinamide-adenine dinucleotide phosphate (NADP) 2 denotes a cytochrome 3 denotes molecular oxygen]. For the transferases, the third number allows a subdivision of the type of group transferred (thus the C, unit can be defined as methyl or carboxyl, etc.). For the hydrolases, the lyases, the isomerases, and the ligases, the third number shows more precisely the... 

Nicotinamide adenine dinucleotide (NAD+) and its derivative NADP+, which has an additional phosphate group esterified at the C-2 hydroxyl group of the ribose moiety of the adenine portion of the molecule, are coenzymes or co-substrates of oxidoreductases (C 2.1). Though nicotinic acid and nicotinamide can be synthesized in animals and human beings, they are vitamins for men living on a special diet, e.g., on corn as main nutrient (E 2.1). 

The example of the reversible oxidation of ethanol (CH3CH2OH) to ethanal (acetaldehyde, CH3CHO) by yeast alcohol dehydrogenase (alcohol NAD " oxidore-ductase [EC 1.1.1.1]) is one such (now classical) process and is discussed below. The oxidoreductase uses nicotinamide adenine dinucleotide (NAD") (oxidized form) as its coenzyme, and it is in the pyridine (azabenzene, C5H5N) ring that the reduction is clearly seen. 

---