Effect of apolipoprotein activators on the specificity of lecithin:cholesterol acyltransferase: determination of cholesteryl esters formed in A-I/C-III deficiency.
Although it is known that plasma lecithin:cholesterol acyltransferase (LCAT) is activated by several apolipoproteins (apo) including A-I, C-I, D, A-IV, and E, it is not clear what the physiological importance of having different apolipoprotein activators is. One possible explanation is that the activation by different apolipoproteins may result in the utilization of different species of phosphatidylcholine (PC), leading to the formation of different species of cholesteryl esters (CE). In order to determine this possibility, we analyzed the molecular species composition of PC and CE in two patients with familial deficiency of apoA-I and apoC-III. The LCAT activity, assayed by three different procedures, was found to be 36-63% of the control value. The lower LCAT activity, however, was due to deficiency of the enzyme rather than the absence of apoA-I. The patients' plasma was relatively enriched with sn-2 18:2 PC species reflecting the partial deficiency of LCAT activity. The fatty acid composition of plasma CE was not significantly different from that of controls. HPLC analysis of labeled CE formed after incubation of plasma with [C14]cholesterol showed no significant difference in the species of CE synthesized by the LCAT reaction. The transfer of pre-existing as well as newly formed CE from HDL to the apoB-containing lipoproteins was accelerated compared to control plasma. These results show that the absence of apoA-I does not significantly affect either the activity or the specificity of LCAT, and that the other apolipoprotein activators can substitute adequately for it.
Subbaiah
P V
PV
Department of Medicine, Rush Medical College, Chicago, IL 60612.
Norum
R A
RA
Bagdade
J D
JD
D000328:Adult; D016632:Apolipoprotein A-I / Q000172:deficiency*; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000172:deficiency*; D002788:Cholesterol Esters / Q000097:blood*; D005260:Female; D006801:Humans; D007700:Kinetics; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood*; D010713:Phosphatidylcholines / Q000097:blood*; D013379:Substrate Specificity
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D002788:Cholesterol Esters; D010713:Phosphatidylcholines; D007862:Phosphatidylcholine-Sterol O-Acyltransferase