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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of 5'-nucleotidase and AMP-deaminase to adenine nucleotide degradation in human cardiomyocytes isolated from diseased or normal heart was investigated. The preparation used contained 30 to 50% of viable cells and the nucleotide degradation was stimulated by addition of deoxyglucose and oligomycin. To distinguish pathways of nucleotide degradation, adenosine deaminase was inhibited by erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA). Under these conditions, ATP concentration was decreased by 60% after 45 min of incubation. Simultaneously, increases in intra- and extracellular catabolite concentrations have been observed. Adenosine was the predominant catabolite found in both the cells and in the extracellular medium accounting for more than 70% of all degradation products. Intracellular adenosine concentration rose to 300 times greater than that outside the cell. An increase in intra- and extracellular inosine was also seen. Only a small increase of IMP concentration was observed. No hypoxanthine accumulation was found. No significant change in initial adenine nucleotide concentrations were observed in isolated cells during aerobic incubation without deoxyglucose and oligomycin. In conclusion, a pathway involving adenosine production appears to be the principal route of nucleotide degradation in human cardiomyocytes.
J Mol Cell Cardiol 1992 Jan
PMID:Adenine nucleotide catabolism and adenosine formation in isolated human cardiomyocytes. 156 34

Our earlier work on reperfusion showed that adult rat hearts released almost twice as much purine nucleosides and oxypurines as newborn hearts did [Am J Physiol 254 (1988) H1091]. A change in the ratio anabolism/catabolism of adenosine could be responsible for this effect. We therefore measured the activity of adenosine kinase, adenosine deaminase, nucleoside phosphorylase and xanthine oxidoreductase in homogenates of hearts and myocytes from neonatal and adult rats. In hearts the activity of adenosine deaminase and nucleoside phosphorylase (10-20 U/g protein) changed relatively little. However, adenosine kinase activity decreased from 1.3 to 0.6 U/g (P less than 0.025), and xanthine oxidoreductase activity increased from 0.02 to 0.85 U/g (P less than 0.005). Thus the ratio in activity of these rate-limiting enzymes for anabolism and catabolism dropped from 68 to 0.68 during cardiac development. In contrast, the ratio in myocytes remained unchanged (about 23). The large difference in adenosine anabolism/catabolism ratio, observed in heart homogenates, could explain why ATP breakdown due to hypoxia is lower in neonatal than in adult heart. Because this change is absent in myocytes, we speculate that mainly endothelial activities of adenosine kinase and xanthine oxidoreductase are responsible for this shift in purine metabolism during development.
J Mol Cell Cardiol 1990 Oct
PMID:Ischemic nucleotide breakdown increases during cardiac development due to drop in adenosine anabolism/catabolism ratio. 209 32

The isolated perfused rat heart was used to study the influence of adenine nucleotides and their metabolites on vulnerability to ventricular fibrillation. In this model the incidence of ventricular arrhythmias after coronary artery ligation is determined by the extracellular K+ concentration; with perfusate K+ of 2.0 and 3.0 mmol/l hearts develop a high incidence of ventricular arrhythmias and fibrillation while arrhythmias are not encountered with perfusate K+ of 9.0 mmol/l. Assay of adenine nucleotides in uninvolved and ischaemic myocardium of these hearts showed a direct relationship between incidence of ventricular fibrillation and tissue levels of cyclic AMP but not tissue levels of lactate, high energy phosphates, adenosine, inosine and hypoxanthine/xanthine. Administration of dibutyryl cyclic AMP to isolated rat hearts reduced the ventricular fibrillation threshold; this action of cyclic AMP was effectively antagonized by adenosine and its N-ethylcarboxamido analogue but not by 2-chloroadenosine, phenylisopropyladenosine, cyclohexyladenosine and the adenosine deaminase inhibitor, EHNA. 2-Chloroadenosine, like adenosine, inhibited the increase in heart rate caused by DBcAMP. All the adenosine analogues had antiarrhythmic activity against spontaneously occurring ventricular arrhythmias during coronary artery occlusion. Adenosine analogues also antagonized the effect of dibutyryl cyclic AMP whereby it prolongs the QT interval. Adenosine, by as yet incompletely defined mechanisms, may act as an antagonist to the cyclic AMP mediated increase in vulnerability which contributes to the genesis of ventricular fibrillation in the early phase of myocardial ischaemia.
J Mol Cell Cardiol 1987 Oct
PMID:Adenine nucleotides and ventricular fibrillation. 244 89

The transmural distribution of the adenosine-generating enzyme 5'-nucleotidase (5'N) and of the adenosine-degrading enzymes adenosine deaminase (ADA), AMP deaminase (AMP-D) and adenosine kinase (Ado-K) were determined across the walls of left and right ventricles of control and hypertrophic rat hearts. The enzyme distribution across the left ventricle wall (but not across the right wall) of normal hearts was not uniform: 5'N activity shows its highest levels in the subepicardial and in the subendocardial regions, whereas all the other enzyme activities show their lowest levels. A similar pattern of transmural distribution was also detected in other mammalian species (ox and pig). In the experimental cardiac hypertrophy, caused by two different types of chronic cardiac overload, the levels and the profiles of transmural distribution of 5'N and ADA enzyme activities may significantly change across the rat left ventricle wall.
Basic Res Cardiol
PMID:The regional distribution of adenosine-regulating enzymes in the left and right ventricle walls of control and hypertrophic heart. 255 11

The S-adenosylhomocysteine (SAH) hydrolase inhibitor adenosine dialdehyde was used in isolated guinea pig hearts to determine the contribution of the transmethylation pathway to cardiac adenosine formation. This inhibitor did not alter cardiac hemodynamics but effectively inhibited SAH-hydrolase activity under in vitro and in vivo conditions. In normoxic perfused hearts adenosine dialdehyde (10 microM) caused tissue levels of SAH to linearly increase at a rate of 160 pmol/g/min over 60 min. At the same time adenosine dialdehyde decreased release of adenosine into the coronary effluent perfusate by 16 pmol/min (34%). Hypoxic perfusion (30% O2) of guinea-pig hearts increased release of adenosine from 43 to 3700 pmol/min. However, rate of SAH formation in the presence of adenosine dialdehyde was only slightly enhanced from 160 to 200 pmol/g/min and adenosine dialdehyde did not significantly alter the hypoxia induced adenosine release. Since all experiments were performed in the presence of the adenosine deaminase inhibitor EHNA (5 microM) the results demonstrate: (1) the transmethylation pathway of the heart contributes one third to global cardiac adenosine production under normoxic conditions and provides a constant source of adenosine independent of tissue oxygenation. (2) The majority of SAH-derived adenosine is salvaged most likely via adenosine kinase. (3) The hypoxia induced adenosine production is predominantly derived from enhanced 5' AMP hydrolysis.
J Mol Cell Cardiol 1989 Aug
PMID:Contribution of S-adenosylhomocysteine to cardiac adenosine formation. 277 14

The activities of the adenosine-generating enzyme 5'-nucleotidase and the adenosine-degrading enzyme adenosine deaminase were determined for four regions of rat hearts prior to and following 10-60 min of ischaemia. Whereas adenosine deaminase was uniformly active throughout the heart, 5'-nucleotidase was twice as active in atrial than in ventricular myocardium, and more active in the right than in the left ventricles in normoxic tissues. In isolated heart preparations normoxic perfusion decreased adenosine deaminase and increased 5'-nucleotidase activity compared to levels in vivo. Global ischaemia for 10 min elevated adenosine deaminase activity but had no effect on 5'-nucleotidase activity. However, 30 min of ischaemia decreased 5'-nucleotidase activity by 50% in all regions of the heart. These changed levels were not altered by 10 min of reperfusion. The fall in 5'-nucleotidase activity with ischaemia occurred only in the 90% of this enzyme which is membrane-bound. The reasons for the marked differences in distribution and responses to ischaemia of these two enzymes have yet to be elucidated but metabolic inhibitors seem unlikely to be involved.
Basic Res Cardiol
PMID:Differences in the regional distribution and response to ischaemia of adenosine-regulating enzymes in the heart. 282 14

The purpose of this study was to determine whether adenosine or the adenosine deaminase-resistant analogue, N6-R-1-phenyl-2-propyladenosine (RPIA), could slow the rate of spontaneous ventricular tachycardia occurring 24 hours after left anterior descending coronary artery occlusion. Chloralose-anesthetized, open chest dogs (n = 25) with ventricular tachycardia were studied. The left anterior descending artery was cannulated distally. Intracoronary infusions of adenosine, 10(-7) to 10(-5) M, did not alter the rate of ventricular tachycardia. Ventricular tachycardia slowed by 4.6% with adenosine, 10(-4) M. RPIA, 10(-6) to 10(-4) M, produced a concentration-dependent decrease in the rate of ventricular tachycardia when injected into the left anterior descending coronary artery. This effect of RPIA was reversed by the adenosine antagonist aminophylline, 10(-5) M. After bilateral stellate ganglionectomy, RPIA, 10(-5) M, did not, but metoprolol, 0.5 mg, did slow ventricular tachycardia after intracoronary injection. However, RPIA, 10(-5) M, produced a 43% decrease in the increment in ventricular tachycardia occurring during sympathetic neural stimulation. Therefore, when injected into the left anterior descending artery, adenosine, 10(-4) M, and RPIA, 10(-6) to 10(-4) M, decrease the rate of ventricular tachycardia in 24 hour old myocardial infarction. Furthermore, this decrease in the rate of ventricular tachycardia is the result of prejunctional sympathetic antagonism.
J Am Coll Cardiol 1987 Aug
PMID:Autonomic control of ventricular tachycardia. III. Effects of adenosine and N6-R-1-phenyl-2-propyladenosine. 295 25

Activities of several adenosine metabolizing enzymes were examined in capillary preparations isolated from rabbit ventricle. Vmax and Km values for 5'-nucleotidase were 2.3 nmol/min/mg and 10 microM, respectively. For adenosine deaminase the corresponding values were 7.8 nmol/min/mg and 32 microM. S-adenosyl-homocysteine hydrolase, which forms adenosine by the hydrolysis of S-adenosylhomo-cysteine, was also present (Vmax, 0.07 nmol/min/mg; Km, 0.81 microM), as were adenosine kinase (Vmax, 0.2 nmol/min/mg; Km, 0.52 microM) and purine nucleoside phosphorylase (Vmax, 13.8 nmol/min/mg; Km, 96 microM). These enzymes were also present in microvessels (capillaries and arterioles) purified from rabbit brain. Activities of several enzymes, especially 5'-nucleotidase and adenosine deaminase, were much lower in myocytes isolated from rabbit ventricle. The study provides evidence that endothelial cells of the microvasculature from heart and brain are capable of activity forming and degrading adenosine. It is possible that adenosine formed by these cells may contribute to the local regulation of blood flow.
J Mol Cell Cardiol 1986 Jan
PMID:Adenosine metabolism in microvessels from heart and brain. 300 95

The loss of the catabolic products of adenosine triphosphate in the form of purine nucleosides and oxypurines during ischemia and subsequent reperfusion may limit adenine nucleotide regeneration. This study compared the effects of infusion of inhibitors of the major reactions involved in the degradation of adenosine triphosphate to inosine on the postischemic recovery of high energy phosphate and myocardial function. Inhibitors of adenylate kinase, 5'nucleotidase, adenosine translocase and adenosine deaminase were studied. Following 30 minutes of ischemia, only hearts infused with alpha, beta, methylene adenosine diphosphate (5' nucleotidase inhibitor) recovered significantly better ventricular function than control (p less than 0.05), but all hearts had increased adenosine triphosphate regeneration (p less than 0.05). The formation and washout of greater than 30% of the total adenine pool metabolites was not prevented by any drug. Nevertheless all manipulations of adenine metabolism resulted in recruitment of high energy phosphate during preischemic infusion.
J Mol Cell Cardiol 1986 Oct
PMID:The influence of inhibitors of the ATP degradative pathway on recovery of function and high energy phosphate after transient ischemia in the rat heart. 302 47

In this study evidence is provided to suggest that nucleoside formation with hypoxia in myocardial tissue from the guinea-pig follows a different course from that in the rat, rabbit or dog. 1) After ischemia, tissue levels of adenosine remain barely detectable in the guinea-pig but rise considerably in the rat and the dog. 2) IMP, remaining almost absent in the dog, does not change in the rat but strongly increases (X 6) in the guinea-pig heart with ischemia. 3) Mioflazine, a nucleoside transport inhibitor, completely reverses the ratio adenosine/inosine in dog myocardium after 8 min of ischemia, making adenosine by far the major nucleoside. No effect could be detected in the guinea-pig. 4) In contrast with the rat and rabbit, ischemia in the guinea-pig does not lead to any considerable release of adenosine upon reperfusion. 5) In the rabbit, the presence of a nucleoside transport inhibitor completely reverses the adenosine/inosine ratio in reperfusates after ischemia. Although the release is strongly inhibited under these conditions in the guinea-pig, adenosine release remains negligible when compared with inosine. 6) Even in the presence of high concentrations of an adenosine deaminase inhibitor, inosine remains the major metabolite released upon reperfusion after ischemia, in the guinea-pig heart.
Basic Res Cardiol
PMID:Formation and release of nucleosides in the ischemic myocardium. Is the guinea-pig the exception? 409 81


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