Apolipoproteins: Significance and measurement

Abstract

Plasma lipoproteins are particles containing lipid (cholesterol, cholesteryl ester, triglyceride, phospholipid) and specific proteins (apoproteins). Lipoproteins are generally classified by density. This is a useful operational classification and also one which bears some relationship to function, in that the less dense lipoproteins (chylomicrons), very low density lipoprotein (VLDL), low density lipoprotein (LDL) transport lipid from intestine or liver, whereas high density lipoproteins (HDL), it is thought, play a part in the passage of cholesterol from extrahepatic cells to the liver. The apoproteins serve a number of functions, but the function of many is unknown. Known functions include: a. Structural functions. ApoB is an essential protein for the formation of chylomicrons, VLDL and LDL. ApoA appears essential for HDL formation. b. Coenzyme activity. ApoCTI is a coenzyme for lipoprotein lipase, and apoAI for leeithin:cholesterol acyltransferase ( LCAT). c. Markers, allowing uptake and catabolism of specific lipoproteins. ApoB in LDL is taken up at receptor sites on extrahepatic cells. ApoK may act as a marker for the uptake of ‘remnant particles’ in certain conditions. For the complete definition of a lipoprotein particle it is necessary to define not only the density and lipid composition but also the apoprotein composition. Immunoassays for most of the 14 or so apoproteins have been developed. These pose technical problems peculiar to lipoproteins. a. Antigen exposure. An antibody raised against a delipidated apoprotein may not fully recognise the apoprotein when it forms part of a lipoprotein. Portions of the apoprotein may be masked by lipid. It may be necessary to delipidate or in some other way break up the lipoprotein before assay. b. The mobility of a complex lipoprotein in an electroimmunoassay may be affected by the size of the particle and by the other protein components of the lipoprotein. In an electroimmunoassay standards should be similar and in a similar matrix to the test solution. It may be shown in the future that assays for (say) plasma apoB. apoAl and apoE will allow more accurate prediction of the risk of developing ischaemic heart disease in the individual than the assays now available for cholesterol, triglyceride and HDL-cholcsterol. but this has not yet been demonstrated.