Coenzymes adenosine dinucleotide

The extreme selectivity of enzymatic reactions can be utiUzed best with enzymes catalysing electron exchange. Such enzymes are oxidases and dehydrogenases. The former catalyse redox reactions including oxygen [Eq. (7.21)], the latter such reactions with the participation of the coenzyme nicotinamide adenosine dinucleotide (NAD). Considering the oxidized form NAD" ", or the reduced form NADH, the general Eq. (7.22) is obtained ... 

Coenzymes such as adenosine diphosphate (ADP), adenosine SGtriphosphate (ATP), nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide, reduced (NADH), are involved in some reactions (4). 

Catalysis by flavoenzymes has been reviewed and various analogues of FAD have been prepared e.g. P -adenosine-P -riboflavin triphosphate and flavin-nicotinamide dinucleotide ) which show little enzymic activity. The kinetic constants of the interaction between nicotinamide-4-methyl-5-acetylimidazole dinucleotide (39) and lactic dehydrogenase suggest the presence of an anionic group near the adenine residue at the coenzyme binding site of the enzyme. ... 

Figure 6.1 Pathways involved in glucose oxidation by plant cells (a) glycolysis, (b) Krebs cycle, (c) mitochondrial cytochrome chain. Under anoxic conditions. Reactions 1, 2 and 3 of glycolysis are catalysed by lactate dehydrogenase, pyruvate decarboxylase and alcohol dehydrogenase, respectively. ATP and ADP, adenosine tri- and diphosphate NAD and NADHa, oxidized and reduced forms of nicotinamide adenine dinucleotide PGA, phosphoglyceraldehyde PEP, phosphoenolpyruvate Acetyl-CoA, acetyl coenzyme A FP, flavoprotein cyt, cytochrome e, electron. (Modified from Fitter and Hay, 2002). Reprinted with permission from Elsevier...

Fig. 1. Energy metabolism in the normal myocardium (ATP adenosine-5 -triphosphate, ADP adenosine-5 -diphosphate, P phosphate, PDH pyruvate dehydrogenase complex, acetyl-CoA acetyl-coenzyme A, NADH and NAD" nicotinamide adenine dinucleotide (reduced and oxidized), FADH2 and FAD flavin adenine dinucleotide (reduced and oxidized).

In addition to their role in the formation of DNA and RNA (see Section 27.2), nucleotides have other important biological functions. For example, adenosine triphosphate (ATP) is an important energy carrier in biochemical reactions, and nicotinamide adenine dinucleotide is a coenzyme that is often involved in biochemical oxidation-reduction reactions. 

Specific nucleotide recognition in the ternary complex between the enzyme lactate dehydrogenase and the modified coenzyme NAD+-pyruvate (NAD = nicotinamide-adenine-dinucleotide). NAD+ consists of two nucleotides, adenosine-5 -phosphate and nicotinamide ribose-5 -phosphate, which are linked through a pyrophosphate bond. 

Subsequently, the functions of the vitamin were better established and requirements for the vitamin were set. Riboflavin is an Integral part of two coenzymes, flavin-5 -phosphate (FMN) and flavin adenine dinucleotide (FAD), which function in oxidation/reductlon reactions. Indeed, riboflavin is an enzyme cofactor which is necessary in metabolic processes in which oxidation of glucose or fatty acid is used for production of adenosine triphosphate (ATP) as well as in reactions in which oxidation of amino acids is accomplished. The minimum requirement for riboflavin has been established as that amount which actually prevents the signs of deficiency. A range of intakes varying from 0.55 to 0.75 mg/day of riboflavin has been established as the minimum amount which is required to prevent appearance of deficiency signs. 

Inactivation of alcohol dehydrogenase from yeast with 14C-labeled [3-(3-bromoacetylpyridinio)-propyl]-adenosine pyrophosphate followed by oxidation showed the presence of 1-carboxymethyl histidine66. After inactivation of the enzyme with labeled [3-(4-bromoacetylpyridinio)-propyl]-adenosine pyrophosphate followed by oxidation, S-carboxymethyl cysteine was identified in the protein. In the case of glyceraldehyde-3-phosphate dehydrogenase, treatment with either coenzyme analogue leads to the modification of the cysteine residue. Treatment with [14C]nicotinamide-5-bromo-4-methylimidazole dinucleotide did not reveal any modified amino-acid-residues. The labeled nicotinamide residue split off during the recovery of the inactivated enzyme. Attempts to synthesize an inactivator labeled with a 14C-acetyl residue did not give satisfactory yields. If the enzyme-coenzyme derivative was treated with tritiated sodium boron hydride, tritium could be introduced (Fig. 22). Studies with... 

Nucleoside 2 (or 3 ),5 -diphosphates have been isolated by degradation of certain coenzymes, as well as from hydrolyzates of nucleic acids. Adenosine 3, 5 -diphosphate (see p. 320) has been isolated by enzymic hydrolysis of coenzyme A and from active sulfate (adenosine 3 -phosphate 5 -phosphosulfate). Adenosine 2, 5 -diphosphate was shown to be present in the adenylic acid moiety of the coenzyme adenine-nicotinamide dinucleotide phosphate which, by treatment with a 5 -nucleotidase from potatoes, is converted into adenosine 2 -phosphate. Adenosine 3, 5 -di-phosphate is reported to play a role as a cofactor in the bioluminescence of Renilla reniformis (pansy) Ribonucleic acid carrying a terminal 5 -phos-phate group yields ribonucleoside 3, 5 -diphosphates on digestion with phosphoesterases. ... 

Nitrosyl chloride in iV,iV-dimethylfonnamide at low temperature has been used for the convenient deamination of adenosine, adenosine 5 -phosphate, adenosine 5 -triphosphate, and their iV -oxides to the corresponding inosine derivatives. Nitrous anhydride (N2O3) has been used to convert the coenzyme adenine-nicotinamide dinucleotide into hypo-xanthine-nicotinic acid dinucleotide. 

Scheme 22 The whole biosynthetic pathway of sugar nucleotides. ATP, adenosine triphosphate Gal-1 -P, galactose-1-phosphate UTP, uridine triphosphate UDP, uridine diphosphate NAD, nicotinamide adenine dinucleotide Fru, fructose AcCoA, acetyl coenzyme-A PEP, phosphoenolpyruvate CTP, cytidine triphosphate NADP, nicotinamide adenine dinucieotide phosphate GTP, guanosine triphosphate.

Studies of dinucleotides as coenzyme analogs for YADH and LADH have been discussed in Section II,G. Fragments of the coenzyme molecule are inhibitors to YADH, competitive to the coenzyme [1 14,802,435-437). The participation of the pyrophosphate moiety in coenzyme binding to YADH has been questioned since free pyrophosphate is not an inhibitor [1,435). Furthermore, a smaller inhibition constant has been found for adenosine than for AMP and ADP [214). On the other hand, AMP and ADP inhibit the enzyme at low pH, whereas adenosine has no effect [437). Evidence for possible interaction between the pyrophosphate moiety and arginine residues in YADH is discussed in Section III,C,3. 

One mechanism that has been proposed to explain the hepatotoxicity of 1,1,2-trichloroethane is the generation of free radical intermediates from reactive metabolites of 1,1,2-trichloroethane (acyl chlorides). Free radicals may stimulate lipid peroxidation which, in turn, may induce liver injury (Albano et al. 1985). However, Klaassen and Plaa (1969) found no evidence of lipid peroxidation in rats given near-lethal doses of 1,1,2-trichloroethane by intraperitoneal injection. Takano and Miyazaki (1982) determined that 1,1,2-trichloroethane inhibits intracellular respiration by blocking the electron transport system from reduced nicotinamide adenine dinucleotide (NADH) to coenzyme Q (CoQ), which would deprive the cell of energy required to phosphorylate adenosine diphosphate (ADP) and thereby lead to depletion of energy stores. 

A major coenzyme of redox enzymes is nicotinamide adenine dinucleotide (NAD) (Table 2). The cofactor is composed of an adenosine monophosphate residue linked by a phosphodiester to a 5-phosphoribosyl-l-nicotinamide. 

The Krebs cycle takes two molecules of acetyl coenzyme A from the transition cycle and converts them into four molecules of carbon dioxide (4 CO2), six molecules of reduced nicotinamide adenine dinucleotide (6 NADH), two molecules of reduced flavin adenine dinucleotide (2 FADH2), and two molecules of adenosine triphosphate (2 ATP). 

Coenzyme form(s). FMN (flavin mononucleotide, riboflavin monophosphate), FAD (flavin adenine dinucleotide, riboflavin adenosine diphosphate). 

Abb. HSCoA = Coenzyme A GSH = Glutathione AM(D)(T)P = Adenosine mono (di)(tri)phosphate TPP = Thiamin pyrophosphate LipSj = Lipoic acid amide GD(T)P = Guanosine di(tri)phosphate K = Inorganic phosphate FAD(H2) = Enzyme-bound oxidized (reduced) Flavin-adenine-dinudeotide NAD (H) = Oxidized (reduced) Nicotinamide-adenine-dinucleotide. Compounds with are competitive inhibitors. 

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