Metabolism of purines

Self WT, TC Stadman (2000) Selenium-dependent metabolism of purines a selenium-dependent purine hydroxylase and xanthine dehydrogenase were purified from Clostridium purinolyticum and characterized. Proc Natl Acad Sci USA 97 7208-7213. 

Xanthine oxidoreductase (XOR) is a molybdenum-containing complex homodimeric 300-kDa cytosolic enzyme. Each subunit contains a molybdopterin cofactor, two nonidentical iron-sulfur centers, and FAD (89). The enzyme has an important physiologic role in the oxidative metabolism of purines, e.g., it catalyzes the sequence of reactions that convert hypoxanthine to xanthine then to uric acid (Fig. 4.36). 

Singhal D, Ho NF and Anderson BD (1998) Absorption and Intestinal Metabolism of Purine Dideoxynucleosides and an Adenosine Deaminase-Activated Prodrug of 2/,3/-Dideoxyinosine in the Mesenteric Vein Cannulated Rat Ileum. J Pharm Sci 87 pp 569-577. 

The pyrimidine nucleotides (predominantly UMP, CMP, and dTMP) are hydrolysed to their respective bases (uracil, cytosine, and thymine) by reactions similar to those for metabolism of purine nucleotides. The pathways of... 

Figure 2.1. Cellular metabolism of purine nucleotides. The meaning of the numbers over the arrows is explained on the next page. 

A. Probenecid blocks active reabsorption of uric acid in the proximal tubules following glomerular filtration. It does not inhibit uric acid synthesis (B), stimulate tubular secretion (C), or inhibit the metabolism of purines (D). 

Gout results from hyperuricemia i.e. increased serum uric acid levels. Normal serum uric acid level is 1-5 mg/dl. Uric acid is formed in the metabolism of purine. When the blood levels of uric acid are high, it precipitates in joints, cartilage, kidney and subcutaneous tissues and leads to various signs and symptoms. Hyperuricemia is also seen in various leukemias, lymphomas... 

The fifth chapter, Tetrahydrobiopterin and Related Biologically Important Pterins by Shizuaki Murata, Hiroshi Ichinose and Fumi Urano, describes a modern aspect of pteridine chemistry and biochemistry. Pteridine derivatives play a very important role in the biosynthesis of amino acids, nucleic acids, neurotransmitters and nitrogenmonooxides, and metabolism of purine and aromatic amino acids. Some pteridines are used in chemotherapy and for the diagnosis of various diseases. From these points of view, this article will attract considerable attention from medicinal and pharmaceutical chemists, and also heterocyclic chemists and biochemists. 

A variation of the use of standards is the method in which predetermined quantities of a standard radioactive compound are added to the solution. The fractions are collected, and, by plotting the counts of the fractions, the peak of interest can be identified. This method is especially useful in following cell metabolism of purine and pyrimidine analogs. A plot of the nucleotides in a cell extract of schistosomes containing 14C-labeled adenine and guanine nucleotides is shown in Figure 7.3.5... 

AMINOSALICYLATES AZATHIOPRINE t blood levels of azathioprine and t risk of side-effects Due to inhibition of metabolism of purines by these aminosalicylates. Monitor FBC closely... 

Figure 24-3 Metabolism of purines A, synthesis B, catabolism and C, salvage pathways.

P5. Plentl, A. A., and Schoenheimer, R., Studies in metabolism of purines and pyrimidines by means of isotopic nitrogen. J. Biol. Chem. 163, 203-217 (1944). 

Uric acid is the end product of purine metabolism in man. Consequently, abnormal levels of uric acid serve to indicate disorders of metabolism of purines or nucleic acids. Serum levels of uric acid range from 200 to 420 pmol/L In males 15 to 20% and 3 to 4% of females suffer from hyperuricaemia. 

Allopurinol reduces the amount of uric acid in blood and urine by slowing the rate at which the liver produces uric acid. It does this by inhibiting an enzyme, xanthine oxidase. This enzyme normally catalyses the later stages of metabolism of purines to uric acid. As a result of xanthine oxidase inhibition less uric acid is produced. Intermediate metabolites xanthine and hypoxanthine are produced in larger amounts, but these are freely water soluble and eliminated by the kidneys. 

---