Purine catabolism, effect

For birds, insects, and reptiles, which have an egg stage during development, so that water availability is severely restricted, the synthesis of a highly soluble excretory product would have serious osmotic consequences therefore most of the ammonia is converted to the virtually insoluble uric acid (urate). This product can be safely retained in the egg or excreted as a slurry of fine crystals by the adult. In birds that nest colonially this can accumulate in massive amounts on islands off the coast of Peru cormorants have deposited so much that this guano (hence the name guanine) is collected for use as a fertiliser. Uric acid is less effective as an excretory product, since it has a lower nitrogen content than urea (33%) and is more expensive to synthesise (2.25 molecules ATP per atom of nitrogen). Mammals do produce uric acid but as a product of purine catabolism (see above). 

The absence of effect of ethanol on purine catabolism in the perfused liver of fasted rats, could be explained by the nearabsence of glycolysis in this preparation (Woods and Krebs, 1971), resulting in the disappearance of the interaction with the respiratory chain. 

The absence of effect of ethanol on purine catabolism in isolated hepatocytes from fed rats may be related to a lower rate of glycolysis (Seglen, 1974) or to its lesser inhibition by ethanol, as suggested by the limited increases in a-glycerol-P. Experiments are in progress in order to verify this hypothesis. 

Mercaptopurine (6-MP) is an oral purine analog that is converted to a ribonucleotide to inhibit purine synthesis. Mercaptopurine is converted into thiopurine nucleotides, which are catabolized by thiopurine S-methyltransferase (TPMT), which is subject to genetic polymorphisms and may cause severe myelosuppression. TPMT status may be assessed prior to therapy to reduce drug-induced morbidity and the costs of hospitalizations for neutropenic events. Mercaptopurine is poorly absorbed, with a time to peak concentration of 1 to 2 hours after an oral dose. The half-life is 21 minutes in pediatric patients and 47 minutes in adults. Mercaptopurine is used in the treatment of acute lymphocytic leukemia and chronic myelogenous leukemia. Significant side effects include myelosuppression, mild nausea, skin rash, and cholestasis. When allopurinol is used in combination with 6-MP, the dose of 6-MP must be reduced by 66% to 75% of the usual dose because allopurinol blocks the metabolism of 6-MP. 

As indicated in Fig. 25-18, free adenine released from catabolism of nucleic acids can be deaminated hydrolytically to hypoxanthine, and guanine can be deaminated to xanthine.328 The molybdenum-containing xanthine oxidase (Chapter 16) oxidizes hypoxanthine to xanthine and the latter on to uric acid. Some Clostridia convert purine or hypoxanthine to xanthine by the action of a selenium-containing purine hydroxylase.3283 Another reaction of xanthine occurring in some plants is conversion to the trimethylated derivative caffeine. 328b One of the physiological effects of caffeine in animals is inhibition of pyrimidine synthesis.329 However, the effect most sought by coffee drinkers may be an increase in blood pressure caused by occupancy of adenosine receptors by caffeine.330... 

The lung also possesses nonenzymatic antioxidants such as vitamin E, beta-carotene, vitamin C, and uric acid. Vitamin E is lipid-soluble and partitions into lipid membranes, where it is positioned optimally for maximal antioxidant effectiveness. Vitamin E converts superoxide anion, hydroxyl radical, and lipid peroxyl radicals to less reactive oxygen metabolites. Beta-carotene also accumulates in cell membranes and is a metabolic precursor to vitamin A. Furthermore, it can scavenge superoxide anion and react directly with peroxyl-free radicals, thereby serving as an additional lipid-soluble antioxidant. Vitamin C is widely available in both extracellular and intracellular spaces where it can participate in redox reactions. Vitamin C can directly scavenge superoxide and hydroxyl radical. Uric acid formed by the catabolism of purines also has antioxidant properties and primarily scavenges hydroxyl radical and peroxyl radicals from lipid peroxidation. 

The detailed mechanism of myocardial protection via PC is not fully understood yet. Many pathways have been proposed and include myocardial stunning, synthesis of heat-shock proteins, involvement of G-proteins, and nitric oxide production [3-5]. The generally accepted model is that the ischemic phase leads to enhanced catabolism of purine nucleotides, resulting in a high level of adenosine. These activate PKC and a cascade of signaling steps leading to activation of MAP, MAPK and MAPKK, culminating in a marked effect on ATP-dependent channels [3,4,6, ]. 

Tn recent years there has been an increased interest in assessing the human health effects from environmental exposure to trace metals. Studies of occupational exposures and dietary intakes of trace metals have required the refinement and development of analytical techniques for the analyses of low elemental concentrations in complex matrices. Molybdenum is one of the trace metals that has been the subject of intensive study because it is an essential trace element in both plant and animal nutrition. It is an integral constituent of several metalloenzymes including xanthine oxidase, which is the last enzyme in the catabolic pathway of purines. Extensive ingestion of molybdenum has been shown to cause molybdenosis in cattle. Many of the features of this condition can be ascribed to induced copper deficiency. Whether biochemical changes or adverse health effects in humans can be attributed to excessive exposure to molybdenum is not known. 

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. 

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