Peroxisomes contribute to the acylcarnitine production when the carnitine shuttle is deficient

Biochim Biophys Acta. 2013 Sep;1831(9):1467-74. doi: 10.1016/j.bbalip.2013.06.007. Epub 2013 Jul 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carnitine / analogs & derivatives*
  • Carnitine / metabolism*
  • Carnitine Acyltransferases / deficiency
  • Carnitine Acyltransferases / metabolism
  • Carnitine Acyltransferases / physiology*
  • Carnitine O-Palmitoyltransferase / physiology*
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Fluorescent Antibody Technique
  • Humans
  • Lauric Acids / chemistry
  • Lipid Metabolism, Inborn Errors / metabolism*
  • Lipid Metabolism, Inborn Errors / pathology
  • Oxidation-Reduction
  • Peroxisomes / metabolism*
  • Skin / cytology
  • Skin / metabolism*

Substances

  • Lauric Acids
  • acylcarnitine
  • lauric acid
  • Carnitine Acyltransferases
  • Carnitine O-Palmitoyltransferase
  • Carnitine

Supplementary concepts

  • Carnitine-Acylcarnitine Translocase Deficiency