Sodium benzoate inhibits fatty acid oxidation in rat liver: effect on ammonia levels.
Sodium benzoate inhibited PC and octanoic acid-mediated State 3 respiration rates by 39 and 29%, respectively, at 0.5 mM in isolated rat liver mitochondria. At 2 mM, benzoate did not affect State 3 respiration rates with either succinate or malate plus glutamate, indicating that it did not act as an uncoupler. The oxidation of palmitate and octanoate was inhibited by 39 and 54% at 2 mM benzoate in liver homogenates. Benzoate, at 10 mmol/kg caused significant decreases in the levels of hepatic ATP, CoA, and acetyl-CoA. Administration of sodium benzoate to rats caused a dose-dependent increase in hepatic ammonia levels. However, the inhibitory effect of benzoate on fatty acid oxidation is not mediated through ammonia since ammonium chloride, at 1 mM, did not inhibit PC or octanoate oxidation in mitochondria or their oxidation in liver homogenate. Our results warrant a reevaluation of the use of sodium benzoate in the treatment of hyperammonemia.
Kalbag
S S
SS
Department of Pediatrics, Nassau County Medical Center, New York.
Palekar
A G
AG
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D019817:Benzoic Acid; D002210:Caprylates / Q000378:metabolism; D003065:Coenzyme A / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001565:Benzoates; D002210:Caprylates; D005227:Fatty Acids; D010168:Palmitates; D000105:Acetyl Coenzyme A; D000641:Ammonia; D000255:Adenosine Triphosphate; D019817:Benzoic Acid; D003065:Coenzyme A