In this pathway, referred to as the carnitine shuttle, long-chain fatty acyl-CoAs (such as palmitoyl-CoA, produced by long-chain-fatty-acid-CoA ligase 1, EC 6.2.1.3) are trans-esterified to L-carnitine by carnitine palmitoyltransferase 1a (one of three possible tissue isoforms) at the mitochondrial outer membrane. Genes encoding mammalian liver, muscle and brain isoforms of this enzyme have been identified as Cpt1a, Cpt1b and Cpt1c, respectively. This rate-limiting enzyme is a key regulatory step for fatty acid β-oxidation due to its sensitivity to inhibition by malonyl-CoA produced during fatty acid biosynthesis (see pathway fatty acid biosynthesis initiation I). It is also of interest as a target for anti-obesity and anti-diabetes drugs . A specific carrier, the carnitine-acylcarnitine translocase, then transports the long-chain O-acyl-L-carnitine esters through the inner mitochondrial membrane. Reviewed in.