Purine nucleotide catabolism

This enzyme returns the major products of purine nucleotide catabolism to nucleotide forms. 

Adenine phosphoribosyltransferase catalyzes the conversion of adenine to AMP in many tissues, by a reaction similar to that of hypoxanthine-guanine phosphoribosyltransferase, but is quite distinct from the latter. It plays a minor role in purine salvage since adenine is not a significant product of purine nucleotide catabolism (see below). The function of this enzyme seems to be to scavenge small amounts of adenine that are produced during intestinal digestion of nucleic acids or in the metabolism of 5 -deoxy-5 -methylthioadenosine, a product of polyamine synthesis. 

Degradation of pyrimidine bases. Parts of this pathway are widely distributed in nature. The entire pathway is found in mammalian liver. As in purine nucleotide catabolism, no ATP results from catabolism, and the ribose-1-phosphate is released during catabolism before destruction of the base. 

Purine nucleotide catabolism is outlined in Figure 15.12. There is some variation in the specific pathways used by different organisms or tissues to degrade AMP. In muscle, for example, AMP is initially converted to IMP by AMP deaminase (also referred to as adenylate aminohydrolase). IMP is subsequently hydrolyzed to inosine by 5 -nucleotidase. In most tissues, however, AMP is hydrolyzed by 5 -nucleotidase to form adenosine. Adenosine is then deaminated by adenosine deaminase (also called adenosine aminohydrolase) to form inosine. 

Although the mechanism of fructose-induced purine nucleotide catabolism has been well studied in liver cells (8,9), this is not the case for glycerol-induced catabolism. In the present work, we have characterized the adenine nucleotide catabolism induced by glycerol in isolated rat liver cells and have compared it with that induced by fructose. We have also studied the effects of glycerol and fructose on purine synthesis novo and on phospho-ribosylpyrophosphate (PP-ribose-P) availability in these cells. 

Acetate is a final product of ethanol oxidation. Its utilization by muscles and brain cells requires its conversion to acetyl-CoA by acetyl-CoA synthase. This consumes ATP, yielding AMP and energy deficits, which in turn stimulate purine nucleotide catabolism and hyperuricemia (Lavoie and Butterworth 1995). Through such mechanisms, alcohol may exert direct toxic elfects uncovering pre-existing subclinical TD-dependent energy shortages. 

Bios5mthetic pathways of naturally occurring cytokinins are illustrated in Fig. 29.5. The first step of cytokinin biosynthesis is the formation of A -(A -isopentenyl) adenine nucleotides catalyzed by adenylate isopentenyltransferase (EC 2.5.1.27). In higher plants, A -(A -isopentenyl)adenine riboside 5 -triphosphate or A -(A -isopentenyl)adenine riboside 5 -diphosphate are formed preferentially. In Arabidopsis, A -(A -isopentenyl)adenine nucleotides are converted into fraws-zeatin nucleotides by cytochrome P450 monooxygenases. Bioactive cytokinins are base forms. Cytokinin nucleotides are converted to nucleobases by 5 -nucleotidase and nucleosidase as shown in the conventional purine nucleotide catabolism pathway. However, a novel enzyme, cytokinin nucleoside 5 -monophosphate phosphoribo-hydrolase, named LOG, has recently been identified. Therefore, it is likely that at least two pathways convert inactive nucleotide forms of cytokinin to the active freebase forms that occur in plants [27, 42]. The reverse reactions, the conversion of the active to inactive structures, seem to be catalyzed by adenine phosphoiibosyl-transferase [43] and/or adenosine kinase [44]. In addition, biosynthesis of c/s-zeatin from tRNAs in plants has been demonstrated using Arabidopsis mutants with defective tRNA isopentenyltransferases [45]. 

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