Not only CPT and CPT but also carnitine
Not only CPT1 and CPT2, but also carnitine octanoyltransferase (CrOT) transesterifies medium- and long-chain acyl-CoAs, although this enzyme is located in peroxisomes rather than mitochondria. Its function is to enable the transport of octanoyl-CoA derived from the ω-oxidation of very-long-chain and branched-chain fatty acids [1,18,19]. Octanoylcarnitine is able to be shuttled into mitochondria for further oxidation. Carnitine acetyltransferase (CrAT) transesterifies short-chain acyl-CoAs, and is located both in mitochondria and peroxisomes. In yeasts and mammals this protein is the product of a single gene [20,21] and the sorting to different organelles is evolutionary conserved, although the mechanism of differential sorting is quite different [, , ] (reviewed by van der Leij et al. ). The yeast Sc-CrAT is expressed by Sc-CAT2 (Fig. 1) . However, two more genes responsible for acetyltransferase activity have been described [25,26]. These transferases, Sc-YAT1 and Sc-YAT2, are located in the cytosol (Fig. 1). Apart from these three acetyltransferases, of which orthologues exist in other fungi, no other fungal carnitine or choline acyltransferases have been described. Finally, choline acetyltransferase (ChAT) is located in the nucleus and cytoplasm of cholinergic neurons of the central and peripheral nervous systems [27,28]. This is the only transferase within this family that transfers acetyl-CoAs to choline instead of carnitine, which results in the formation of the neurotransmitter ABT 702 dihydrochloride (the function of acetylcholine in the central nervous system is reviewed by Oda et al. ). Cholinergic neurons are involved in the regulation of memory, learning, motor function and in the control of several visceral functions [, , ]. Low ChAT activity has been associated with a number of neurodegenerative diseases . Two isoforms of ChAT exist. Next to the common form of ChAT (cChAT), a second isoform has been discovered (pChAT), which is mainly expressed in the peripheral nerve tissue . In the cell, cChAT is mainly present in the cytosol, but can also bind to the plasma membrane and localize to the nucleus, whereas pChAT is only present in the cytosol . Both isoforms are encoded by the same sequence, but the isoform cChAT (640 amino acids) results from conventional splicing, whereas pChAT (430 amino acids) results from alternative splicing by exon skipping (exon 6–9). In mammals, the nine amino acid residues necessary for binding choline and acetyl-CoA are present in both isoforms, but in pChAT the amino acid residue histidine involved in the catalytic centre is lost during exon skipping [33,34]. However, both isoforms have ChAT activity, that of pChAT being lower than cChAT . Since acetylcholine is also involved in non-neuronal functions , it needs to be clarified whether and to what extend pChAT is involved in cholinergic neurotransmission. The expression of pChAT is conserved during evolution, since it is widely spread among invertebrate and vertebrate phyla [33,34,36]. This stresses the importance of the cholinergic system in peripheral tissues.