Xanthine oxidase pathway

Athar M, Elmets C A, Bickers D R, et al. (1989). A novel mechanism for the generation of superoxide anions in hematoporphyrin derivativemediated cutaneous photosensitization. Activation of the xanthine oxidase pathway. J. Clin. Invest. 83 1137-1143. 

During ischaemia, the activity of cellular antioxidant systems may be reduced (Ferrari et al. 1985 GaUnanes etal. 1992). In addition, a number of cellular pathways that produce free radicals are primed during ischaemia such as the xanthine/xanthine oxidase system (McCord, 1987), catecholamine auto-oxidation (Jackson et al., 1986) and the arachadonic acid pathway (Halliwell and Gutteridge, 1989). Thus, during early reperfusion there is a burst of free radical production (see Fig. 4.1) that may overwhelm the antioxidant systems of the cells. 

Other enzyme systems may also be directly or indirectly involved in the generation of ROS in the lung, including those of the eicosanoid pathway, the mitochondrial electron transport system, and aldehyde, glucose and xanthine oxidases (Parks and Granger, 1986). These systems may also be relevant to lung damage. For example, the oedematous pulmonary injury that results from cessation of blood flow for a period followed by reinstatement of... 

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-... 

Zhang, Z., Naughton, D., Winyard, P. G., Benjamin, N., Blake, D. R., Symons, M. C. R., Generation of nitric oxide by a nitrite reductase activity of xanthine oxidase a potential pathway for nitric oxide formation in the absence of nitric oxide synthase activity. Biochem. Biophys. Res. Commun. 249 (1998), p. 767—772... 

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. 

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... 

Purine nucleotides are degraded by a pathway in which they lose their phosphate through the action of 5 -nucleotidase (Fig. 22-45). Adenylate yields adenosine, which is deaminated to inosine by adenosine deaminase, and inosine is hydrolyzed to hypoxanthine (its purine base) and D-ribose. Hypoxanthine is oxidized successively to xanthine and then uric acid by xanthine oxidase, a flavoenzyme with an atom of molybdenum and four iron-sulfur centers in its prosthetic group. Molecular oxygen is the electron acceptor in this complex reaction. 

Purine nucleotides are converted to uric acid by a pathway that removes amino groups and ribose 1-phosphate from the nucleotide, then uses xanthine oxidase to oxidize the carbon rings to uric acid. Allopurinol, a drug that inhibits xanthine oxidase, is used to treat gout. 

Shown in Figures 5-7 are the redox pathways for xanthine oxidase, sulfite oxidase, and nitrate reductase (assimilatory and respiratory), respectively. These schemes address the electron and proton (hydron) flows. The action of the molyb-doenzymes is conceptually similar to that of electrochemical cells in which half reactions occur at different electrodes. In the enzymes, the half reactions occur at different prosthetic groups and intraprotein (internal) electron transfer allows the reactions to be coupled (i.e., the circuit to be completed). In essence, this is the modus operandi of these enzymes, which must be determined before intimate mechanistic considerations are seriously addressed. 

Ascorbic Acid (AA). Experimental (SI, S7, S24) and clinical (B13, B17) studies have provided some evidence for the concept that oxidative stress is the common pathway for the initiation of AP (B14). The most abundant endogenous antioxidant in the aqueous phase is ascorbic acid (AA), a bioactive form of vitamin C, which scavenges oxygen-derived free radicals produced by activated neutrophils and the hypoxanthine-xanthine oxidase system (D12). Scott et al. 

Allopurinol is a drug given to gout sufferers. It inhibits an enzyme of the purine degradation pathway called xanthine oxidase by acting in the capacity of a substrate. However, its product, oxidized allopurinol, is not able to leave the active site of the enzyme, thus blocking it. Is there a name for this type of substrate What inhibition kinetics would you observe with a Lineweaver-Burk plot, and why ... 

The urinary caffeine test is not based on assays of specific substrates and products of NAT2 ( including other metabolism pathways involving at least xanthine-oxidases), and is affected by diet habits, xanthine-oxidase inhibitors such as allopurinol (Fuchs 1999), or other drugs (Klebovitch 1995). NAT activities are affected by anti-inflammatory drugs. Of note, acetominophen is an inhibitor of NAT2 in vivo (Rothen 1998). 

The salvage pathway does not involve the formation of new heterocyclic bases but permits variation according to demand of the state of the base (B), i.e. whether at the nucleoside (N), or nucleoside mono- (NMP), di- (NDP) or tri- (NTP) phosphate level. The major enzymes and routes available (Scheme 158) all operate with either ribose or 2-deoxyribose derivatives except for the phosphoribosyl transferases. Several enzymes involved in the biosynthesis of purine nucleotides or in interconversion reactions, e.g. adenosine deaminase, have been assayed using a method which is based on the formation of hydrogen peroxide with xanthine oxidase as a coupling enzyme (81CPB426). 

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