Hypoxanthine-3 -oxide

Hypoxanthine 3-oxide Xanthine Ac20/(CF3C0)20 69BO750... 

Hypoxanthine 3-oxide Guanine Pyridine/AcOH (several hours) + aq. NaOH 69Ba750... 

Hypoxanthine 3-oxide 2,6-Dichloropurine+a little 6,8-dichloropurine POCls/heat 69Ba750... 

Hypoxanthine 3-oxide Xanthine AC20/(CF3C0)20 69BCJ750... 

Other published statements about the chemical nature of alarm pheromone are not sufficiently precise to provide information on potential non-alarm functions. These include the statement by Ahsan and Prasad (1982) that the alarm pheromone is a polypeptide or protein molecule and the suggestion by Tucker and Suzuki (1972) that the alarm pheromone may be a mixture of peptides, amino acids and derivatives. Similarly Lebedeva et al. (1975) isolated active fractions from minnow skin (Phoxinus phoxinus) but did not identify specific compounds although they found the molecular weight of their active components to be over 950, well above the molecular weight of hypoxanthine-3-oxide. Kasumyan and Lebedeva (1977, 1979) similarly do not provide sufficient detail about the fractions isolated to allow conclusions about other functions for alarm substance. 

FIGURE 2.1 Hypoxanthine oxide, a fish alarm pheromone. 

Adrenaline was oxidised to adrenochrome by xanthine oxidase in the presence of a normal substrate for this enzyme, such as hypoxanthine, at pH 7.4 [112, 113]. Adrenaline was not oxidised, however, by either the enzyme or the substrate alone. Neither was oxidation observed in the presence of uric acid, the end product of hypoxanthine oxidation, either with or without... 

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. 

Xanthine oxidase, mol wt ca 275,000, present in milk, Hver, and intestinal mucosa (131), is required in the cataboHsm of nucleotides. The free bases guanine and hypoxanthine from the nucleotides are converted to uric acid and xanthine in the intermediate. Xanthine oxidase cataly2es oxidation of hypoxanthine to xanthine and xanthine to uric acid. In these processes and in the oxidations cataly2ed by aldehyde oxidase, molecular oxygen is reduced to H2O2 (133). Xanthine oxidase is also involved in iron metaboHsm. Release of iron from ferritin requires reduction of Fe " to Fe " and reduced xanthine oxidase participates in this conversion (133). 

As an inhibitor of xanthine oxidase, allopurinol also markedly decreases oxidation of both hypoxanthine and xanthine itself to the sole source of uric acid (19) in man. This metabolic block thus removes the source of uric acid that in gout causes the painful crystalline deposits in the joints. It is of interest that allopurinol itself is oxidized to the somewhat less effective drug, oxypurinol (21), by xanthine oxidase. 

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. 

XOD is one of the most complex flavoproteins and is composed of two identical and catalytically independent subunits each subunit contains one molybdenium center, two iron sulfur centers, and flavine adenine dinucleotide. The enzyme activity is due to a complicated interaction of FAD, molybdenium, iron, and labile sulfur moieties at or near the active site [260], It can be used to detect xanthine and hypoxanthine by immobilizing xanthine oxidase on a glassy carbon paste electrode [261], The elements are based on the chronoamperometric monitoring of the current that occurs due to the oxidation of the hydrogen peroxide which liberates during the enzymatic reaction. The biosensor showed linear dependence in the concentration range between 5.0 X 10 7 and 4.0 X 10-5M for xanthine and 2.0 X 10 5 and 8.0 X 10 5M for hypoxanthine, respectively. The detection limit values were estimated as 1.0 X 10 7 M for xanthine and 5.3 X 10-6M for hypoxanthine, respectively. Li used DNA to embed xanthine oxidase and obtained the electrochemical response of FAD and molybdenum center of xanthine oxidase [262], Moreover, the enzyme keeps its native catalytic activity to hypoxanthine in the DNA film. So the biosensor for hypoxanthine can be based on... 

Uric acid is the end-product of purine metabolism in humans, other primates, birds and reptiles. It is produced in the liver by the oxidation of xanthine and hypoxanthine (Figure 12.16),... 

FIGURE 1 7-3 Adenosine metabolites. Adenosine is converted to inosine by adenosine deaminase. Removal of the ribose by nucleoside phos phorylase produces hypoxanthine, which is sequentially oxidized to xanthine and uric acid by xanthine oxidase. 

Fig. 2.2 Schematic diagram showing XOR-catalysed oxidation of hypoxanthine and xanthine (also most reducing substrates) at the molybdenum (Mo) site, and ofNADH at the FAD site. Reduction of NAD+ or of molecular oxygen takes place at FAD. Adapted from Harrison [73],...

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). 

The oxidative reaction catalyzed by XOR is unusual relative to most oxidative enzymes, certainly P450, in that a molecule of water is the source of the oxygen atom that is transferred to hypoxanthine rather than a molecule of oxygen (90). This means that the overall reaction provides electrons rather than consuming them. The stoichiometry... 

FIGURE 4.36 Xanthine oxidase-mediated oxidation of hypoxanthine to uric acid. 

The pyrazolo[3, 4-d] pyrimidines are substrates for and inhibitors of xanthine oxidase [266, 267]. 4-Hydroxypyrazolo[3,4-d] pyrimidine was first investigated for its ability to protect 6-mercaptopurine and other analogues from oxidation by xanthine oxidase [384], but it also inhibits the oxidation of the natural purines, hypoxanthine, and xanthine. Its profound effect on uric acid metabolism made it an obvious choice for the treatment of gout and its utility in the control of this disease has been demonstrated [385, 386]. 

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. 

The answer is c. (Hardman, pp 649-650.) Acute hyperuricemia, which often occurs in patients who are treated with cytotoxic drugs for neoplasic disorders, can lead to the deposition of urate crystals in the kidneys and their collecting ducts. This can produce partial or complete obstruction of the collecting ducts, renal pelvis, or ureter. Allopurinol and its primary metabolite, alloxanthine, are inhibitors of xanthine oxidase, an enzyme that catalyzes the oxidation of hypoxanthine and xanthine to uric acid. The use of allopurinol in patients at risk can markedly reduce the likelihood that they will develop acute uric acid nephropathy. 

Oxidation of xanthine and hypoxanthine Xanthine and hypoxanthine can he oxidized enzymatically with xanthine oxidase to produce uric acid. 

Dietary purines are not an important source of uric acid. Quantitatively important amounts of purine are formed from amino acids, formate, and carbon dioxide in the body. Those purine ribonucleotides not incorporated into nucleic acids and derived from nucleic acid degradation are converted to xanthine or hypoxanthine and oxidized to uric acid (Figure 36-7). Allopurinol inhibits this last step, resulting in a fall in the plasma urate level and a decrease in the size of the urate pool. The more soluble xanthine and hypoxanthine are increased. 

---