Adenine synthesis from uric acid

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... 

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. 

Most of the free purines derived from the breakdown of DNA, RNA, and nucleotides in the diet are catabolized to xanthine and then to uric acid in the gut mucosa. The AMP and GMP biosynthesized in the body can also be bmken down to free purines, such as adenine, guanine, and hypoxanthine. These purines, in contrast to those derived frcim the diet, are largely reused for the synthesis of ATP and GTP- They are first converted back to AMP or GMP in a pathway of reutiliza-lion called the purine salvage pathway. For example, adenine phosphoribosyl-transferase (PRPP) catalyzes the conversion of adenine to AMP. Here, PRPP serves as the source of the phosphoribose group. Pyrophosphate is a product of the reaction. 

Alcoholism affects about 10% of the drinking population and alcohol (ethanol) abuse has been implicated in at least 20% of admissions to general hospitals. This chronic disease exhibits high mortality due to a wide variety of factors. Ethanol produces effects in virtually every organ system. The biochemical effects of ethanol are due to increased production of NADH that decreases the [NAD ]/[NADH] ratio in the cytoplasm of liver cells at least tenfold from the normal value of about 1000. Increased production of lactate and inhibition of gluconeo-genesis (Chapter 15) result. The hyperuricemia associated with ethanol consumption has been attributed to accelerated turnover of adenine nucleotides and their catabolism to uric acid (Chapter 27). Alcohol increases hepatic fatty acid and triacylglycerol synthesis and mobilization of fat from adipose tissue, which can lead to fatty liver, hepatitis, and cirrhosis. These effects are complicated by a deficiency of B vitamins and protein. 

The few deficient patients examined thus far have shown, not the expected accumulation of AMP in exercised muscles, but rather a depletion of all adenine nucleotides and their loss from muscle as nucleosldes >. This suggests a compensatory dephosphorylation by nucleotidase when AMP deaminase is absent, in order to lower AMP levels. Since it is now known that muscle is a major site of de novo purine synthesis, exercise in affected patients might accelerate both purine synthesis and breakdown, and predispose them toward hyperuricemia and gout. It may be more than coincidental, therefore, that 1 of our patients has gout, 2 others have had elevated uric acid levels, and another case of the deficiency coexisting with gout has been reported. The evidence at present is too meager to justify other than a cautionary attitude. 

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