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Biochemistry. 1994 Nov 15;33(45):13259-66.

Role of sn-2 acyl group of phosphatidylcholine in determining the positional specificity of lecithin-cholesterol acyltransferase.

Author information

1
Department of Medicine, Rush Medical College, Chicago, Illinois 60612.

Abstract

Although human plasma lecithin-cholesterol acyltransferase (LCAT) is believed to be specific for the sn-2 position of phosphatidylcholine (PC), our recent studies showed that it derives a significant percent of acyl groups from the sn-1 position of certain PC species. To understand the physicochemical basis for this altered positional specificity, we determined the effect of sn-2 acyl group of PC on the enzyme activity and utilization of 16:0 from the sn-1 position by purified human and rat LCATs. Positional isomers of PC containing 16:0 at sn-2 were better substrates for human LCAT than the corresponding sn-1-16:0 isomers, whereas the reverse was true for rat LCAT. The positional specificity of human LCAT varied greatly depending on the nature of the acyl group at sn-2. The sn-1 contribution from various sn-1-16:0-2-acyl PCs for cholesteryl ester (CE) synthesis was 1.0% from 16:0-16:0, 1.4% from 16:0-20:5, 7.3% from 16:0-18:1, 47.0% from 16:0-20:3, 49.9% from 16:0-20:4, 54.9% from 16:0-22:6, and 72.3% from 16:0-18:0. There was a linear relationship between the percentage of 16:0 CE formed (from sn-1 position) and the acyl chain length at sn-2 position (r = 0.94). Rat LCAT also transferred some 16:0 from sn-1 position of 16:0-22:6, 16:0-20:3, and 16:0-18:0 PCs, but not from the other natural PCs tested. The phospholipase A activity of both LCATs in the presence of 16:0-20:4 PC showed the same positional specificity as CE synthesis, indicating that the specificity is determined at the formation of acyl-enzyme intermediate. These results show that the positional specificity of LCAT is influenced by the structure of PC, especially the chain length of the sn-2 acyl group.

PMID:
7947733
DOI:
10.1021/bi00249a012
[Indexed for MEDLINE]

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