Nucleotides in energy metabolism

In view of the central role of the nicotinamide nucleotides in energy-yielding metabolism, and the fact that, at least in theory, the nicotinamide released by ADP-ribosyltransferase (Section 8.4.2) and poly(ADP-ribose) polymerase (Section 8.4.3) is available to be reutilized for nucleotide synthesis (although this may not occur when these enzymes are significantly activated), niacin requirements are conventionally calculated on the basis of energy expenditure. 

It IS intriguing to note that, although all of the nucleotide triphosphates are energetically equivalent, ATP is nonetheless the primary cellular energy carrier. In addition, two important electron carriers, NAD and FAD, are derivatives of ATP. The role oj ATP in energy metabolism is paramowH. 

Intracellular nucleotides play an important role in enzyme and ion channel regulation as well as in energy metabolism and nucleic acid synthesis. There is now widespread appreciation that ATP (and other nucleotides) may so be released into the extracellular fluid by exocytosis from nerve terminals or secretory cells. Thus, extracellular ATP can act as a neurotransmitter or modulator in a variety of peripheral tissues and cells, in autonomic ganglia and in the central nervous system [1-3]. The responses to extracellular ATP are mediated via membrane-bound receptors, termed P2-purinoceptors. Evidence has accumulated indicating heterogeneity of P2-purinoceptors, and it has become apparent that ATP acts on at least five P2-purinoceptor subtypes, i.e. P2X> P2Y> P2U> 2T 2Z... 

The essential elements of Table 2.1 meet these demands. In all cases they are components of the metabolic system in cell or of important final products for example, cellulose for the upright standing of the plant. The function as constituents of such compounds is clear for C, H, and O. These three elements are together components of nearly all organic compounds in the plant [only hydrocarbons (e.g., carotins) are free of O], and therefore they build up the planfs shape. A similarly clear situation holds true for N and P, both of which are constituents of the information carriers DNA and RNA. N is a component of their purine and pyrimidine bases, while phosphoric acid esters of D-ribose or 2-deoxy-D-ribose form the backbone of their nucleotide sequences. Moreover, P plays a very important role in energy metabolism, the key compounds being nucleotide phosphates (e.g., adenosine triphosphate, ATP) (see Scheme 2.1) and the homologous molecules... 

The mineral nutrient elements take part in many processes. Interestingly enough, most elements are involved simultaneously in different reactions of metabolism. Thus, P, K, Mg, Ca, and B are important for the formation of nucleic acids, production of nucleotide phosphates, energy metabolism, and stabilization of membrane structures. Zn is a component of many different enzyme processes, and even Mn and Fe are involved in various reactions. Therefore, no clear assignment of individual elements to distinct areas of metabolism is possible. Indeed, results obtained with different vege-... 

The ready reversibility of the kinases and their abundance in cells has the result that all of the free nucleoside phosphates in a cell reflect the relative amounts of the adenosine phosphates in each of the three levels of phosphorylation. Because the adenosine phosphates are primarily involved in energy metabolism, the energy status of the cell is reflected in the relative amounts of ATP, ADP, and adenylate. Through the very facile transphosphorylation reactions, other nucleoside phosphates become similarly distributed among the three levels of phosphorylation perturbations in energy metabolism, such as those caused by substrate deprivation or by anoxia, cause parallel shifts in the relative amounts of the mono-, di-, and triphosphates in all of the nucleotide families. 

Interstitial nucleotides are derived from intracellular sources. In addition to its central role in cellular energy metabolism, ATP is a classical neurotransmitter that is packaged into secretory granules of neurons and adrenal chromafin cells and released in quanta in response to... 

The fact that many agents which interrupt the synthesis of pyrimidine nucleotides from orotic acid in animals can also inhibit the growth of experimental neoplasms suggests a search for additional antimetabolites whose locus of action is in this metabolic sequence. Two in vitro biological screening systems were developed for this purpose [202—207]. From a study of systems with oxidative energy sources, 5-bromo-[208—209] (Villa), 5-chloro-[210] (Vlllb) and 5-diazo-orotic acid [211] (IX) were found to inhibit the conversion of orotic acid to the uridine nucleotides by 40—100 per cent [202]. 

Nucleotides have a variety of roles in cellular metabolism. They are the energy currency in metabolic transactions, the essential chemical links in the response of cells to hormones and other extracellular stimuli, and the structural components of an array of enzyme cofactors and metabolic intermediates. And, last but certainly not least, they are the constituents of nucleic acids deoxyribonucleic acid (DNA) and ribonucleic acid (ENA), the molecular repositories of genetic information. The structure of every protein, and ultimately of every biomolecule and cellular component, is a product of information programmed into the nucleotide sequence of a cell s nucleic acids. The ability to store and transmit genetic information from one generation to the next is a fundamental condition for life. 

These oxidation reactions employing pyridine nucleotides and flavoproteins are especially important in primary metabolism in liberating energy from fuel molecules in the form of ATP. The reduced coenzymes formed in the process are normally reoxidized via the electron transport chain... 

There are also changes in the rates of metabolism as red blood cells appear and aerobic processes intensify (Lasker and Theilacker, 1962 Laurence, 1975 Timeyko and Novikov, 1991) during the early phases of ontogenesis. Oxygen consumption increases, as do the number of mitochondria and their protein contents (Abramova and Vasilyeva, 1973 Ozemyuk, 1993). The adenyl nucleotide pool (ATP and ADP) decreases (Milman and Yurovitsky, 1973 Boulekbache, 1981), while the activity of cytochrome oxidase increases (Ozemyuk, 1993). The increased energy metabolism corresponds to a considerable extent with motor activity (Reznichenko, 1980). In the yolk sac, the activity of proteinase, which supplies nitrogenous materials to the embryo, increases, as does the rate of amino acid incorporation into the body proteins. 

Among the most important reactions in biochemistry are those that involve substitution at phosphorus in phosphates. These reactions are involved in energy transduction, replication, transcription and recombination of nucleic acids, metabolic regulation, and metabolic pathways including biosyntheses of nucleotides, amino acids, proteins, complex lipids and complex carbohydrates. They are among the most intensively studied proteins in biochemistry, both because of their fundamental importance and because they present special challenges as research subjects. 

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