Nucleotide functions energy metabolism

Figure 9.8 outlines how matrix vesicles increase and decrease the concentration of pyrophosphate. NTP-PPi hydrolase synthesizes pyrophosphate from stromal fluid nucleotides, mostly ATP (ATP —> AMP + PPi). Many cells secrete ATP into the extracellular fluid and it passes into the blood plasma where it affects a variety of cells independently of its function in intracellular energy metabolism. In mice, a nonfunctional ANK protein or a deletion of NTP-PPi hydrolase decreases the extracellular pyrophosphate concentration and the phenotype exhibits extensive mineralization. Thus, the hydrolysis of pyrophosphate appears to be a major function of alkaline phosphatase (TNAP) after the calcium phosphate precipitate has raptured the matrix vesicles. Rapid mineralization of collagen and the rest of the osteoid matrix ensue without a need to transport any more Ca2+ or Pi to the region. 

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... 

This discussion will be limited to aerobic hydroxylation reactions. As already mentioned, it is a reaction which appears to be restricted to the metabolism of rather inert molecules. The reason for this is not apparent, but it may be because the reaction is energetically expensive for the cell. If, in the hydration type of hydroxylation reaction, a pyridine nucleotide functions as the hydrogen acceptor, the subsequent reoxidation of the DPNH or TPNH over the flavin-cytochrome hydrogen transport system could be coupled to the synthesis of 3 moles of ATP per mole of DPNH oxidized. In the aerobic type of hydroxylation reaction, utilizing TPNH as the electron donor, the oxidation of the TPNH is apparently not coupled to high-energy phosphate-bond synthesis and the cell therefore loses the equivalent of three ATP s. 

The so-called salvage pathways are available in many cells to scavenge free purine and pyrimidine bases, nucleosides, and mononucleotides and to convert these to metabolically useful di- and trinucleotides. The function of these pathways is to avoid the costly (energy) and lengthy de novo purine and pyrimidine biosynthetic processes. In some cells, in fact, the salvage pathways yield a greater quantity of nucleotides than the de novo pathways. The substrates for salvage reactions may come from dietary sources or from normal nucleic acid turnover processes. 

Analysis of regulatory networks involved in the adaptation of the metabolism of microorganisms to various environmental conditions, such as starvation, revealed the particular importance of nucleotides and amino acids. These compounds function as signals for starvation, precursors in metabolic pathways, energy sources or are involved in enz3une activity regulation [10,32,33,42,44,110-112]. They are usually determined off -line by HPLC [8,10,32,33,42,44,112], as chromatographic or electrophoretic determinations allow the simultaneous determination of all compounds of... 

Uric acid that is produced in man is essentially the product of the action of the enzyme xanthine oxidase on xanthine and hypoxanthine. A tiny amount of uric acid may be ingested as part of the diet, but the great bulk is the result of the action of this enzyme on these two purines. These purines are themselves produced either as a result of the breakdown of cellular material in toto, the turnover of nucleic acids in the cells, or as a result of the intermediary metabolism of various purine nucleotide derivatives. These latter compounds are active in the flow of energy, in methyl group transfer reactions, and as part of the functional molecule of many vitamins. There is direct and indirect evidence that some of the uric acid derives from all these sources. Essentially this evidence consists of the demonstration that other parts of the nucleie acids are found in the urine, such as pyrimidine breakdown products (P9) and methylated purines, which are found only in nucleic acids. There is also isotopic evidence that some labeled purines appear in the urine too quickly after administration of radioactive precursors... 

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