Free and esterified coenzyme A in the liver and muscles of chronically hyperammonemic mice treated with sodium benzoate.

Abstract

Ammonia toxicity and relative sodium benzoate toxicity alters the energy metabolism, leading to a decrease of adenosine triphosphate and free coenzyme A levels. The object of the present study was to analyze the hepatic and muscular acyl-coenzyme A profiles in chronically hyperammonemic mice treated with varying doses of the sodium benzoate. An enzymatic method was used for the measurement of free coenzyme A, acetyl-coenzyme A, and medium and long chain acyl-coenzyme A. Untreated chronic hyperammonemia resulted in a decrease in acetyl-coenzyme A and an increase in the long chain acyl-coenzyme A in the liver, accompanied by an increase in total coenzyme A in the muscular tissues. Treatment with sodium benzoate at moderate doses, caused a decrease in the hepatic free and esterified coenzyme A while these were increased at higher doses. We conclude that chronic hyperammonemia is responsible for qualitative changes in the free and esterified coenzyme A profile in the liver, while causing qualitative and quantitative changes in the muscular tissue, probably due to an inhibition of mitochondrial oxidation. The sodium benzoate had a biphasic effect on the hepatic content of free and esterified coenzyme A, suggesting a degradation of coenzyme A at moderate doses. However, at a higher dose of benzoate, the possibility of glycine mobilization and/or a significant formation of acylcarnitines is proposed as an important factor in an increase of the hepatic total coenzyme A.

• Authors: A Michalak, I A Qureshi
• Journal: Biochemical and molecular medicine (Biochem Mol Med) Vol. 54 Issue 2 Pg. 96-104 (Apr 1995) ISSN: 1077-3150 [Print] United States
• PMID: 8581365 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzoates
• Food Preservatives
• Acetyl Coenzyme A
• Ammonia
• Benzoic Acid
• Coenzyme A

Topics

• Acetyl Coenzyme A (chemistry, drug effects, metabolism)
• Ammonia (blood)
• Animals
• Benzoates (pharmacology)
• Benzoic Acid
• Chronic Disease
• Coenzyme A (chemistry, drug effects, metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Food Preservatives
• Liver (chemistry, drug effects)
• Male
• Mice
• Mice, Inbred ICR
• Muscle, Skeletal (chemistry, drug effects)
• Ornithine Carbamoyltransferase Deficiency Disease