Fatty acid β-oxidation may occur in both mitochondria and peroxisomes. While peroxisomes oxidize specific carboxylic acids such as very long-chain fatty acids, branched-chain fatty acids, bile acids, and fatty dicarboxylic acids, mitochondria oxidize long-, medium-, and short-chain fatty acids. Oxidation of long-chain substrates requires the carnitine shuttle for mitochondrial access but medium-chain fatty acid oxidation is generally considered carnitine-independent. Using control and carnitine palmitoyltransferase 2 (CPT2)- and carnitine/acylcarnitine translocase (CACT)-deficient human fibroblasts, we investigated the oxidation of lauric acid (C12:0). Measurement of the acylcarnitine profile in the extracellular medium revealed significantly elevated levels of extracellular C10- and C12-carnitine in CPT2- and CACT-deficient fibroblasts. The accumulation of C12-carnitine indicates that lauric acid also uses the carnitine shuttle to access mitochondria. Moreover, the accumulation of extracellular C10-carnitine in CPT2- and CACT-deficient cells suggests an extramitochondrial pathway for the oxidation of lauric acid. Indeed, in the absence of peroxisomes C10-carnitine is not produced, proving that this intermediate is a product of peroxisomal β-oxidation. In conclusion, when the carnitine shuttle is impaired lauric acid is partly oxidized in peroxisomes. This peroxisomal oxidation could be a compensatory mechanism to metabolize straight medium- and long-chain fatty acids, especially in cases of mitochondrial fatty acid β-oxidation deficiency or overload.
Keywords: 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate; C12:0; CACT; CPT1; CPT2; Carnitine palmitoyltransferase 1; Carnitine palmitoyltransferase 2; Carnitine/acylcarnitine translocase; CrAT; CrOT; Fatty acid β-oxidation; LCFA; MCFA; Medium-chain fatty acids; Mitochondria; POCA; carnitine acetyltranferase; carnitine octanoyltransferase; carnitine palmitoyltranferase 1; carnitine palmitoyltransferase 2; carnitine/acylcarnitine translocase; l-AC; l-aminocarnitine; lauric acid; long-chain fatty acids; medium-chain fatty acids.
© 2013.