Metabolism adenine nucleotides

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 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 ... 

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. 

Adenosine Triphosphate Adenosine 5 -(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH]... 

This is a complex molecule, made up of an adenine nucleotide (ADP-3 -phosphate), pantothenic acid (vitamin B5), and cysteamine (2-mercaptoethylamine), but for mechanism purposes can be thought of as a simple thiol, HSCoA. Pre-eminent amongst the biochemical thioesters is the thioester of acetic acid, acetyl-coenzyme A (acetyl-CoA). This compound plays a key role in the biosynthesis and metabolism of fatty acids (see Sections 15.4 and 15.5), as well as being a building block for the biosynthesis of a wide range of natural products, such as phenols and macrolide antibiotics (see Box 10.4). 

An index of the phospho anhydride (i.e.,P—O—P) bond content of the adenine nucleotides of a cell, based on a hypothetical modeP that attempts to explain the metabolic basis for control of ATP utilization and regeneration. Later studies demonstrated that the energy charge model is overly simplistic and that its principles are unlikely to constitute a useful model for the control of energy metabolism within biological systems. 

Free purine and pyrimidine bases are constantly released in cells during the metabolic degradation of nucleotides. Free purines are in large part salvaged and reused to make nucleotides, in a pathway much simpler than the de novo synthesis of purine nucleotides described earlier. One of the primary salvage pathways consists of a single reaction catalyzed by adenosine phosphoribosyltransferase, in which free adenine reacts with PRPP to yield the corresponding adenine nucleotide ... 

Several of the B vitamins function as coenzymes or as precursors of coenzymes some of these have been mentioned previously. Nicotinamide adenine dinucleotide (NAD) which, in conjunction with the enzyme alcohol dehydrogenase, oxidizes ethanol to ethanal (Section 15-6C), also is the oxidant in the citric acid cycle (Section 20-10B). The precursor to NAD is the B vitamin, niacin or nicotinic acid (Section 23-2). Riboflavin (vitamin B2) is a precursor of flavin adenine nucleotide FAD, a coenzyme in redox processes rather like NAD (Section 15-6C). Another example of a coenzyme is pyri-doxal (vitamin B6), mentioned in connection with the deamination and decarboxylation of amino acids (Section 25-5C). Yet another is coenzyme A (CoASH), which is essential for metabolism and biosynthesis (Sections 18-8F, 20-10B, and 30-5A). 

A quantitative description of oxidative phosphorylation within the cellular environment can be obtained on the basis of nonequilibrium thermodynamics. For this we consider the simple and purely phenomenological scheme depicted in Fig. 1. The input potential X0 applied to the converter is the redox potential of the respiratory substrates produced in intermediary metabolism. The input flow J0 conjugate to the input force X0 is the net rate of oxygen consumption. The input potential is converted into the output potential Xp which is the phosphate potential Xp = -[AG hoS -I- RT ln(ATP/ADP P,)]. The output flow Jp conjugate to the output force Xp is the net rate of ATP synthesis. The ATP produced by the converter is used to drive the ATP-utilizing reactions in the cell which are summarized by the load conductance L,. Since the net flows of ATP are large in comparison to the total adenine nucleotide pool to be turned over in the cell, the flow Jp is essentially conservative. 

On these theoretical curves two sets of experimental data are inserted the cytosolic adenine nucleotide concentrations measured in livers from fed rats (F) and starved rats (H).5 In the livers of the fed rats the degree of coupling is astonishingly close to cfif (Table I). These livers have been regarded to be in a metabolic resting state. 7 Hence, for the metabolic resting state, the maximization of the economic output power seems to be of importance. In contrast, in the livers from starved rats the degree... 

Nucleotides play important roles in all major aspects of metabolism. ATP, an adenine nucleotide, is the major substance used by all organisms for the transfer of chemical energy from energy-yielding reactions to energy-requiring reactions such as biosynthesis. Other nucleotides are activated intermediates in the synthesis of carbohydrates, lipids, proteins, and nucleic acids. Adenine nucleotides are components of many major coenzymes, such as NAD+, NADP+, FAD, and CoA. (See chapter 10 for structures of these coenzymes.)... 

The levels of extracellular adenosine could increase step-wise up to micromolar levels as the outcome of the transport and/or diffusion of intracellular adenosine, formed from the large pools of intracellular ATP in hypoxic conditions (Sitkovsky et al. 2005,2008). Hypoxia can upregulate an adenine nucleotide-metabolizing ecto-enzyme cascade comprising ecto-ATP apyrase (CD39) and CD73 (Synnestvedt et al. 2002). 

The control of the respiration process and ATP synthesis shifts as the metabolic state of the mitochondria changes. In an isolated mitochondrion, control over the respiration process in state 4 is mainly due to the proton leak through the mitochondrial inner membrane. This type of control decreases from state 4 to state 3, while the control by the adenine nucleotide and the dicarboxylate carriers, cytochrome oxidase, increases. ATP utilizing reactions and transport activities also increase. Therefore, in state 3, most of the control is due to respiratory chain and substrate transport. 

Bossard P. and Karl D. M. (1986) The direct measurement of ATP and adenine nucleotide pool turnover in microorganisms a new method for environmental assessment of metabolism, energy flux and phosphorus dynamics. J. Plankton Res. 8, 1-13. 

The mitochondrial translocators which have been most carefully assessed with respect to their role in control of metabolism are (1) the adenine nucleotide translocator with respect to its role in the control of respiration (2) the liver pyruvate transporter and the control of gluconeogenesis and (3) kidney glutamate and glutamine transport and their control of ammoniagenesis. 

From these studies and those of Tager, an intermediate view is emerging with respect to the role of the adenine nucleotide translocator in the control of mitochondrial respiration. This view suggests that a variable degree of control is exerted depending upon the metabolic state, substrate availability, etc., such that control may be considerable or minimal. Such a view also implies that the control strength may vary from tissue to tissue and from cell to cell within the tissue. 

Nees, S and Gerlach, E, Adenine nucleotide and adenosine metabolism in cultured coronary endothelial cells. In Regulatory functions of adenosine, (eds. Berne, RM, Rail, TW and Rubio, R), Martinus Nijhoff Publishers, The Hague, 1983,347-360. 

Nees, S, Dendorfer, A, New perspectives of myocardial adenine nucleotide metabolism. In Role of adenosine and adenine nucleotides in the biological system, (eds Itiui, S and Nakazawa, M), Elsevier Science Publishers, Amsterdam, 1991,273-288. 

Anita Ryningen has done research since 1991 until the present on signaling mechanisms involved in activation and inhibition of platelet responses at the Department of Biochemistay and Molecular Biology, University of Bergen. She is currendy finaliTing her Ph. D. thesis. Holm Holmsen is Professor at the same institution and received his Dr. Phil, from the University of Oslo in 1969 on adenine nucleotide metabolism in platelets. He continued these studies at the Department of Medicine, Temple University Medical School, Philadelphia (1970-1982). His current research interest is lipid-mediated, cellular signal transduction. 

HOLMSEN H, SeTKOWSKY CA, Day HJ. Effects of antimycin and 2-deoxygIucose on adenine nucleotides in human platelets. Role of metabolic adenosine trisphosphate in primary aggregation, secondary aggregation and shape change in platelets. BiodiemJ 44 385-396,1974. 

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