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- -lipoic acid

Extrapolation from in vitro to in vivo results should be viewed with caution, we suggest two plausible mechanisms that could account for the age-associated loss of binding affinity and activity: adduction to the protein of aldehyde products of lipid peroxidation, or oxidation of the protein either directly by oxidants or by metal-catalyzed oxidation

J. Liu; D. W. Killilea; B. N. Ames

2002

Scholarcy highlights

  • Aging appears to be due, in part, to damage caused by the oxidants produced by mitochondria as by-products of normal metabolism
  • Feeding old rats ALCAR for 7 weeks, which elevates the level of free and acyl carnitines in blood and brain to a level of about 100 ␮M, significantly restored this age-associated decrease in binding affinity for ALCAR; the combination of ALCAR and lipoic acid significantly restored both carnitine acetyltransferase activity and its binding affinity for the substrates ALCAR and CoA to the levels observed in young rats
  • Feeding old rats LA significantly enhanced the effect of ALCAR, LA alone had only a small effect on CAT activity and substrate-binding affinity
  • Extrapolation from in vitro to in vivo results should be viewed with caution, we suggest two plausible mechanisms that could account for the age-associated loss of binding affinity and activity: adduction to the protein of aldehyde products of lipid peroxidation, or oxidation of the protein either directly by oxidants or by metal-catalyzed oxidation
  • We show that MDA and HNE, another lipid peroxidation product, decrease the Vmax and binding affinity of CAT in vitro, whereas a direct oxidant, i.e., iron, does not
  • MDA and HNE are only two of the many known active aldehydes formed from lipid peroxidation, many of which may contribute to enzyme inactivation
  • Ex vivo oxidation of young-rat brain with Fe(II) induced similar reduction of enzyme activity and binding affinity; in vitro oxidation of purified carnitine acetyltransferase with Fe(II) inactivated the enzyme but did not

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