Purine biosynthesis catabolism

Another form of detoxified ammonia that is used in nitrogen excretion is uric acid. Uric acid is the predominant nitrogen excretory product in birds and terrestrial reptiles (turtles excrete urea, whereas alligators excrete ammonia unless they are dehydrated, in which case they, too, excrete uric acid). Uric acid formed as a product of amino acid catabolism involves the de novo pathway of purine biosynthesis therefore, its formation from NH3 liberated in amino acid catabolism is described elsewhere (see chapter 23). In mammals, uric acid is exclusively an intermediate in purine... 

Ashihara H, Sano H, Crozier A. Caffeine and lelaled purine alkaloids biosynthesis, catabolism, function and gmetic engineering. Phytochemistry 2008 69(4) 841-56. 

An increased production of uric acid can result from clinical conditions in which there is a rapid increase in the rate of degradation of purine nucleotides. This degradation occurs as a result of the turnover or breakdown of nucleic acids and soluble nucleotides in the cell often associated with breakdown of the cell itself. Examples of this would include the acute leukemias and hemolytic anemias (2). In addition, the degradation of purine nucleotides can occur as a result of alterations in the energy of the cell which enhance the breakdown of ATP. Examples of this might include starvation, muscular exertion, and hypoxia. In some of these latter conditions related to the catabolism of purine nucleoside triphosphates, there may also be compensatory increase in the rate or purine biosynthesis de novo related to the release of feedback inhibition at the level of PRPP synthetase and/or PRPP amidotransferase. 

The main source of C, units is the hydroxymethyl group of serine, which is transferred to THF by serine hydroxymethyltransferase (EC 2.1.2.1), forming fV -hydroxymethyl-THF (activated form dehyde). Production of C, units during histidine catabolism and in the anaerobic degradation of purines is of particular importance. C, units are incorporated during purine biosynthesis, and they provide the S-methyl group of thymine. C units are interconverted while attached to THF (Hg.2). For other metabolic sources and uses of C units, see legend to Fig.2. 

The fructose-induced increase in uric acid synthesis observed can potentially occur either by 1) increased purine biosynthesis de novo or 2) increased nucleotide catabolism. We have shown that fructose can stimulate PP-ribose-P production in human erythrocytes incubated in vitro. Since increased intracellular PP-ribose-P... 

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]. 

In summary, the biochemical function of folate coenzymes is to transfer and use these one-carbon units in a variety of essential reactions (Figure 2), including de novo purine biosynthesis (formylation of glycinamide ribonucleotide and 5-amino-4-imidazole carboxamide ribonucleotide), pyrimidine nucleotide biosynthesis (methylation of deoxyuridylic acid to thy-midylic acid), amino-acid interconversions (the interconversion of serine to glycine, catabolism of histidine to glutamic acid, and conversion of homocysteine to methionine (which also requires vitamin B12)), and the generation and use of formate. 

The biosynthesis of purines and pyrimidines is stringently regulated and coordinated by feedback mechanisms that ensure their production in quantities and at times appropriate to varying physiologic demand. Genetic diseases of purine metabolism include gout, Lesch-Nyhan syndrome, adenosine deaminase deficiency, and purine nucleoside phosphorylase deficiency. By contrast, apart from the orotic acidurias, there are few clinically significant disorders of pyrimidine catabolism. 

Polysaccharides, 44, 58 Prokaryote Cell, 7 Proline, 439 Promoters, 391 Protamines, 149 Proteans, 151 Protein Biosynthesis, 448 Protein Catabolism, 428 Protein Maturation, 449 Proteins, 262 Purine Metabolism, 379 Purines, 113 Pyridoxine, 229 Pyrimidines, 113 Pyruvate Kinase, 288... 

Proteins are hydrolysed in the stomach by pepsin to form amino acids. Further hydrolysis occurs in the intestine. The amino acids are absorbed. Any amino acids in excess of those needed to replace the wear and tear of tissues, and for biosynthesis to hormones, pyrimidines, purines, etc., are used for gluconeogenesis, or for energy metabolism. However, catabolism of amino acids generates ammonium ions (NH4+), which are very toxic. Accordingly, NH/ is disposed of by conversion to urea which is non-toxic and is readily excreted via the kidney. 

Information on cellular metabolic organization of caffeine biosynthesis and catabolism links to purine nucleotide metabolism, intercellular translocation, and accumulation mechanisms at specific cellular sites, such as chloroplasts and vacuoles, have yet to be fully revealed. Cell-, tissue-, and organ-specific synthesis and possibly catabolism of purine alkaloids may be regulated by unique and unknown developmental- and environmental-specific control mechanisms. A great deal of fascinating purine alkaloid biology in plants still remained to be discovered. 

Little is known about the physiological significance of caffeine formation or the role of caffeine in plants. Perhaps some of these answers will be forthcoming during the next few decades as researchers begin to probe into the metabolism (biosynthesis and catabolism) of caffeine and relate it to purine nucleotide, nucleic acid, and other types of metabolism in coffee plants. 

Nucleotide biosynthesis, like nucleotide catabolism, is relatively complex. Thus, we ll again look at only one example, adenosine monophosphate. Purine nucleotides are formed by initial attachment of an -NH2 group to ribose, followed by multistep buildup of the heterocyclic base. The attachment of -NH2 takes place by a nucleophilic suhstitution reaction of ammonia with 5-phosphoribosyl a-diphosphate to give /3-5-phosphorihosylamine and probably involves an SNl-like loss of diphosphate ion with formation of an 0x0-nium-ion intermediate. Although we ll not cover the details of its formation, inosine monophosphate (IMP) is the first fully formed purine ribonucleotide, with adenosine monophosphate (AMP) derived fi-om it. 

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