The independent synthesis of intermediate density lipoproteins in type III hyperlipoproteinemia.

The kinetics of VLDL (Sf 60-400) and IDL (Sf 12-60) B apoprotein were examined in five type III hyperlipoproteinemic subjects. The production rates for B apoprotein were significantly greater in the IDL fraction than in VLDL. Precursor-product relationships between VLDL and IDL B apoprotein illustrated that a significant proportion of IDL B apoprotein was derived from some source other than VLDL catabolism. These observations indicated that, in the five individuals studied, an 'unusual' B apoprotein synthetic pathway operated whereby B apoprotein was directly entering the IDL fraction. Furthermore, this second pathway resulted in an overproduction of IDL B apoprotein and possibly was the major defect leading to the development of the type III hyperlipoproteinemia lipid profile. In two subjects who were restudied following hormonal treatment (estrogen or thyroxine replacement) and in whom the type III hyperlipoproteinemia lipid profile no longer existed, it was found that the pathway for direct synthesis of IDL B apoprotein had been abolished. From these studies we have concluded that a pathway for the direct synthesis of IDL B apoprotein operates in type III hyperlipoproteinemics and it is a major causative factor in the development of the IDL accumulation characteristic of this metabolic disorder.