Free and esterified coenzyme A in the liver and muscles of chronically hyperammonemic mice treated with sodium benzoate.
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.
Michalak
A
A
Research Center, Ste-Justine Hospital 3175, Montréal, Québec Canada.
Qureshi
I A
IA
D000105:Acetyl Coenzyme A / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000641:Ammonia / Q000097:blood*; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D019817:Benzoic Acid; D002908:Chronic Disease; D003065:Coenzyme A / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005520:Food Preservatives; D008099:Liver / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000187:drug effects; D020163:Ornithine Carbamoyltransferase Deficiency Disease
D001565:Benzoates; D005520:Food Preservatives; D000105:Acetyl Coenzyme A; D000641:Ammonia; D019817:Benzoic Acid; D003065:Coenzyme A