Acetyl-L-carnitine Supplementation Reverses the Age-related Decline in Carnitine Palmitoyltransferase 1 (CPT1) Activity in Interfibrillar Mitochondria Without Changing the L-carnitine Content in the Rat Heart

Overview

Journal Mech Ageing Dev

Specialty Geriatrics

Date 2012 Feb 11

PMID 22322067

Citations 15

Authors

Luis A Gomez

Shi-Hua D Heath

Tory M Hagen

Affiliations

Soon will be listed here.

Abstract

The aging heart displays a loss of bioenergetic reserve capacity partially mediated through lower fatty acid utilization. We investigated whether the age-related impairment of cardiac fatty acid catabolism occurs, at least partially, through diminished levels of L-carnitine, which would adversely affect carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme for fatty acyl-CoA uptake into mitochondria for β-oxidation. Old (24-28 mos) Fischer 344 rats were fed±acetyl-L-carnitine (ALCAR; 1.5% [w/v]) for up to four weeks prior to sacrifice and isolation of cardiac interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria. IFM displayed a 28% (p<0.05) age-related loss of CPT1 activity, which correlated with a decline (41%, p<0.05) in palmitoyl-CoA-driven state 3 respiration. Interestingly, SSM had preserved enzyme function and efficiently utilized palmitate. Analysis of IFM CPT1 kinetics showed both diminished V(max) and K(m) (60% and 49% respectively, p<0.05) when palmitoyl-CoA was the substrate. However, no age-related changes in enzyme kinetics were evident with respect to L-carnitine. ALCAR supplementation restored CPT1 activity in heart IFM, but not apparently through remediation of L-carnitine levels. Rather, ALCAR influenced enzyme activity over time, potentially by modulating conditions in the aging heart that ultimately affect palmitoyl-CoA binding and CPT1 kinetics.

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