Low Density Lipoprotein in Man QUANTITATION USING GLUCOSYLATED LOW DENSITY LIPOPROTEIN

A B S T R A C T Low density lipoprotein (LDL) catabolism occurs by LDL receptor-dependent and LDL receptor-independent pathways. We have shown previously that nonenzymatic glucosylation of LDL in the presence of cyanoborohydride irreversibly blocks the lysine residues of LDL. Glucosylated LDL (GLCLDL) was not degraded by the LDL receptor of fibroblasts, and its degradation by macrophages was similar to that of native LDL. This suggested that GLC-LDL should be a good tracer of LDL receptorindependent catabolism, and if combined with a tracer of total LDL catabolism, should enable one to calculate the extent of LDL receptor-dependent catabolism. To determine the contribution of each pathway in man, we prepared '25I-GLC-LDL and ''I-control LDL and simultaneously determined the fractional catabolic rate (FCR) of each tracer in four subjects. In preliminary experiments, we showed that the conditions for glucosylation did not affect LDL turnover. In the four subjects, the FCR for total LDL catabolism ranged from 0.345 to 0.724 d-' with a mean of 0.57±0.16 d-'. The FCR of GLC-LDL varied from 0.071 to 0.141 d-' with a mean of 0.11±0.03 d-'. The latter is similar to the FCR reported for native LDL in subjects with homozygous familial hypercholesterolemia, supporting the interpretation that GLC-LDL traces only the receptor-independent pathway. Despite the wide range of total LDL catabolism in these subjects, LDL receptor-independent catabolism accounted for only 19.5-20.6% of total catabolism. In