Adenosine-2 ,5-diphosphate from coenzyme

Nucleosides are also encountered in the structures of adenosine triphosphate (ATP) and coenzyme A (HSCoA). ATP provides nature with its currency unit for energy. Hydrolysis of ATP to adenosine diphosphate (ADP) liberates energy, which can be coupled to energy-requiring processes in biochemistry, and synthesis of ATP from ADP can be coupled to energy-releasing processes (see Box 7.25). 

The section of the molecule discussed so far represents a functional unit. In the cell, it is produced from pantothenate. The molecule also occurs in a protein-bound form as 4 -phosphopantetheine in the enzyme fatty acid synthase (see p. 168). In coenzyme A, however, it is bound to 3, 5 -adenosine diphosphate. 

Energy from fuel oxidation is converted to the high-energy phosphate bonds of adenosine triphosphate (ATP) by the process of oxidative phosphorylation. Most of the energy from oxidation of fuels in the TCA cycle and other pathways is conserved in the form of the reduced electron-accepting coenzymes, NADH and FAD(2H). The electron transport chain oxidizes NADH and FAD(2H), and donates the electrons to O2, which is reduced to H2O (Fig. 21.1). Energy from reduction 0/O2 is used for phosphorylation of adenosine diphosphate (ADP) to ATP by ATP synthase (FgFjATPase). The net yield of oxidative phosphorylation is approximately 2.5 moles of ATP per mole of NADH oxidized, or 1.5 moles of ATP per mole of FAD(2H) oxidized. 

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. 

It appears that most nucleotide pyrophoqihatases from mammalian tissues cleave the reduced forms of the coenzymes faster than the oxidized nucleotides. The plant nucleotide pyrophosphatases, however, q>lit DPNH, TPNH, and the oxidized coenzyme forms at equal rates. It should be pointed out, however, that an enzyme such as the potato nucleotide pyrophosphatase also attacks ATP and adenosine diphosphate (ADP), whereas the purified pigeon liver enzyme does not. The snake venom enzyme seems to split the oxidized and reduced nucleotide at equal rates. 

FIGURE 18.6 The coenzyme NAD (nicotinamide adenine dinucleotide), which consists of a nicotinamide portion from the vitamin niacin, ribose, and adenosine diphosphate, is reduced to NADH -F H+. 

FIGURE 18.8 Coenzyme A is derived from a phosphorylated adenosine diphosphate (ADP) and pantothenic acid bonded by an amide bond to aminoethanethiol, which contains the — SH reactive part of the molecule. 

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...

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. ... 

The presence of two coenzyme-binding sites is unexpected since they cannot be inferred solely from the crystal structure of CPR. Kinetic studies with wild t) e and W676H CPR at different concentrations of NADPH have, however, provided further support for the existence of two sites The rate of flavin reduction in the isolated FAD domain and CPR increases as NADPH is decreased from molar excess to stoichiometric concentrations. At stoichiometric concentration, the second noncatalytic site is predominantly vacant and the partial inhibition on the rate of flavin reduction from the catalytic site is therefore relieved (Figure 4.9). Occupation of the noncatalytic site occurs at NADPH concentrations in excess of the enzyme concentration, and impairs NADP" " release from the catalytic site. This in turn partially inhibits flavin reduction, the rate of which is gated by NADP release. Preincubation of the enzyme with a stoichiometric amount of adenosine 2, 5 -diphosphate does not lead to inhibition of the flavin reduction rate. We infer that the binding of adenosine 2, 5 -diphosphate prevents NADPH from binding to the noncatalytic site. This observation also suggests that it is the nicotinamide-ribose-phosphate portion of NADPH bound at the second site that hinders NADP" release from the catalytic site. Clearly, these new... 

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. 

In addition to their role as components of nucleoproteins, purines and pyrimidines are vital to the proper functioning of the cell. The bases are constituents of various coenzymes, such as coenzyme A (CoA), adenosine triphosphate (ATP), guanosine triphosphate (GTP), cytidine triphosphate (CTP), diphosphopyridine nucleotide (DPN), triphosphopyridine nucleotide (TPN), and flavin adenine dinucleotide (FAD). A pyrimidine derivative, cytidine diphosphate choline, is involved in phospholipid synthe another pyrimidine compound, uridine diphosphate glucose, is an important substance in carbohydrate metabolism. Cytidine diphosphate ribitol functions in the biosynthesis of a new group of bacterial cell-wall components, the teichoic acids. While mammals excrete nitrogen derived from protein catabolism in the form of urea, birds eliminate their nitrogen by synthesizing it into the purine compound, uric acid. 

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