Cloning and expression of a novel lysophospholipase which structurally resembles lecithin cholesterol acyltransferase

Lecithin cholesterol acyltransferase (LCAT) is the key enzyme in the esteri fication of plasma cholesterol and in the reverse cholesterol transport on high-density lipoprotein (HDL). We have found a novel LCAT-related gene amo ng differentially expressed cDNA fragments between two types of foam cells derived from THP-I cells, which are different in cholesterol efflux ability , using a subtractive PCR technique. The deduced 412-amino-acid sequence ha s 49% amino acid sequence similarity with human LCAT. in contrast to the Li ver-specific expression of LCAT, mRNA expression of the gene was observed m ainly in peripheral tissues including kidney, placenta, pancreas, testis, s pleen, heart, and skeletal muscle. The protein exists in human plasma and i s probably associated with HDL. Moreover, we discovered that the recombinan t protein hydrolyzed lysophosphatidylcholine (lysoPC), a proatherogenic lip id, to glycerophosphorylcholine and a free fatty acid. We have therefore na med this novel enzyme LCAT-like lysophospholipase (LLPL), through which a n ew catabolic pathway for lysoPC on lipoproteins could be elucidated. (C) 19 99 Academic Press.