Enzyme xanthine oxidase

It is possible that dietary flavonoids participate in the regulation of cellular function independent of their antioxidant properties. Other non-antioxidant direct effects reported include inhibition of prooxidant enzymes (xanthine oxidase, NAD(P)H oxidase, lipoxygenases), induction of antioxidant enzymes (superoxide dismutase, gluthathione peroxidase, glutathione S-transferase), and inhibition of redox-sensitive transcription factors. 

Brass, C.A., Narciso, J. and GoUan, J.L. (1991). Enhanced activity of the free radical producing enzyme xanthine oxidase in hypoxic rat liver. J. Clin. Invest. 87, 424—431. 

Most patients in the United States are treated with allopurinol, which usually is effective if the dosage is titrated appropriately. The drug and its primary active metabolite, oxypurinol, reduce serum uric acid concentrations by inhibiting the enzyme xanthine oxidase, thereby blocking the oxidation of hypoxanthine and xanthine to uric acid. 

Of the mammalian enzymes, the sulphite oxidase of bovine liver has only recently been discovered to contain molybdenum (15). The better known molybdenum enzymes, xanthine oxidase from cows milk (31) and aldehyde oxidase from rabbit liver (16) are closely related to one another as they are to the xanthine dehydrogenases from chicken liver (17) and from bacteria (18). 

Of experimental methods for studying the metal in enzymes, light absorption in the visible region from molybdenum chromophores is likely to be weak and frequently masked by stronger absorption from other enzyme constituents. Indeed only recently has a small molybdenum contribution to the absorption spectrum of even the most studied of these enzymes, xanthine oxidase, been demonstrated 33, see Section V F). 

Most in vitro studies of xanthines have centered around the enzyme xanthine oxidase. Bergmann and co-workers 40-4)) have examined the main oxidative pathways in the xanthine oxidase catalyzed oxidation of purines. The mechanism proposed by these workers 41 > is that the enzyme binds a specific tautomeric form of the substrate, regardless of whether or not that form represents the major structure present in solution. It is then proposed that the purine, e.g., xanthine, undergoes hydration at the N7=C8 double bond either prior to or simultaneously with dehydrogenation of the same position. Accordingly, the process would involve either pathway a or b. Fig. 15. Route a would give a lactim form of the oxidized purine, while b would give the cor-... 

Molybdenum (Mo) is present in all plant, human, and animal tissues, and is considered an essential micronutrient for most life forms (Schroeder et al. 1970 Underwood 1971 Chappell and Peterson 1976 Chappell et al. 1979 Goyer 1986). The first indication of an essential role for molybdenum in animal nutrition came in 1953 when it was discovered that a flavoprotein enzyme, xanthine oxidase, was dependent on molybdenum for its activity (Underwood 1971). It was later determined that molybdenum is essential in the diet of lambs, chicks, and turkey poults (Underwood 1971). Molybdenum compounds are now routinely added to soils, plants, and waters to achieve various enrichment or balance effects (Friberg et al. 1975 Friberg and Lener 1986). 

Vickers, S., Schiller, H. J., Hildreth, J. E., Bulkley, G. B., Immunoaffmity localization of the enzyme xanthine oxidase on the outside surface of endothelial cell plasma membrane. Surgery 124 (1998), p. 551-560... 

The anticancer drug 6-mercaptopurine is deactivated by the enzyme xanthine oxidase. A cancer patient being treated with 6-meicaptopurine develops hyperuricemia, and the physician decides to give the patient allopurinoL... 

Gout is one of the most ancient diseases its clinical characteristics have been known for at least 2000 years. It is now very effectively treated with drugs that decrease production of uric acid by inhibition of the enzyme xanthine oxidase in purine degradation (Figure 10.9) (allopurinol), and a drug that increases the excretion of uric acid (probenecid)... 

The amino groups are replaced with oxygen. Although here a biochemical reaction, the same can be achieved under acid-catalysed hydrolytic conditions, and resembles the nucleophilic substitution on pyrimidines (see Section 11.6.1). The first-formed hydroxy derivative would then tautomerize to the carbonyl structure. In the case of guanine, the product is xanthine, whereas adenine leads to hypoxanthine. The latter compound is also converted into xanthine by an oxidizing enzyme, xanthine oxidase. This enzyme also oxidizes xanthine at C-8, giving uric acid. 

In the most important degradative pathway for adenosine monophosphate (AMP), it is the nucleotide that deaminated, and inosine monophosphate (IMP) arises. In the same way as in GMP, the purine base hypoxanthine is released from IMP. A single enzyme, xanthine oxidase [3], then both converts hypoxanthine into xanthine and xanthine into uric acid. An 0X0 group is introduced into the substrate in each of these reaction steps. The oxo group is derived from molecular oxygen another reaction product is hydrogen peroxide (H2O2), which is toxic and has to be removed by peroxidases. 

It inhibits the terminal steps in uric acid biosynthesis by inhibiting enzyme xanthine oxidase. During therapy with allopu-rinol the uric acid plasma levels decline. 

The bioavailability of azathioprine (80%) is superior to 6-MP (50%). After absorption azathioprine is rapidly converted by a nonenzymatic process to 6-MP. 6-Mercaptopurine subsequently undergoes a complex biotransformation via competing catabolic enzymes (xanthine oxidase and thiopurine methyltransferase) that produce inactive metabolites and anabolic pathways that produce active thioguanine nucleotides. Azathioprine and 6-MP have a serum half-life of less than 2 hours however, the... 

The inhibition of enzyme systems dues nut necessarily cause unwarned effects. Consider the enzyme xanthine oxidase. It contains two atoms of molybdenum, four Fe2S2, and two FAD (flavin adenine dinucleotidei moieties, and it has a molecular weight of 275.000-300.000. There is no evidence that the two units (Mo/SFe Sj/FAD) are near each other or interact in any way. It is believed that the immediate environment of each molybdenum atom consists of one oxygen and three sulfur atoms (additional ligands may be present) 12... 

Two of the carbonyl groups have gone and the imidazole ring has been replaced by a pyrazoie ring. Purines from DNA are degraded in the body to xanthine, which is oxidized to uric acid. Allopurinol binds to the enzyme xanthine oxidase but inactivates it by not reacting. In fact it imitates not uric acid but the true substrate xanthine in a competitive fashion. This enzyme plays a minor part in human metabolism so inhibiting it is not serious—it just prevents overproduction of uric acid. 

The rabbit heart contains only trace amounts of the enzyme xanthine oxidase (as does the human heart) [37,38]. Therefore, this enzyme probably does... 

Xanthine dehydrogenase The enz)une is used in the catabolism of the purine ring. It catalyzes the NAE>-dependent oxidation of xanthine to uric acid. The enzyme also contains FAD and molybdenum. A fraction of the enzyme normally occurs in the body as xanthine oxidase, which represents an altered form of the enzyme. Xanthine oxidase uses O2 as an oxidant, rather than NAD. Xanthine oxidase converts xanthine to uric acid, and O2 to HOOH and the hydroxyl radical. 

Overproduction of uric acid can occur due to excessive de novo purine synthesis, excessive dietary purines, or the conversion of tissue nucleic acid to purine nucleotides. When these purines are metabolized, the by-products are converted to uric acid by the enzyme xanthine oxidase. Increased levels of uric acid result if the overproduction exceeds excretion. Underexcretion of uric acid can be due to defects in the renal tubular mechanisms that regulate uric acid levels in the body, causing decreased filtration, decreased secretion, or increased reabsorption. 

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