Taniyama Y, Shibata S, Kita S, Horikoshi K, Fuse H, Shirafuji H, Sumino Y, Fujino M
Pharmaceutical Discovery Research Division, Takeda Chemical Industries Ltd., 10 Wadai, Tsukuba, Ibaraki, 300-4293, Japan.
Biochem Biophys Res Commun. 1999 Apr 2;257(1):50-6. doi: 10.1006/bbrc.1999.0411.
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.
卵磷脂胆固醇酰基转移酶（LCAT）是血浆胆固醇酯化以及高密度脂蛋白（HDL）上胆固醇逆向转运过程中的关键酶。我们使用消减PCR技术，在源自THP - 1细胞的两种胆固醇流出能力不同的泡沫细胞之间的差异表达cDNA片段中，发现了一个新的与LCAT相关的基因。推导的412个氨基酸的序列与人类LCAT具有49%的氨基酸序列相似性。与LCAT的肝脏特异性表达不同，该基因的mRNA表达主要在包括肾脏、胎盘、胰腺、睾丸、脾脏、心脏和骨骼肌在内的外周组织中观察到。该蛋白存在于人体血浆中，可能与HDL相关。此外，我们发现重组蛋白将促动脉粥样硬化脂质溶血磷脂酰胆碱（lysoPC）水解为甘油磷酸胆碱和游离脂肪酸。因此，我们将这种新酶命名为LCAT样溶血磷脂酶（LLPL），通过它可以阐明脂蛋白上lysoPC的一条新的分解代谢途径。
