Cloning and expression of a novel lysophospholipase which structurally resembles lecithin cholesterol acyltransferase.
Lecithin cholesterol acyltransferase (LCAT) is the key enzyme in the esterification of plasma cholesterol and in the reverse cholesterol transport on high-density lipoprotein (HDL). We have found a novel LCAT-related gene among differentially expressed cDNA fragments between two types of foam cells derived from THP-1 cells, which are different in cholesterol efflux ability, using a subtractive PCR technique. The deduced 412-amino-acid sequence has 49% amino acid sequence similarity with human LCAT. In contrast to the liver-specific expression of LCAT, mRNA expression of the gene was observed mainly in peripheral tissues including kidney, placenta, pancreas, testis, spleen, heart, and skeletal muscle. The protein exists in human plasma and is probably associated with HDL. Moreover, we discovered that the recombinant protein hydrolyzed lysophosphatidylcholine (lysoPC), a proatherogenic lipid, to glycerophosphorylcholine and a free fatty acid. We have therefore named this novel enzyme LCAT-like lysophospholipase (LLPL), through which a new catabolic pathway for lysoPC on lipoproteins could be elucidated.
Taniyama
Y
Y
Pharmaceutical Discovery Research Division, Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki, 300-4293, Japan. Taniyama_Yoshio@takeda.co.jp
Shibata
S
S
Kita
S
S
Horikoshi
K
K
Fuse
H
H
Shirafuji
H
H
Sumino
Y
Y
Fujino
M
M
D000595:Amino Acid Sequence; D016367:Baculoviridae / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002087:Butyrates / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D005487:Foam Cells / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008245:Lysophospholipase / Q000097:blood / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000737:chemistry* / Q000235:genetics; D010713:Phosphatidylcholines / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D002087:Butyrates; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D007531:Isoflurophate; C033592:4-nitrophenyl butyrate; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D008245:Lysophospholipase; C017251:1,2-oleoylphosphatidylcholine