Purines uric acids

Purine, uric acid, and other associated compounds play a role in organic synthesis of industrial products. 

Another purine, uric acid, occurs widely in nature—it is used by birds, and to some extent by humans, as a way to excrete excess nitrogen—but it causes much distress in humans when crystalline uric acid is deposited in joints. We call the pain gout and itisn tfunny. The solution is a specific inhibitor of the enzyme producing uric acid and it is no surprise that a compound closely resembling uric acid, allopurinol, is the best. 

B. The DNA Funhouse. There is excess uric acid due to shunting through the HMP (Penthouse Powerhouse) shunt to form purines. Uric acid stones may deposit in the urinary tract. 

Fischer, Emil (1852-1919). Basic research on sugars, purines, uric acid, enzymes, nitric acid, ammonia. Pioneer work in stereochemistry. Nobel Prize 1902. 

Figure 6 is a metabolic map of nucleoprotein catabolism, and Table 6 shows some of the components that can be recovered from scrapings of normal skin, from callus, and from psoriatic scales. In conjunction with the preceding it shows that about 5% of the RNA and less than 1% of the DNA is left in the normal horny layer while up to one-third of the RNA and DNA is still present in the cells of the parakeratotic horny layer of psoriasis. Xanthine and hypoxanthine can be found in psoriatic scales and presumably result from catabolism of nucleic acid purines. Uric acid, although present in the scales, probably comes from the blood, since xanthine oxidase has not been found in human epidermis (B15, B17). Pyrimidine breakdown products have not been found. This might... 

In humans, uric acid is the end product of the degradation of purines. Uric acid serves no known physiologic purpose and therefore is regarded as a waste product. In lower animals, the enzyme uricase breaks down uric acid to the more soluble allantoin, and thus uric acid does not accumulate. Gout occurs exclusively in humans in whom a miscible pool of uric acid exists. Under normal conditions, the amount of accumulated uric acid is about 1200 mg in men and about 600 mg in women. The size of the urate pool is increased severalfold in individuals with gout. This excess accumulation may result from either overproduction or underexcretion. 

Another purine, uric acid, occurs wideiy in nature—it is used by birds, and to some extent by humans, as a j way to excrete excess nitrogen—but... 

Lesch-Nyhan syndrome Hypoxanthine-guanine phosphoribosyltrans-f erase Purines, uric acid Mental retardation, self-mutilation... 

Plasma and urinary purines Uric acid, xanthine and hypoxanthine in plasma and urine in Family B are also given in Table 1. The plasma and urine uric acid levels were greatly increased in NB and his mother (CB) when compared with appropriate controls. Urinary hypo-xanthine levels were excessive in both (Table 1). The urine purine creatinine ratio confirmed gross purine overproduction in both, that in the mother (CB) being approximately twice normal for a healthy adult female. Values in the father (JB) were normal for age and sex. 

Another class of natural products investigated by Fischer was the purines. Uric acid had been isolated by Scheele in 1766 and a number of other compounds in the group had been obtained before Fischer began studying caffeine in 1881. Among the other members of the group studied by Fischer were xanthine, theobromine and guanine. Fischer synthesised some of the purines and established the relationship between them. 

Much of the early chemistry highlighted the relationships among urea, allantoic acid, aUentoin, and the fully elaborated purines, uric acid, caffeine, theobromine, theophylline, and xanthine (Figure 13.7). 

Pigeon liver has been used as the system of choice in studying purine biosynthesis, originally because birds were known to excrete large amounts of purine (uric acid), and later because of the knowledge gained with this favorable system. It was found that the first purine compound to accumulate is inosinic acid. Studies with labeled precursors showed that the purine skeleton of this compound was built from the units shown in (I). ... 

Purine Mast breads and cereals. Wheat germ. purines (uric-acid forming sub-... 

Uric acid C5H4N4O3 Purines Dissolves on gentle warming and is reprecipitated unchanged on dilution. The solution in cone. H2SO4 darkens on heating. 

This enzyme, sometimes also called the Schardinger enzyme, occurs in milk. It is capable of " oxidising" acetaldehyde to acetic acid, and also the purine bases xanthine and hypoxanthine to uric acid. The former reaction is not a simple direct oxidation and is assumed to take place as follows. The enzyme activates the hydrated form of the aldehyde so that it readily parts w ith two hydrogen atoms in the presence of a suitable hydrogen acceptor such as methylene-blue the latter being reduced to the colourless leuco-compound. The oxidation of certain substrates will not take place in the absence of such a hydrogen acceptor. 

Birds excrete nitrogen as uric acid Uric acid is a purine having the molecular formula C5H4N4O3 it has no C—H bonds Write a structural formula for uric acid... 

Deficiency or Toxicity in Humans. Molybdenum deficiency in humans results in deranged metaboHsm of sulfur and purines and symptoms of mental disturbances (130). Toxic levels produce elevated uric acid in blood, gout, anemia, and growth depression. Faulty utiH2ation results in sulfite oxidase deficiency, a lethal inborn error. 

The presence of nucleic acids ia yeast is oae of the maia problems with their use ia human foods. Other animals metabolize uric acid to aHantoia, which is excreted ia the uriae. Purines iagested by humans and some other primates are metabolized to uric acid, which may precipitate out ia tissue to cause gout (37). The daily human diet should contain no more than about 2 g of nucleic acid, which limits yeast iatake to a maximum of 20 g. Thus, the use of higher concentrations of yeast proteia ia human food requires removal of the nucleic acids. Unfortunately, yields of proteia from extracts treated as described are low, and the cost of the proteia may more than double. 

Adenine (6-amino purine) and guanine (2-amino-6-oxy purine), the two common purines, are found in both DNA and RNA (Figure 11.4). Other naturally occurring purine derivatives include hypoxanthlne, xanthine, and uric acid (Figure 11.5). Flypoxanthine and xanthine are found only rarely as constituents of nucleic acids. Uric acid, the most oxidized state for a purine derivative, is never found in nucleic acids. 

FIGURE 11.5 Other naturally occurring purine derivatives—hypoxanthine, xanthine, and uric acid. 

The presence of uricase assists the uric acid to be hydrolysed, and the end product of purine degradation is completed with the addition of uricase. 

Anti-gout Drugs. Figure 1 Xanthine oxidase-catalyzed reactions. Xanthine oxidase converts hypoxanthine to xanthine and xanthine to uric acid, respectively. Hypoxanthine and xanthine are more soluble than uric acid. Xanthine oxidase also converts the uricostatic drug allopurinol to alloxanthine. Allopurinol and hypoxanthine are isomers that differ from each other in the substitution of positions 7 and 8 of the purine ring system. Although allopurinol is converted to alloxanthine by xanthine oxidase, allopurinol is also a xanthine oxidase inhibitor. Specifically, at low concentrations, allopurinol acts as a competitive inhibitor, and at high concentrations it acts as a noncompetitive inhibitor. Alloxanthine is a noncompetitive xanthine oxidase inhibitor. XOD xanthine oxidase. 

Uric acid is the endproduct of purine metabolism in man. Uric acid has a lower solubility than its progenitor metabolites, hypoxanthine and xanthine. Impaired uric acid elimination and/or increased uric acid production result in hyperuricemia and increase the risk of gouty arthritis. At physiological pH, 99% of the uric acid molecules are actually in the form of the urate salt. A decrease in pH increases the fraction of uric acid molecules relative to urate molecules. Uric acid possesses lower solubility than urate. 

Xanthine oxidase (XOD) is the key enzyme in purine catabolism. XOD catalyses the conversion ofhypoxan-thine to xanthine and of xanthine to uric acid, respectively. The uricostatic drug allopurinol and its major metabolite alloxanthine (oxypurinol) inhibit xanthine oxidase. 

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