Coenzymes adenosine dinucleotide phosphate

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. 

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. 

Whereas catabolism involves oxidation of starting molecnles, biosynthesis or anabolism involves reduction reactions, hence the need for a reducing agent or hydrogen donor, which is usually NADP (nicotinamide adenine dinucleotide phosphate). These catalysts are known as coenzymes and the most widely occurring is coenzyme A (CoA), made up of ADP (adenosine diphosphate) and pantetheine phosphate. 

Abbreviations used are PP-ribose-P, a-5-phosphoribosyl-1-pyrophosphate PRA, 3-5-phosphoribosyl-l-amine GAR, glycinamide-ribonucleotide formyl-GAR, a-formyl-GAR formyl-GAM, a-formyl gly-cinamidineribonucleotide IMP, inosine 5 -monophosphate AMP, adenosine 5 -monophosphate GMP, guanosine 5 -monophosphate PPi, inorganic pyrophosphate CoA-SH, reduced coenzyme A NADP, nicotinamide adenine dinucleotide phosphate PRT, hypoxanthine-guanine phosphoribosyltransferase. 

The coenzymes nicotinamide-adenine dinucleotide (NAD) and nicotinamide - adenine dinucleotide phosphate (NADP), their reduced forms, and adenosine 5 -monophosphate (5 -AMP) and adenosine 2, 5 -diphosphate (2. 5 -ADP) represent well-known examples of this class. They can be considered for the purification of ca. 25 % of the known enzymes (especially dehydrogenases). 

A cofactor is a non-protein chemical compound that is required for an enzyme s biological activity. It can be considered as a helper molecule that assists in biochemical transformations. Cofactors can be classified into two groups organic cofactors, such as nicotinamide adenine dinucleotide phosphate (NADP), nicotinamide adenine dinucleotide (NAD), flavin adenine dinucleotide (FAD), adenosine triphosphate (ATP), quinone compounds, and coenzyme A (CoA), and inorganic cofactors, such as metal ions and iron-sulfur clusters. Because some organic cofactors are too costly to refurnish by frequent addition, it is vital to regenerate them in vitro. NADPH from NADP can be regenerated with various chemical, enzymatic, and electrochemical... 

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).

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... 

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.

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. 

The nucleotide coenzymes are structurally related to the mononucleotides. Typical nucleotide coenzymes are adenosine triphosphate (ATP), flavin-adenine-dinucleotide (FAD) and numerous other phosphate esters of complex structure, containing adenosine, guanosine, cytidine or uridine. Five coenzymes are known for example, which are derived from cytidine diphosphate (CDP) CDP-choline, CDP-ethanolamine, CDP-diglyceride, CDP-glycerol and CDP-ribitol. 

The following abbreviations will be used in this article. ATP = adenosine triphosphate ADP — adenosine diphosphate DPNox oxidized diphosphopyri-dine nucleotide DPNred = reduced diphosphopyridine nucleotide CoA or CoA—SH = coenzyme A CoA—S—COCH3 = acetyl-coenzyme A FAD = flavin adenine dinucleotide R—P = low-energy phosphate bond R P = high-energy bond Pi = inorganic orthophosphate. 

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