Catabolism of Nucleotides

Conversion of Nucleoside Monophosphates to Triphosphates Goes through Diphosphates Inhibitors of Nucleotide Synthesis Catabolism of Nucleotides... 

Although purine nucleosides are intermediates in the catabolism of nucleotides and nucleic acids in higher animals and humans, these nucleosides do not accumulate and are normally present in blood and tissues only in trace amounts. Nevertheless, cells of many vertebrate tissues contain kinases capable of converting purine nucleosides to nucleotides. Typical of these is adenosine kinase, which catalyzes the reaction... 

The catabolism of nucleotides is generally more complex than that of amino acids, carbohydrates, or fatty acids because the structures of the nucleotides themselves are more complex. As a result, we ll treat the subject lightly and... 

In addition to the enzymes that catalyse the formation of nucleotides and polynucleotides, a large number of catabolic systems exist which operate at all levels of the internucleotide pathways. The ribonucleases and deoxyribonucleases that degrade polynucleotides are probably not significantly involved in purine analogue metabolism, but the enzymes which dephosphorylate nucleoside 5 -monophosphates are known to attack analogue nucleotides and may be of some importance to their in vivo activity. Phosphatases of low specificity are abundant in many tissues [38], particularly the intestine [29]. Purified mammalian 5-nucleotidases hydrolyse only the nucleoside 5 monophosphates [28] and... 

Several possible mechanisms of resistance to 5-fluo-rouracU have been identified, including increased synthesis of the target enzyme, altered affinity of thymidy-late synthetase for FdUMP, depletion of enzymes (especially uridine kinase) that activate 5-fluorouracil to nucleotides, an increase in the pool of the normal metabolite deoxyuridylic acid (dUMP), and an increase in the rate of catabolism of 5-fluorouracil. 

Allopurinol markedly reduces xanthine oxide catabolism of the purine analogs, potentially increasing active 6-thioguanine nucleotides that may lead to severe leukopenia. The dose of 6-MP or azathioprine should be reduced by at least half in patients taking allopurinol. 

FIGURE 22-45 Catabolism of purine nucleotides. Note that primates as uric acid from purine degradation. Similarly, fish excrete much more... 

Figure 25-18 Pathways of catabolism of purine nucleotides, nucleosides, and free bases. Spiders excrete xanthine while mammals and birds excrete uric acid. Spiders and birds convert all of their excess nitrogen via the de novo pathway of Fig. 25-15 into purines. Many animals excrete allantoin, urea, or NH4+. Some legumes utilize the pathway marked by green arrows in their nitrogen transport via ureides.

Allantoin is the excretory product in most mammals other than primates. Most fish hydrolyze allantoin to allantoic acid, and some excrete that compound as an end product. However, most continue the hydrolysis to form urea and glyoxylate using peroxisomal enzymes.336 In some invertebrates the urea may be hydrolyzed further to ammonia. In organisms that hydrolyze uric acid to urea or ammonia, this pathway is used only for degradation of purines from nucleotides. Excess nitrogen from catabolism of amino acids either is excreted directly as ammonia or is converted to urea by the urea cycle (Fig. 24-10). 

Nucleotides - [AMINO AC IDS - L-MONOSODIUM GLUTAMATE (MSG)] (Vol 2) -as antibiotics [ANTIBIOTICS - NUCLEOSIDES AND NUCLEOTIDES] (Vol 3) -catabolism of [MINERALNUTRIENTS] (Vol 16) -electrodes for [BIOPOLYMERS - ANALYTICAL TECHNIQUES] (Vol 4) -phosphorus nmr [MAGNETIC SPIN RESONANCE] (Vol 15) -as radioactive tracers [RADIOACTIVETRACERS] (Vol 20)... 

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

The free nucleotides, nucleosides, and bases which are present in physiological fluids result from the catabolism of nucleic acids, enzyme-catalyzed degradation of bodily tissues, anabolic pathways such as the de novo or salvage pathways, or dietary intake. 

Minic Z, Pastra-Landis S, Gaill F, Herve G. Catabolism of pyrim- 65. idine nucleotides in the deep-sea tube worm Riftia pachyptila. 

An increase in uric add values up to an acute gout attack can only be attributed to a minor extent to diminished uric acid excretion from the kidneys, since decreased uricosuria due to hyprerlactacid-aemia is generally not observed unless the lactate value is >2 mmol. Excessive production of uric acid caused by increased catabolism of preformed purine nucleotides is considered to be an essential cause. This is also supported by the observation that the purine nucleotide content in hver cells is diminished after prolonged alcohol consumption. (36) (s. tab. 28.2)... 

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, ]. 

Dietary purines are largely catabolized in the gut, rather than used by the body for the synthesis of nucleic acids. The end-product of purine catabolism in humans is uric add. The diet accounts f[ir less than half of the uric add appearing in the bloodstream, Most of the plasma uric add, or urate, originates from catabolism of the purines synthesized by the body (endogenous purines). The major purines are adenine and guanine. They occur mainly as nucleotides, such as adenosine triphosphate (ATP) and guanosine triphosphate (GTP), and as parts of nucleic acids. For example, the adenine in (UvfA occurs as adenosine monophosphate, and the adenine in DNA occurs as deoxyadenosine monophosphate. 

Livers from zinc-deficient rats incorporated less phosphorus-32 into the nucleotides of RNA than livers from pair-fed controls, and DNA-dependent RNA polymerase has been shown to be a zinc-dependent enzyme (96,97). The activity of RNase is increased in zinc deficient tissues (98). This suggests that the catabolism of RNA can be regulated by zinc. 

Uric acid is the major product of catabolism of purine nucleosides adenosine and guanosine. Hypoxanthine and xanthine are intermediates along this pathway (Fig. 2). Under normal conditions, they reflect the balance between the synthesis and breakdown of nucleotides. Levels of these compounds change in various situations (e.g., they decrease in experimental tumors) when synthesis prevails over catabolism, and are enhanced during oxidative stress and hypoxia. Uric acid serves as a marker for tubular... 

Catabolism of the nucleotides (Figure 24-3, B) begins with removal of their ribose-linked phosphate, a process catalyzed by purine 5 -nucleotidase. Removal of the ribose moiety of inosine and guanosine by the action of purine-nucleoside phosphorylase forms hypoxanthine and guanine, both of which are converted to xanthme. Xanthine is converted to uric acid through the action of xanthine oxidase. 

Nucleotides are synthesized by two types of metabolic pathways de novo synthesis and salvage pathways. The former refers to synthesis of purines and pyrimidines from precursor molecules the latter refers to the conversion of preformed purines and pyrimidines—derived from dietary sources, the surrounding medium, or nucleotide catabolism—to nucleotides, usually by addition of ribose-5-phosphate to the base. De novo synthesis of purines is based on the metabolism of one-carbon compounds. 

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