Acetyl-L-carnitine as a precursor of acetylcholine.
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.
White
H L
HL
Division of Pharmacology, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
Scates
P W
PW
D000108:Acetylcarnitine / Q000378:metabolism*; D000109:Acetylcholine / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000201:enzymology; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003065:Coenzyme A / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000201:enzymology
D000108:Acetylcarnitine; D002795:Choline O-Acetyltransferase; D002332:Carnitine O-Acetyltransferase; D005947:Glucose; D000109:Acetylcholine; D003065:Coenzyme A