2002
DOI: 10.1073/pnas.261709098
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Abstract: We test whether the dysfunction with age of carnitine acetyltransferase (CAT), a key mitochondrial enzyme for fuel utilization, is due to decreased binding affinity for substrate and whether this substrate, fed to old rats, restores CAT activity. The kinetics of CAT were analyzed by using the brains of young and old rats and of old rats supplemented for 7 weeks with the CAT substrate acetyl-Lcarnitine (ALCAR) and͞or the mitochondrial antioxidant precursor R-␣-lipoic acid (LA). Old rats, compared with young rat… Show more

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Cited by 243 publications
(192 citation statements)
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“…Additionally, acetyl L-carnitine attenuated ketamine-induced behavioral alterations and body weight decrements in preweaning rats (Boctor et al, 2008) and was found to exert efficient preventive effects in a cellular model of Parkinson's disease (Zhang et al, 2010). Beneficial effects of acetyl L-carnitine on cognitive and mitochondrial dysfunction have been shown in aging rats (Hagen et al, 2002a;Liu et al, 2002), as well. In our earlier study, we speculated that acetyl L-carnitine's reversal of ketamine-induced decrease in heart rate and ERK/MAPK activity could be mediated by calcium-modulated signaling (Kanungo et al, 2012).…”
Section: Discussionmentioning
confidence: 96%
“…Additionally, acetyl L-carnitine attenuated ketamine-induced behavioral alterations and body weight decrements in preweaning rats (Boctor et al, 2008) and was found to exert efficient preventive effects in a cellular model of Parkinson's disease (Zhang et al, 2010). Beneficial effects of acetyl L-carnitine on cognitive and mitochondrial dysfunction have been shown in aging rats (Hagen et al, 2002a;Liu et al, 2002), as well. In our earlier study, we speculated that acetyl L-carnitine's reversal of ketamine-induced decrease in heart rate and ERK/MAPK activity could be mediated by calcium-modulated signaling (Kanungo et al, 2012).…”
Section: Discussionmentioning
confidence: 96%
“…The complementary effect of LA and ALC on cognitive and mitochondrial dysfunction has been shown in ageing rats [27,28,40]. One reason is that LA+ALC act on different pathways necessary for mitochondria: LA is a mitochondrial antioxidant and cofactor of pyruvate dehydrogenase, while ALC is an energy enhancer [25,41].…”
Section: Discussionmentioning
confidence: 99%
“…ALC is the acetyl derivative of L-carnitine, which is required for the transport of long-chain fatty acids into the mitochondria for β-oxidation, ATP production and for the removal of excess short-and medium-chain fatty acids [25]. LA and/or ALC improve mitochondrial function in ageing rats and their combination appears more potent owing to complementary effects [25][26][27][28]. LA [29] and ALC [30,31] have been tested in several large clinical trials on prevention or treatment of diabetes and its complications.…”
Section: Introductionmentioning
confidence: 99%
“…Under conditions of metabolic stress, mitochondria accumulate acyl-coenzyme A (acyl-CoA), which can inhibit oxidative phosphorylation (12). There is a decline in mitochondrial function associated with aging (30,31), and oxidative damage to the mitochondrial enzymes regulating carnitine homeostasis is an important mediator in this process (30,31). The principal enzyme affected has been identified as carnitine acetyltransferase (CrAT), which catalyzes a reversible equilibrium reaction between acyl-CoA and CoA, and acylcarnitine and carnitine (59).…”
mentioning
confidence: 99%