Age-associated mitochondrial oxidative decay: Improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl- l - carnitine and/or R -α-lipoic acid

• DOI: 10.1073/pnas.261709098
• Publication Date: 2002-07-26T14:36:44Z
• Authors: Jiankang Liu; David W. Killilea; Bruce N. Ames
• Keywords: Malondialdehyde

We test whether the dysfunction with age of carnitine acetyltransferase (CAT), a key mitochondrial enzyme for fuel utilization, is due to decreased binding affinity substrate and this substrate, fed old rats, restores CAT activity. The kinetics were analyzed by using brains young rats supplemented 7 weeks acetyl- l -carnitine (ALCAR) and/or antioxidant precursor R -α-lipoic acid (LA). Old compared showed decrease in activity CAT-binding both substrates, ALCAR CoA. Feeding or plus LA significantly restored CoA, To explore underlying mechanism, lipid peroxidation total iron copper levels assayed; all increased rats. inhibited but did not levels. Ex vivo oxidation young-rat brain Fe(II) caused loss affinity. In vitro purified inactivated alter However, treatment products malondialdehyde 4-hydroxy-nonenal activity, thus mimicking age-related change. Preincubation CoA prevented malondialdehyde-induced dysfunction. Thus, feeding high metabolites can ameliorate oxidative damage, substrate-binding affinity,