Metabolic Control of the Circulation

Liang, Chang‐seng; Lowenstein, John M.

doi:10.1172/jci109207

Cited by 123 publications

(14 citation statements)

References 37 publications

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“…These results imply that a change in AMP concentration is the primary determinant of the rate of intracellular degradation of AMP by this enzyme, since a decrease in adenylate energy charge within the physiological range is accompanied by a marked increase in AMP concentration and a much smaller decrease in the sum of the concentrations of ATP and ADP, which are activators of this enzyme (Atkinson, 1968). This is consistent with the finding by Liang & Lowenstein (1978) that the adenosine content of the myocardium and the hypoxanthine concentration in coronary blood flow in the anaesthetized dog increased under conditions of AMP accumulation induced by infusion of acetate.…”

Section: (B)supporting

confidence: 90%

Regulation of rat heart cytosol 5′-nucleotidase by adenylate energy charge

Itoh¹,

Oka²,

Ozasa³

1986

Biochemical Journal

100

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A 5'-nucleotidase (EC 3.1.3.5) was highly purified from the soluble fraction of rat heart. The preparation appeared homogeneous by the criterion of polyacrylamide-gel electrophoresis. The enzyme was activated by ATP and ADP, and inhibited by Pi. When AMP was used as substrate, the velocity/substrate-concentration plot was sigmoidal. ATP or ADP changed the plot to hyperbolic and decreased S0.5. Pi increased both the sigmoidicity of the plot and S0.5. When IMP was used as substrate, the velocity/substrate plot was hyperbolic. ATP or ADP decreased Km and increased V. Pi changed the plot to sigmoidal and increased S0.5. Within the range of adenylate energy charge observed in surviving mammalian cells (0.7-0.9), the rate of AMP-hydrolysing activity catalysed by the 5'-nucleotidase increased sharply with decreasing energy charge. The highest activity was observed at an energy-charge value of about 0.6. The response was also observed in the presence of Pi. No change in IMP-hydrolysing activity was observed in the physiological range of adenylate energy charge, but in the presence of Pi the activity gradually increased with increasing energy charge. These results suggest the possibility that this enzyme participates in production of adenosine, a vasodilator, during hypoxia and in removal of IMP, which accumulates during the hypoxia, in the heart.

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Section: (B)supporting

confidence: 90%

Regulation of rat heart cytosol 5′-nucleotidase by adenylate energy charge

Itoh¹,

Oka²,

Ozasa³

1986

Biochemical Journal

100

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“…Physiological concentrations of AMP in rat heart are in the range 0.1-0.5 mm (Williamson, 1965;Frick & Lowenstein, 1976). The AMP content of heart also rises in response to the infusion of acetate (Williamson, 1965;Liang & Lowenstein, 1978), a situation of practical interest in the case of kidney dialysis, for which acetate is currently used as the major anion in the dialysing fluid. In aerobic perfused heart, the IMP content is much lower than the AMP content.…”

Section: Discussionmentioning

confidence: 99%

5′-Nucleotidases in rat heart. Evidence for the occurrence of two soluble enzymes with different substrate specificities

Truong

Collinson

Lowenstein

1988

Biochemical Journal

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Chromatography of soluble proteins from rat heart on phosphocellulose columns separates two 5'-nucleotidases. The first to emerge from the column shows a preference for AMP over IMP as substrate, whereas the second shows a preference for IMP over AMP. The properties of the IMP-preferring enzyme, including the conditions under which it is eluted from phosphocellulose columns, show it to be the enzyme studied by Itoh, Oka & Ozasa [Biochem. J. (1986) 235, 847-851]. The kinetic properties of the AMP-preferring enzyme indicate that it is likely to be the enzyme responsible for the production of adenosine under conditions of hypoxia and increased work load, and with metabolic stresses such as a high load of acetate.

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“…These and other results have been interpreted to be due to an increased carboxylation of pyruvate to oxaloacetate brought about by increased levels of acetyl-CoA, which activates pyruvate carboxylase [32,43]. An alternative explanation was not considered, namely that acetate activation leads to an increase in the rate of AMP production [46], which results in increased adenylate deaminase activity [3] and hence in an increased rate of generation of fumarate via the purine nucleotide cycle.…”

Section: Discussionmentioning

confidence: 99%

The Purine‐Nucleotide Cycle

Aragón

Lowenstein

1980

European Journal of Biochemistry

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The contents of citric acid cycle compounds were measured in rat hind limb muscle in situ during rest, exercise, and recovery from exercise. The following changes in citric acid cycle intermediates were observed during exercise for 15 min. The contents of fumarate and malate increased fourfold over resting values. The contents of citrate, isocitrate, and succinate rose 68 'I<, 48 and 87 "' , respectively, but the increase in these intermediates was delayed relative to the increase in fumarate and malate. The content of 2-oxoglutarate did not change significantly. The content of oxaloacetate increased from less than 1 nmol/g dry weight in resting muscle to 8 nmol/g dry weight during exercise. The orthophosphate content doubled. The sum of the contents of citric acid cycle intermediates doubled. The ratios of the contents of malate/fumarate and citrate/isocitrate remained constant. The constancy of the citrate/isocitrate ratio indicates that the concentration of intracellular free Mg2+ is not affected by exercise. All metabolite levels returned to resting values during recovery. Comparison of these data with the rate of operation of the purine nucleotide cycle leads us to conclude that the increase in citric acid cycle intermediates can be accounted for by the operation of the purine nucleotide cycle.The rate of operation of the purine nucleotide cycle in skeletal muscle increases during exercise and recovery following exercise [l, 21. The cycle catalyzes the net reaction : aspartate + GTP + H20 + NH3 + fumarate + G D P + Pi. We now show that the total level of citric acid cycle intermediates in rat skeletal muscle rises by a factor of two during exercise. The changes in citric acid cycle intermediates are compared with the rate of formation of IMP in the absence and presence of hadacidin, an inhibitor of adenylosuccinate synthetase. On the basis of this comparison it is concluded that the operation of the purine nucleotide cycle is sufficient to account for the observed increases in citric acid cycle intermediates in skeletal muscle. Other possible reactions for replenishing or increasing citric acid cycle intermediates are considered in the Discussion.ions participate in the reactions of the citric acid and the purine nucleotide cycles and they exert direct and indirect effects on adenylate deaminase [3]. Determinations of the contents of these substances in skeletal muscle during rest, exercise, and recovery from exercise are also presented. Orthophosphate and Mg2 MATERIALS AND METHODSMale rats of the Sprague-Dawley strain were obtained from Charles River Breeding Laboratories (Wilmington, MA). The animals received food and water ad libitum, and weighed 175-200 g at the time of use.Rats were anaesthetized by intraperitoneal injection of sodium pentobarbital (5 mg/100 g body weight) and the skin from the right hind leg was removed. The sciatic nerve was exposed and a Dastre's electrode (Palmer Co., London, UK) was attached around the nerve in its gluteal course. The leg was fixed to a platform at the ankle with ...

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Metabolic Control of the Circulation

Cited by 123 publications

References 37 publications

Regulation of rat heart cytosol 5′-nucleotidase by adenylate energy charge

Regulation of rat heart cytosol 5′-nucleotidase by adenylate energy charge

5′-Nucleotidases in rat heart. Evidence for the occurrence of two soluble enzymes with different substrate specificities

The Purine‐Nucleotide Cycle

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