Xanthine oxidase regulation

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. 

Stirpe, F. and Della Corte, E. (1969). The regulation of rat liver xanthine oxidase. Conversion in vitro of the enzyme activity from dehydrogenase (type D) to oxidase (type O). J. Biol.Chem. 244, 3855-3863. 

O Donnell et al. [70] found that LOX and not cyclooxygenase, cytochrome P-450, NO synthase, NADPH oxidase, xanthine oxidase, ribonucleotide reductase, or mitochondrial respiratory chain is responsible for TNF-a-mediated apoptosis of murine fibrosarcoma cells. 15-LOX activity was found to increase sharply in heart, lung, and vascular tissues of rabbits by hypercholesterolemia [71], Schnurr et al. [72] demonstrated that there is an inverse regulation of 12/15-LOXs and phospholipid hydroperoxide glutathione peroxidases in cells, which balanced the intracellular concentration of oxidized lipids. 

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. 

From our study and from the results of BRADFORD Cl968) on the important daily turnover of hypoxanthine in xanthine oxidase deficiency, we would like to say that deficiency ( or inhibition by alio or oxipurinol ) of xanthine oxidase activity should be an important factor in the regulation of de novo biosynthesis of uric acid, (over productor with normal HGPRT activity). 

Resveratrol can also prevent the initial events of atherosclerosis in endothelial cells by inhibition of the enzymatic systems producing reactive oxygen species, such as NADPH oxidase and hypoxanthine/xanthine oxidase, and by the inhibition of both the expression of adhesion molecules and the monocyte adhesion to endothelial cells [167]. Moreover, red wine polyphenols, in particular E-resveratrol, have been shown to inhibit the proliferation and the migration of vascular smooth muscle cells in intima, notably involved in the formation of atherosclerotic plaques [173]. In fact, resveratrol specifically blocks the mTOR pathway, which is activated by oxidized LDL, and regulates the proliferation of smooth muscle cells [174]. Other stilbenoids have been shown to exert an activity on this target as well. For example, pterostilbene inhibits vascular smooth muscle cell proliferation... 

Treatment with metabolic inhibitors. For example allopiuinol which inhibits xanthine oxidase, an enzyme responsible for the oxidation of purines, has been used to regulate uric acid production in gout. 

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