Isolation and characterization of two threonine-poor apolipoproteins of human plasma high density lipoproteins

Two apolipoproteins that are minor components normally of human plasma lipoproteins were discovered. They comprise up to 25% or more of the apolipoproteins in high density lipoproteins of some individuals with lipoprotein abnormalities associated with certain metabolic diseases and in individuals treated with amphotericin B for coccidiomycosis infection. The new apolipoproteins are distinctly different in amino acid composition, isoelectric point, and electrophoretic mobility from other known apolipoproteins. The new apolipoproteins are similar in amino acid composition. Both are unusually low in threonine, poor in valine and leucine, and rich in aspartic acid, glycine, alanine, and phenylalanine. They are relatively rich in arginine, although not as rich as the arginine-rich apolipoprotein, and have higher isoelectric points than other apolipoproteins except apoC-I. The more abundant of the two new apolipoproteins, of pI approximately 6.5, exists mainly as a dimeric protein of about 40 000 daltons and is dissociated by mercaptoethanol in the presence of sodium dodecyl sulfate. The less abundant one, of pI approximately 6.0, appears to be about 10 000 daltons. The threonine-poor apolipoproteins are associated mainly with plasma high density lipoproteins, particularly the denser HDL/sub 3/ subfraction, but small amounts were found in the very low and intermediate density lipoproteins. The HDL/sub 3/ with high content of threonine-poor apolipoproteins were indistinguishable from the normal HDL/sub 3/ by agarose or large pore polyacrylamide gel electrophoresis or by analytical ultracentrifugation. The lipid moiety of the abnormal HDL was richer in triglycerides and similar in phospholipid content to that of normal HDL.