Purine catabolism in man: inhibition of 5′-phosphomonoesterase activities from placental microsomes

Fox, Irving H.; Marchant, Pamela J.

doi:10.1139/o76-154

Cited by 18 publications

(7 citation statements)

References 9 publications

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“…The kinetic behaviour of purified 5'-N was similar to that described for the enzyme from various mammalian and fowl tissues and microorganisms. In fact, the K , value was close to that obtained by other authors (Ipata, 1968;Depierre and Karnowsky, 1974;Burger and Lowenstein, 1975;Fox and Marchant, 1976;Brake et al, 1978) as were the results relating to optimum pH (Song and Bodansky, 1966;Ipata, 1968;Evans and Gurd, 1973;Nakamura, 1976;Ahlers et al, 1978;Ozaki and Shiio, 1979), product inhibition (Ozaki and Shiio, 1979), substrate inhibition (Evans and Gurd, 1973), and activation energy (Levin and Bodansky, 1966;Brake et al, 1978). The presence of Mg (11) did not modify the activity of purlfied 5'-N or the pH curve, in agreement with what has been described for the enzyme from several mammals (Nakamura, 1976;Dornand et al, 1978) and microorganisms (Ahlers et al, 1978;Ozaki and Shiio, 1979).…”

Section: Discussionsupporting

confidence: 90%

Purification and Characterization of Bovine Brain 5′‐Nucleotidase

Montero¹,

Fes²

1982

Journal of Neurochemistry

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The 5'-nucleotidase located in the cytoplasmic fraction of bovine brain cortex was purified to electrophoretic homogeneity. The molecular weight was 134,000 daltons in the presence of sodium deoxycholate, whereas the enzyme formed high molecular weight aggregates in the absence of detergent. The purified enzyme showed the same kinetic and electrophoretic behaviour as the enzyme present in the original cytoplasmic fraction, and the presence of surfactants did not change the Km and Vm values. The nucleotidase from this source was a phosphohydrolase of 5'-mononucleotides acting on the deoxyribonucleotides and ribonucleotides of purines and pyrimidines. 5'-IMP was the preferred substrate; the optimum pH was 7.5. The study of the influence of the temperature on the initial reaction rates allowed calculation of the delta Ea and delta H degrees values. The variation of Vm and Km with a change in pH suggests the existence of a sulfhydryl group and an imidazole group in the enzyme-substrate complex.

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Section: Discussionsupporting

confidence: 90%

Purification and Characterization of Bovine Brain 5′‐Nucleotidase

Montero¹,

Fes²

1982

Journal of Neurochemistry

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“…The brain even more than other tissues recycles hypoxanthine and converts it into purine nucleotides (5 1). In addition, allopurinol ribonucleotide, a metabolite of allopurinol, inhibits 5' nucleotidase, the enzyme that catalyzes the dephosphorylation of AMP (52). These findings suggest that allopurinol may have enhanced the preservation of adenine cerebral nucleotides, including ATP, during both hypoxia-ischemia and recovery in addition to its inhibition of xanthine oxidase activity.…”

Section: Discussionmentioning

confidence: 92%

Reduction of Perinatal Hypoxic-Ischemic Brain Damage with Allopurinol

1990

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ABSTRACT. Cytotoxic free radicals are generated during cerebral hypoxia-ischemia and reperfusion. We studied the efficacy of allopurinol, a xanthine oxidase inhibitor and free radical scavenger, in reducing posthypoxic-ischemic damage in the developing brain of 7-d-old rat pups. Hypoxic-ischemic injury to the right cerebral hemisphere was produced by ligation of the right common carotid artery followed by 3 h of hypoxia with 8% oxygen. Thirty to 45 min before the hypoxia, the rats received either allopurinol Free radicals contribute to the pathogenesis of hypoxicischemic brain damage (1-5), and successful management of traumatic or ischemic brain injury includes prevention of free radical damage (6-10).During cerebral hypoxia-ischemia, tissue stores of ATP are degraded sequentially to ADP, AMP, adenosine, inosine, and hypoxanthine (1 I, 12). Hypoxanthine levels accumulate as further metabolism is impeded by tissue hypoxia (13, 14). During reperfusion and reoxygenation, there is a transient rise in xanthine with a concomitant fall in hypoxanthine, reflecting the conversion of hypoxanthine to xanthine by the enzyme xanthine oxidase (1 5). This reaction generates superoxide and secondarily derived cytotoxic species including hydroxyl radicals (2). Free radicals are highly reactive molecules capable of damaging cells by peroxidation of membrane phospholipids (16) and by oxidation of cellular proteins and nucleic acids (17).Allopurinol is both an inhibitor of xanthine oxidase (1 8) and a scavenger of free radicals (19, 20). It has been used successfully to reduce ischemic injury of the heart (21), kidney (22), small intestine (23), and adult rat brain (24, 25). Accordingly, we aimed to establish if allopurinol could reduce hypoxic-ischemic injury to the developing brain of the 7-d-old rat pup. MATERIALS AND METHODSTo evaluate the potential neuroprotective effect of allopurinol, we studied 7-d postnatal rat pups in which we induced a hypoxicischemic insult to the right cerebral hemisphere (see below). Animals were killed after either a short (42 h) or long (30 d) period of recovery to evaluate the extent of the lesion.Animals in the short recovery study were evaluated for brain water content, whereas those in the long recovery study were killed after 30 d of age to evaluate long-term neuropathologic alterations. The rat pups were treated alternately with either saline or allopurinol (see below).Animal model. Seven-d-old Wistar (Charles River, Wilmington, MA) rat pups of either sex, weighing between 12-18 g were anesthetized with a mixture of halothane (4% halothane, 1-1.5% for maintenance), 30% oxygen, and balance nitrous oxide. The right common carotid artery of each pup was ligated with 4-0 surgical silk. The wound was then sutured and the animal allowed to recover. The duration of anesthesia was about 5 min. After surgery, the rat pups were returned to their dams for 2' /2 h. Pups from mixed litters were then randomly divided into two equal treatment groups. One group received an injection of normal saline (0.2 mL)...

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“…33 Allopurinol also has a potential to prevent the irreversible loss of ATP by inhibition of 5Ј-nucleotidase and facilitate mitochondrial electron transport. [36][37][38] All of these mechanisms may be involved in the inhibitory effect of allopurinol on radical formation.…”

Section: Effect Of Allopurinol On Free Radical Generationmentioning

confidence: 99%

Effect of Allopurinol Pretreatment on Free Radical Generation after Primary Coronary Angioplasty for Acute Myocardial Infarction

Guan

Osanai

Kamada

et al. 2003

Journal of Cardiovascular Pharmacology

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Allopurinol, an inhibitor of xanthine oxidase, was shown to improve the regional ventricular function after coronary artery occlusion and reperfusion in animal models. The effects of oral administration of allopurinol on a transient increase in free radical generation after primary percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI) and on their clinical outcomes were examined. Thirty-eight AMI patients undergoing primary PTCA were randomly assigned to control (group 1, n = 20) and allopurinol treatment groups (group 2, n = 18). Allopurinol (400 mg) was administered orally just after the admission (approximately 60 min before reperfusion). Free radical production was assessed by successive measurement of urinary excretion of 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) after PTCA. Urinary 8-epi-PGF(2alpha) excretion was increased by twofold at 60-90 min after PTCA compared with the baseline value in group 1. This increase was completely inhibited in group 2. Plasma allopurinol concentration was 1,146 +/- 55 ng/ml in group 2 when reperfusion was achieved. Slow flow in the recanalized coronary artery after PTCA occurred less frequently in group 2 than in group 1. Cardiac index determined just after reperfusion and left ventricular ejection fraction at 6 months after PTCA were both significantly greater in group 2 than in group 1 although pulmonary capillary wedge pressure was similar in the two groups. In conclusion, allopurinol pretreatment is effective in inhibiting generation of oxygen-derived radicals during reperfusion therapy and the recovery of left ventricular function in humans.

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Purine catabolism in man: inhibition of 5′-phosphomonoesterase activities from placental microsomes

Cited by 18 publications

References 9 publications

Purification and Characterization of Bovine Brain 5′‐Nucleotidase

Purification and Characterization of Bovine Brain 5′‐Nucleotidase

Reduction of Perinatal Hypoxic-Ischemic Brain Damage with Allopurinol

Effect of Allopurinol Pretreatment on Free Radical Generation after Primary Coronary Angioplasty for Acute Myocardial Infarction

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