IDENTIFICATION OF DISULFIDE-LINKED APOLIPOPROTEIN SPECIES IN HUMAN LIPOPROTEINS

We wished to determine whether apolipoprotein C-II(Toronto), a mutant form of apolipoprotein C-II that contains a C-terminal cysteine residu e, exists as a monomeric species or as multiple disulfide-linked speci es in plasma lipoproteins. The plasma lipoproteins from a heterozygous carrier and two homozygous carriers of apoC-II(Toronto) were investig ated. The mutant apolipoprotein was found in homodimeric form and as h eterodimers with apolipoprotein A-II, apolipoprotein B-100, and apolip oprotein E. Of particular interest was the demonstration of the existe nce of the disulfide-linked species apolipoprotein B-100:A-II and B-10 0:C-II(Toronto) in the very low density and low density lipoproteins i n subjects who were carriers of apoC-II(Toronto). We also observed tha t apoE3:C-II(Toronto) and apoE3:A-II dimers were present in the chylom icrons and very low density lipoproteins of these subjects. The observ ation of the existence of apolipoprotein B-100:A-II was extended to ot her hypercholesterolemic and hypertriglyceridemic subjects. The highes t proportion of apolipoprotein B-100:A-II was observed in the very low density lipoproteins of hypertriglyceridemic subjects. The concentrat ion of this species was significantly higher in hyperlipidemic subject s than in normolipidemic controls. These results demonstrate that the molecular species of cysteine-containing apolipoproteins are complex a nd should be considered in studies of human lipoprotein composition an d function.