Authors
Zempleni J. Trusty TA. Mock DM.
Institution
Department of Pediatrics, University of Arkansas for Medical Sciences and the
Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
Title
Lipoic acid reduces the activities of
biotin-dependent carboxylases in rat liver.
Source
Journal of Nutrition. 127(9):1776-81, 1997 Sep.
Abstract
In the past, lipoic acid has been administered to patients
and test animals as therapy for diabetic neuropathy and various
intoxications. Lipoic acid and the vitamin
biotin have structural similarities. We sought to determine
whether the chronic administration of lipoic acid affects
the activities of biotin-dependent carboxylases. For 28 d,
rats received daily intraperitoneal injections of one of the following: 1) a
small dose of lipoic acid [4.3 micromol/( kg.d)]; 2) a large
dose of lipoic acid [15.6 micromol/(kg.d)]; or 3) a large
dose of lipoic acid plus biotin [15.6 and
2.0 micromol/(kg.d), respectively]. Another group received n-hexanoic
acid [14.5 micromol/(kg.d)], which has structural
similarities to lipoic acid and biotin and
thus served as a control for the specificity of lipoic acid.
A fifth group received phosphatidylcholine in saline injections and served as
the vehicle control. The rat livers were assayed for the activities of
acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and
beta-methylcrotonyl-CoA carboxylase. Urine was analyzed for lipoic
acid; serum was analyzed for indicators of liver damage and
metabolic aberrations. The mean activities of pyruvate carboxylase and
beta-methylcrotonyl-CoA carboxylase were 28-36% lower in the lipoic
acid-treated rats compared with vehicle controls (P < 0.05).
Rats treated with lipoic acid plus biotin
had normal carboxylase activities. Carboxylase activities in livers of
n-hexanoic acid-treated rats were normal despite some
evidence of liver injury. Propionyl-CoA carboxylase and acetyl-CoA
carboxylase were not significantly affected by administration of lipoic
acid. This study provides evidence consistent with the
hypothesis that chronic administration of lipoic acid lowers
the activities of pyruvate carboxylase and beta-methylcrotonyl-CoA
carboxylase in vivo by competing with biotin.
Additional note by poster:
High dose lipoic acid is less effective than low dose in the treatment of diabetic neuropathy. This may be due to an induced marginal biotin deficiency. Megadose biotin itself has been found to be significantly more effective than lipoic acid in treatment of diabetics.