Carnitine metabolic actions

Pettigrew JW, Levine J and McClure RJ (2000). Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties Relevance for its mode of action in Alzheimer s disease and geriatric depression. Molecular Psychiatry, 5, 626-632. 

Mechanism of Action Assists in collagen formation and tissue repair and is involved in oxidation reduction reactions and other metabolicreactions.TAerapeMficEffect Involved in carbohydrate use and metabolism, as well as synthesis of carnitine, lipids, and proteins. Preserves blood vessel integrity. 

Under physiologic conditions, carnitine is primarily required to shuttle long-chain fatty acids across the inner mitochondrial membrane for FAO and products of peroxisomal /1-oxidation to the mitochondria for further metabolism in the citric acid cycle [40, 43]. Acylcarnitines are formed by conjugating acyl-CoA moieties to carnitine, which in the case of activated long-chain fatty acids is accomplished by CPT type I (CPT-I) [8, 44]. The acyl-group of the activated fatty acid (fatty acyl-CoA) is transferred by CPT-I from the sulfur atom of CoA to the hydroxyl group of carnitine (Fig. 3.2.1). Carnitine acylcarnitine translocase (CACT) then transfers the long-chain acylcarnitines across the inner mitochondrial membrane, where CPT-II reverses the action of CPT-I by the formation of acyl-CoA and release of free un-esterified carnitine. 

Orally administered L-carnitine and propionyl-L-carnitine may have metabolic benefits by providing an additional source of carnitine to buffer the cellular acyl CoA pool. In this way, carnitine may enhance glucose oxidation under ischemic conditions and improve energy metabolism in the ischemic skeletal muscle. Propionyl-CoA generated from propionyl-L-carnitine may also improve oxidative metabolism through its anaphoretic actions in priming the Kreb s cycle, secondary to succinyl-CoA production. 

A. Valproic acid is a low-molecular-weight (144.21), branched-chain carboxylic acid (pKg = 4.8) that increases levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and prolongs the recovery of inactivated sodium channels. These properties may be responsible tor its action as a general central nervous system depressant. Valproic acid also alters amino acid and fatty acid metabolism with dismption of the urea cycle, and can cause hepatotoxicity, metabolic perturbations, cerebral edema, and bone marrow depression. Some of these effects may be associated with carnitine deficiency. 

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