Molecular enzymology of carnitine transfer and transport

Carnitine (L-3-hydroxy-4-N-trimethylaminobutyric acid) forms esters with a wide range of acyl groups and functions to transport and excrete these grou ps. It is found in most cells at millimolar levels after uptake via the sod ium-dependent carrier, OCTN2. The acylation state of the mobile carnitine p ool is linked to that of the limited and compartmentalised coenzyme A pools by the action of the family of carnitine acyltransferases and the mitochon drial membrane transporter, CACT. The genes and sequences of the carriers a nd the acyltransferases are reviewed along with mutations that affect activ ity. After summarising the accepted enzymatic background, recent molecular studies on the carnitine acyltransferases are described to provide a pictur e of the role and function of these freely reversible enzymes. The kinetic and chemical mechanisms are also discussed in relation to the different inh ibitors under study for their potential to control diseases of lipid metabo lism. (C) 2001 Elsevier Science B.V. All rights reserved.