Acetyl-l-carnitine as a precursor of acetylcholine

Abstract

Synthesis of [3H]acetylcholine from [3H]acetyl-L-carnitine was demonstrated in vitro by coupling the enzyme systems choline acetyltransferase and carnitine acetyltransferase. Likewise, both [3H] and [14C] labeled acetylcholine were produced when [3H]acetyl-L-carnitine and D-[U-14C] glucose were incubated with synaptosomal membrane preparations from rat brain. Transfer of the acetyl moiety from acetyl-L-carnitine to acetylcholine was dependent on concentration of acetyl-L-carnitine and required the presence of coenzyme A, which is normally produced as an inhibitory product of choline acetyltransferase. These results provide further evidence for a role of mitochondrial carnitine acetyltransferase in facilitating transfer of acetyl groups across mitochondrial membranes, thus regulating the availability in the cytoplasm of acetyl-CoA, a substrate of choline acetyltransferase. They are also consistent with a possible utility of acetyl-L-carnitine in the treatment of age-related cholinergic deficits.

Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl- l -carnitine and/or R -α-lipoic acid

“…The cognition-improving effect of ALCAR may also be caused in part by the donation of an acetyl group for the synthesis of the neurotransmitter acetylcholine through choline acetyltransferase and carnitine acetyltransferase (17,71,72). Low acetylcholine levels in certain brain regions are associated with age-related cognitive dysfunction, including AD (73).…”

Cytoprotective Effect of Acetyl-l-Carnitine Evidenced by Analysis of Gene Expression in the Rat Brain

“…ALC is involved in cognitive functions and neuronal bioenergetics mechanisms with both short-and long-term treatments in rats [14], and there is some experimental evidence that ALC might also have antiaging effects and cardioprotective activity [11,15,16], restoring the age-associated decline of learning and memory in old animals [17]. Several studies have also indicated that ALC potentiates the cholinergic transmission and provides a possible tool for Alzheimer's disease (AD) treatment [18]. A recent study suggests that supplementation with ALC improves spatial working memory deficits, reduces oxidative stress, and inhibits apoptotic cascade induced by hypoxia [19].…”

Primary L-carnitine deficiencies – symptoms, clinical syndromes, proceed ings

“…L-karnityna uczestniczy również w przekształcaniu acetylo-koenzymu A (acetylo-CoA) do acetylokarnityny i koenzymu A (CoA), co w efekcie zwiększa dostępność CoA potrzebnego do dekarboksylacji oksydacyjnej pirogronianu w cyklu Krebsa. W układzie nerwowym acetylokarnityna jest donorem grup acetylowych niezbędnych do tworzenia acetylocholiny [17,18]. Poza rolą w utlenianiu kwasów tłuszczowych L-karnityna bierze udział w metabolizmie aminokwasów (leucyny, izoleucyny i waliny) oraz w chelatowaniu takich pierwiastków jak żelazo, ołów i kadm, ułatwiając ich transport oraz usuwanie ich nadmiaru [1].…”