Citrate synthase from Crithidia fasciculata: Inhibition by adenine nucleotides and suramin

Salvarrey, Marcela S.; Cazzulo, Juán José

doi:10.1016/0305-0491(82)90029-3

Cited by 4 publications

(1 citation statement)

References 9 publications

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“…Therefore, the other inhibitory site may lie in the pathway of utilization of acetyl-CoA in the tricarboxylic acid cycle. A slight inhibition of purified citrate synthase from Crithidia fasciculata, which condenses acetyl-CoA with oxaloacetate, has been reported (26). Larger inhibition of the .in vivo enzyme cannot, however, be excluded.…”

Section: Discussionmentioning

confidence: 99%

Effects of Ammonium Chloride, Salicylate, and Carnitine on Palmitic Acid Oxidation in Rat Liver Slices

Maddaiah

Miller

1989

Pediatr Res

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ABSTRACT. To explore the possible association of hyperlipidemia with hyperammonemia and aspirin ingestion, the effects of NH4+, salicylate, and carnitine on the oxidation of [l-'4C]palmitic acid to acid-soluble products (ASP) and to C 0 2 were investigated in rat liver slices. DL-carnitine (5 mM) increased total oxidation (ASP + C02) more than oxidation to C02. KCN (1.5 mM) inhibited more than 90% of the oxidation. N&CI inhibited the oxidation that reached a maximum at about 40 mM, but the inhibition of oxidation to COz (63%) was larger than that of total oxidation (30%). Carnitine did not influence NH4+ inhibition, which is consistent with the results reported for isolated mitochondria. Salicylate effects depended on salicylate concentration as well as on the presence of carnitine. In the absence of carnitine, inhibition of total oxidation reached 90% at 3 mM salicylate but that of oxidation to C 0 2 reached 50%. Velocity calculated at saturating palmitic acid concentration for total oxidation was slightly increased by 0.75 mM salicylate, but the increase for oxidation to C 0 2 was larger. At 3 mM salicylate, velocity at saturating palmitic acid concentration for the oxidation was decreased, but the decrease for oxidation to COz was smaller than for total oxidation. Carnitine partially relieved the inhibition of total oxidation and further increased the formation of COz. The combination of 20 mM NKCI and 0.75 rnM salicylate inhibited total oxidation, which was more than additive of the individual effects, and carnitine partially relieved the inhibition. It is concluded that NH4+ exerted a stronger inhibition of oxidation to COZ than of oxidation to ASP, whereas salicylate strongly inhibited the oxidation to ASP but increased the oxidation to COz by uncoupling mitochondrial oxidative phosphorylation. Therefore, hyperammonemia and aspirin ingestion can inhibit fatty acid oxidation and mitochondrial metabolism that could lead to the pathophysiology seen in some childhood diseases such as Reye's syndrome. Carnitine therapy might offer some benefits. (Pediatr Res 25:119-123,1989 Abbreviations RS, Reye's syndrome ASP, acid soluble products V,, velocity calculated for saturating substrate (palmitic acid) concentration Elevation of serum-free fatty acids and fatty infiltration of liver are some of the common pathologic manifestations in children with enzyme defects of the urea cycle (1) and RS (2). Hyperammonemia is also an early laboratory finding in these disease states. It is suggested that the pathophysiology of RS is a metabolic response to an acute injury to mitochondria (3). Among many factors, salicylate, which is the predominant product circulating in blood after ingestion of aspirin, has been implicated in the etiology of RS (4). Salicylate may interfere with the synthesis of high energy phosphates and contribute to mitochondrial degeneration because salicylate uncouples mitochondrial respiration (5), inhibits the activation of fatty acids (6) and induces mitochondrial swelling (7). Similar damaging effec...

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Section: Discussionmentioning

confidence: 99%

Effects of Ammonium Chloride, Salicylate, and Carnitine on Palmitic Acid Oxidation in Rat Liver Slices

Maddaiah

Miller

1989

Pediatr Res

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Oxidative Metabolism

Urich¹

1994

Comparative Animal Biochemistry

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Mitochondrial enzymes and citrate transporter contribute to the aluminium-induced citrate secretion from soybean (Glycine max) roots

You

Ningning

et al. 2010

Functional Plant Biol.

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The concentration of soluble aluminium (Al) in the soil solution increases at low pH and the prevalence of toxic Al3+ cations represent the main factor limiting plant growth on acid soils. Citrate secretion from roots is an important Al-tolerance mechanism in many species including soybean. We isolated mitochondria from the roots of an Al-resistant soybean (Glycine max L.) cv. Jiyu 70 to investigate the relationship between citrate metabolism and Al-induced citrate secretion. Spectrophotometric assays revealed that the activities of mitochondrial malate dehydrogenase and citrate synthase increased and aconitase decreased with increasing of Al concentration (0–50 µM) and duration of Al treatment (30 µM Al, 0.5–9 h). Al-induced citrate secretion was inhibited by the citrate synthase inhibitor suramin, and enhanced by the aconitase inhibitor fluorocitric acid. Mersalyl acid, an inhibitor of a citrate carrier located in mitochondria membrane, also suppressed Al-induced citrate secretion. Transcript level of the mitochondrial citrate synthase gene increased in soybean roots exposed to Al, whereas expression of aconitase showed no significant difference. Expression of Gm-AlCT, a gene showing homology to Al-activated citrate transporters was also induced after 4 h in Al treatment. The Al-dependent changes in activity and expression of these enzymes are consistent with them supporting the sustained release of citrate from soybean roots.

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Citrate synthase from Crithidia fasciculata: Inhibition by adenine nucleotides and suramin

Cited by 4 publications

References 9 publications

Effects of Ammonium Chloride, Salicylate, and Carnitine on Palmitic Acid Oxidation in Rat Liver Slices

Effects of Ammonium Chloride, Salicylate, and Carnitine on Palmitic Acid Oxidation in Rat Liver Slices

Oxidative Metabolism

Mitochondrial enzymes and citrate transporter contribute to the aluminium-induced citrate secretion from soybean (Glycine max) roots

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