Adenylate catabolism

Although adenylic acid deaminase is a well-known enzyme that has been isolated in crystalline form, little work has been reported on its substrate specificity evidence for the deamination of 4-aminopyrazolo[3,4-d]pyrimidine ribonucleotide has been presented [118], but it is not known if it catabolizes any of the other intracellularly formed adenylic acid analogues. 

The breakdown of fatty acids in (3-oxidation (see Topic K2) is controlled mainly by the concentration of free fatty acids in the blood, which is, in turn, controlled by the hydrolysis rate of triacylglycerols in adipose tissue by hormone-sensitive triacylglycerol lipase. This enzyme is regulated by phosphorylation and dephosphorylation (Fig. 5) in response to hormonally controlled levels of the intracellular second messenger cAMP (see Topic E5). The catabolic hormones glucagon, epinephrine and norepinephrine bind to receptor proteins on the cell surface and increase the levels of cAMP in adipose cells through activation of adenylate cyclase (see Topic E5). The cAMP allosterically activates... 

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. 

A major function of the Bcl-2 family members is to regulate cytochrome c release via their interaction with the outer mitochondrial membrane. As described above, cytochrome c release is an important first step in initiating apoptotic events in cells because of its ability to interact with and thereby activate Apaf-1. However, mitochondria can also release a number of other proteins during apoptosis, such as AIF, certain procaspases, catabolic enzymes, adenylate kinase 2 and SMAC/Diablo. The role of these proteins in the apoptotic process is not known with certainty. Anti-apoptotic proteins of the Bcl-2 family possess membrane anchoring domains at their carboxy terminus that target the... 

Guanylate reductase, which deaminates this nucleotide, catalyzes a reductive, rather than hydrolytic, deamination and has been discussed in Chapter 9. Like adenylate deaminase, it has a catabolic role and also functions in purine nucleotide interconversion. A guanosine deaminase has recently been identified in a pseudomonad (13), but it is not known to occur in animal cells. 

Studies by Burger and Lowenstein (29) illustrate some of the complexities of these alternative pathways of nucleotide catabolism and their control. Pathways of deamination and dephosphorylation of adenylate... 

The report that cAMP relieves glucose repression of iV-acetylkanamycin amidohydrolase in Streptomyces kanamyceticus, a prokaryote ( ), indicates that the repression mechanism resembles that of different catabolic enzymes in bacteria, which proceed via the inhibition of adenylate cyclase, the enzyme that converts ATP to cAMP (D 10.4). As a consequence the concentration of cAMP decreases and the transcription by RNA polymerase of operons subjected to cAMP control is inhibited (catabolite repression). In eucaryotes, however, catabolite repression could not be demonstrated. In Penicillium cyclopium for instance, glucose suppression of benzodiazepine alkaloid biosynthesis cannot be overcome by administration of cAMP or cAMP derivatives. 

The low RBC ATP concentration is the most probable explanation for the hemolysis (1). In vitro studies of adenosine metabolism by intact patient s RBC showed as expected, a markedly decreased ATP synthesis from adenosine moreover, metabolic studies of adenylic nucleotides labelled with radioactive adenine indicate that AMP degradation (probably by hydrolysis of the phosphate ester followed by deamination of adenosine) is abnormally elevated in the patient s erythrocytes. Thus, the low RBC ATP concentration appears to be secondary to both a diminished synthesis of AMP from adenosine and an excessive catabolism of AMP. 

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]. 

Coon and co-workers ttt-ltJia) discovered and crystallized an enzyme Itia) named hydroxylamine kinase that degrades ATP in the presence of bicarbonate and hydroxylamine. It was believed that adenylic acid and pyrophosphate were products of this reaction and it was considered that this enzyme participated in the carboxylation reaction in leucine catabolism by activating COi. Active CO was presumed to be adenyl-COj. Later this enzyme was found not to participate in the carboxylation reactions. More recently Kupiecki and Coon lt4b) established that hydroxylamine kinase is very probably identical with pyruvic kinase and fluoro kinase of Tietz and Ochoa (96). Interesting differences were found in the activation of the different enzyme functions by metal ions. Zn, but not Mg++, promoted hydroxylamine kinase activity, whereas Mg, but not Zn promoted iluorokinase and pyruvic kinase activity. 

In the second experiment, the rapid degradation of AMP by pigeon liver was mediated almost entirely by phosphatase action rather than by deamination (67). Since the specific activity of IMP formed from small precursors in incubated homogenates was unaffected by the simultaneous breakdown of adenylic acid, it was concluded that adenosine, rather than IMP, was the first product of AMP catabolism. If IMP were formed from AMP the specific activity of IMP would have been lowered. 

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