Nucleotide, adenine

The adenine nucleotides (AMP, ADP, and ATP) comprise a family of cofactors which are of prime importance in the transport of phosphate. The importance of phosphate as a means of transforming chemical potential and oxidation energy into metabolically active forms has been amply discussed by Lipmann and by Kalckar and others and needs no elaboration here. The major role of the adenine nucleotide system is the transport and storage of phosphate bond energy. 

In a recent review, Colowick has admirably discussed the role of the adenine nucleotides in various transphosphorylation reactions, and a thorough consideration is given to the enzymes involved. Only the more general aspects of the problem will therefore be discussed. 

The adenine nucleotide system consists of the following members adenosine 5 -phosphoric acid (AMP), adenosine diphosphoric acid (ADP), and adenosine triphosphoric acid (ATP). The structures of these compounds are given in Fig. 5. These structures have been confirmed by the classical chemical synthesis of Todd and his co-workers.  

The nucleotides are interconvertible by the enzyme myokinase which catalyzes the following transformation  

Colowick, in Sumner and Myrback, The Enzymes, Academic Press, New York, 1951, Vol. II, Part 1, p. 114. 

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Figure 11.39 summarizes the reactions taking place in this amperometric sensor. FAD is the oxidized form of flavin adenine nucleotide (the active site of the enzyme glucose oxidase), and FAD1T2 is the active site s reduced form. Note that O2 serves as a mediator, carrying electrons to the electrode. Other mediators, such as Fe(CN)6 , can be used in place of O2. 

The overall direction of the reaction will be determined by the relative concentrations of ATP, ADP, Cr, and CrP and the equilibrium constant for the reaction. The enzyme can be considered to have two sites for substrate (or product) binding an adenine nucleotide site, where ATP or ADP binds, and a creatine site, where Cr or CrP is bound. In such a mechanism, ATP and ADP compete for binding at their unique site, while Cr and CrP compete at the specific Cr-, CrP-binding site. Note that no modified enzyme form (E ), such as an E-PO4 intermediate, appears here. The reaction is characterized by rapid and reversible binary ES complex formation, followed by addition of the remaining substrate, and the rate-determining reaction taking place within the ternary complex. 

Several classes of vitamins are related to, or are precursors of, coenzymes that contain adenine nucleotides as part of their structure. These coenzymes include the flavin dinucleotides, the pyridine dinucleotides, and coenzyme A. The adenine nucleotide portion of these coenzymes does not participate actively in the reactions of these coenzymes rather, it enables the proper enzymes to recognize the coenzyme. Specifically, the adenine nucleotide greatly increases both the affinity and the speeifieity of the coenzyme for its site on the enzyme, owing to its numerous sites for hydrogen bonding, and also the hydrophobic and ionic bonding possibilities it brings to the coenzyme structure. 

Pantothenic acid, sometimes called vitamin B3, is a vitamin that makes up one part of a complex coenzyme called coenzyme A (CoA) (Figure 18.23). Pantothenic acid is also a constituent of acyl carrier proteins. Coenzyme A consists of 3, 5 -adenosine bisphosphate joined to 4-phosphopantetheine in a phosphoric anhydride linkage. Phosphopantetheine in turn consists of three parts /3-mercaptoethylamine linked to /3-alanine, which makes an amide bond with a branched-chain dihydroxy acid. As was the case for the nicotinamide and flavin coenzymes, the adenine nucleotide moiety of CoA acts as a recognition site, increasing the affinity and specificity of CoA binding to its enzymes. 

Further computational studies on adenines and adenosines concern the reaction mechanism of ribonuclease A with cytidyl-3,5 -adenosine [99BP697] and the molecular recognition of modified adenine nucleotides [99JMC5338]. 

Thus ATP is the effective controller of metabolism but because AMP + ADP + ATP is constant, it is really the ratio of adenine nucleotides which is important This ratio is termed die adenylate charge or energy charge and is expressed as ... 

In relation to separation of nucleotides, Hoffman61 found that adenine nucleotides interacted most strongly with cycloheptaamylose, presumably by inclusion of the base within the cavity of cyclodextrin. When epichlorohydrin-cross-linked cycloheptaamylose gel was used as a stationary phase for nucleic acid chromatography, adenine-containing compounds were retarded most strongly. 

The fact that adenosine and its derivatives are azo coupling components is used for immobilizing nicotinamide-adenine nucleotide (NAD+) for affinity chromatography purposes. In 12.58 NAD+ is bonded to a matrix through an azo bond. Compound 12.58 is used for the purification of dehydrogenase enzymes (Hocking and Harris, 1973). 

Naphthoquinone diazides 32, 284ff., see also Quinone diazides 2,3-Naphthotriazole, formation 132 f. Negations, psycholinguistics of 215 Nesmeyanov reactions 273 ff. Nicotinamide-adenine nucleotide (NAD+) 328 f. 

Adenine nucleotides Phosphate (P7) Dicarboxylates/P " exchange 2-Oxoglutarate/malate exchange Pyruvate... 

Complex V 370 kDa About 16 3 bound adenine nucleotides Base (FJ spans membrane, connected to F, on inner face 0.52-0.54 Translocates protons across membrane, is associated with ATP synthesis, or with ATP hydrolysis... 

In both intermediate and maximum rates of respiration, control is distributed between several different steps, including the activity of the adenine nucleotide translocator (Groen et al., 1983). It is now recognized that the idea of a simple rate-limiting step for a metabolic pathway is simplistic and that control is shared by all steps although to different extents (Kacserand Bums, 1978 Fell, 1992). Each step in a pathway has a flux control coefficient (FCC) defined as ... 

Figure 10-8. Phosphate cycles and interchange of adenine nucleotides.

A combination of the above reactions makes it possible for phosphate to be recycled and the adenine nucleotides to interchange (Figure 10-8). 

Figure 12-11. Combination of phosphate transporter ( ) with the adenine nucleotide transporter ((2)) in ATP synthesis. The H+ZP, symport shown is equivalent to the P /OH antiport shown in Figure 12-10. Four protons are taken into the mitochondrion for each ATP exported. However, one less proton would be taken in when ATP is used inside the mitochondrion.

The terms first, second, and third nucleotide refer to the individual nucleotides of a triplet codon. U, uridine nucleotide C, cytosine nucleotide A, adenine nucleotide G, guanine nucleotide Term, chain terminator codon. AUG, which codes for Met, serves as the initiator codon in mammalian cells and encodes for internal methionines in a protein. (Abbreviations of amino acids are explained in Chapter 3.)... 

The second B. thuringiensis toxin, the /3-exotoxin has a much broader spectrum encompassing the Lepidoptera, Coleoptera and Diptera. It is an adenine nucleotide, probably an ATP analogue which acts by competitively inhibiting enzymes which catalyse the hydrolysis of ATP and pyrophosphate. This compound, however, is toxic when administered to mammals so that commercial preparations of the B. thuringiensis 5-endotoxin are obtained from strains which do not produce the j8-exotoxin. 

Buhl, M.R. and Jorgensen, S. (1975). Breakdown of 5 -adenine nucleotides in ischaemic renal cortex estimated by oxypurine excretion during perfusion. Scand. J. Clin. Lab. Invest. 35, 211-217. 

Faller, J. and Fox, I.H. (1982). Ethanol-induced hyperuricaemia. Evidence for increased urate production by activation of adenine nucleotide turnover. N. Engl. J. Med. 307, 1598-1602. 

Tirmenstein, M.A. and Nelson, S.D. (1990). Acetaminophen-induced oxidation of protein thiols contribution of impaired thiol metabolizing enzymes and the breakdown of adenine nucleotides. J. Biol. Chem. 2265, 3059-3065. 

Seasonal variations in the metabolic fate of adenine nucleotides prelabelled with [8—1-4C] adenine were examined in leaf disks prepared at 1-month intervals, over the course of 1 year, from the shoots of tea plants (Camellia sinensis L. cv. Yabukita) which were growing under natural field conditions by Fujimori et al.33 Incorporation of radioactivity into nucleic acids and catabolites of purine nucleotides was found throughout the experimental period, but incorporation into theobromine and caffeine was found only in the young leaves harvested from April to June. Methy-lation of xanthosine, 7-methylxanthine, and theobromine was catalyzed by gel-filtered leaf extracts from young shoots (April to June), but the reactions could not be detected in extracts from leaves in which no synthesis of caffeine was observed in vivo. By contrast, the activity of 5-phosphoribosyl-1-pyrophosphate synthetase was still found in leaves harvested in July and August. 

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