THE MITOCHONDRIAL CARNITINE PALMITOYLTRANSFERASE SYSTEM - FROM CONCEPT TO MOLECULAR ANALYSIS

First conceptualized as a mechanism for the mitochondrial transport of long-chain fatty acids in the early 1960s, the carnitine palmitoyltra nsferase (CPT) system has since come to be recognized as a pivotal com ponent of fuel homeostasis. This is by virtue of the unique sensitivit y of the outer membrane CPT I to the simple molecule, malonyl-CoA. In addition, both CPT I and the inner membrane enzyme, CPT II, have prove d to be loci of inherited defects, some with disastrous consequences. Early efforts using classi cal approaches to characterize the CPT prot eins in terms of structure/function/regulatory relationships gave rise to confusion and protracted debate. By contrast, recent application o f molecular biological tools has brought major enlightenment at an exp onential pace. Here we review some key developments of the last 20 yea rs that have led to our current understanding of the physiology of the CPT system, the structure of the CPT isoforms, the chromosomal locali zation of their respective genes, and the identification of mutations in the human population.