Significance of l-carnitine for human health

IUBMB Life. 2017 Aug;69(8):578-594. doi: 10.1002/iub.1646. Epub 2017 Jun 26.

Abstract

Carnitine acyltransferases catalyze the reversible transfer of acyl groups from acyl-coenzyme A esters to l-carnitine, forming acyl-carnitine esters that may be transported across cell membranes. l-Carnitine is a wáter-soluble compound that humans may obtain both by food ingestion and endogenous synthesis from trimethyl-lysine. Most l-carnitine is intracellular, being present predominantly in liver, skeletal muscle, heart and kidney. The organic cation transporter-2 facilitates l-carnitine uptake inside cells. Congenital dysfunction of this transporter causes primary l-carnitine deficiency. Carnitine acetyltransferase is involved in the export of excess acetyl groups from the mitochondria and in acetylation reactions that regulate gene transcription and enzyme activity. Carnitine octanoyltransferase is a peroxysomal enzyme required for the complete oxidation of very long-chain fatty acids and phytanic acid, a branched-chain fatty acid. Carnitine palmitoyltransferase-1 is a transmembrane protein located on the outer mitochondrial membrane where it catalyzes the conversion of acyl-coenzyme A esters to acyl-carnitine esters. Carnitine acyl-carnitine translocase transports acyl-carnitine esters across the inner mitochondrial membrane in exchange for free l-carnitine that exits the mitochondrial matrix. Carnitine palmitoyltransferase-2 is anchored on the matrix side of the inner mitochondrial membrane, where it converts acyl-carnitine esters back to acyl-coenzyme A esters, which may be used in metabolic pathways, such as mitochondrial β-oxidation. l-Carnitine enhances nonoxidative glucose disposal under euglycemic hyperinsulinemic conditions in both healthy individuals and patients with type 2 diabetes, suggesting that l-carnitine strengthens insulin effect on glycogen storage. The plasma level of acyl-carnitine esters, primarily acetyl-carnitine, increases during diabetic ketoacidosis, fasting, and physical activity, particularly high-intensity exercise. Plasma concentration of free l-carnitine decreases simultaneously under these conditions. © 2017 IUBMB Life, 69(8):578-594, 2017.

Keywords: acetyl-coA; carnitine acetyltransferase; carnitine octanoyltransferase; carnitine palmitoyltransfer; organic cation transporter-2.

Publication types

  • Review

MeSH terms

  • Cardiomyopathies / genetics*
  • Cardiomyopathies / metabolism
  • Carnitine / deficiency*
  • Carnitine / genetics
  • Carnitine / metabolism*
  • Carnitine Acyltransferases / genetics
  • Fatty Acids / metabolism
  • Humans
  • Hyperammonemia / genetics*
  • Hyperammonemia / metabolism
  • Liver / enzymology*
  • Liver / metabolism
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Muscular Diseases / genetics*
  • Muscular Diseases / metabolism
  • Oxidation-Reduction
  • Solute Carrier Family 22 Member 5 / genetics*
  • Solute Carrier Family 22 Member 5 / metabolism

Substances

  • Fatty Acids
  • Solute Carrier Family 22 Member 5
  • Carnitine Acyltransferases
  • Carnitine

Supplementary concepts

  • Systemic carnitine deficiency