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Figure 1. L -Acetylcarnitine provides acetyl groups for acetylcholine synthesis. CAT: Carnitine acetyltransferase; ChAT: Choline acetyltransferase; ACh: Acetylcholine
(Figure omitted. See article PDF.)
Figure 2. LAC enhances the transcription of the GRM2 gene encoding the mGlu2 receptor by acting as a donor of acetyl groups to NF-κB p65/RelA.
(Figure omitted. See article PDF.)
History
Discovery
Carnitine was isolated from the bovine muscle in 1905 by W. Gulewitsch and R. Krimberg in the laboratories of the University of Moscow, and by F. Kutscher in Marburg. However, its chemical structure was only defined 22 years later [1] when Fraenkel described the growth factor of the larvae of Tenebrio molitor , and named it vitamin BT, unaware that it was carnitine itself [1-4].
The physiological role of carnitine remained unknown until 1955, when Irving Fritz from the University of Michigan showed that it stimulated the oxidation of fatty acids [5]. Its role was eventually clarified in 1962, when Bremer et al . showed it was involved in the transport of fatty acids across the mitochondrial membranes, where lipids and glucose are oxidized, producing energy [6-9]. The oxidation of glucose and fatty acids leads to the formation of acetate linked to co-enzyme A, that is, acetyl CoA. CoA is a carrier of molecules formed during the oxidation of glucose and lipids; unavailability of CoA blocks the transfer of oxidative products. The amount of CoA is fixed within the mitochondria; instead, any increase in the oxidative processes may lead to an excess of acetate. The excess of acetate consequently will bind all the available CoA.
Once it has entered the mitochondria to transport the fatty acids, carnitine joins acetyl CoA, becoming acetylcarnitine. This reaction de-acetylates CoA and enables the system to restart the oxidative products transport cycle [10]. Acetylcarnitine finally leaves the mitochondria through the carnitine acyl carnitine translocase enzyme [11], which carries carnitine linked to fatty acids inside the mitochondria and carries outside free carnitine or ALC [10,11].
In 1936, Weger studied the vagal effects of ALC on the isolated frog heart by blocking them with atropine. The following year, Strack found that ALC isolated from different somatic and visceral muscles of the frog, rabbit and mouse had a less powerful cholinergic effect than acetylcholine, and this effect...