Shlomo Eisenberg

Abstract 1. 1. Apolipoprotein-glutamic acid (apoLP-Glu) and apolipoprotein-alanine (apoLP-Ala), small molecular weight apolipoproteins, readily transfer in vitro from very low density lipoprotein to other lipoproteins. Their transfer to high density lipoprotein always exceeds that to low density lipoproteins, and is proportional to the concentration of lipoproteins present in the incubation mixture. A similar transfer of radioactivity occurs in vivo , and is proportional to both plasma triglyceride and high density lipoprotein cholesterol levels. The transfer of apoLP-Glu and apoLP-Ala between very low density and high density lipoproteins is bidirectional, and thus represents, at least in part, an exchange phenomenon. In contrast, the apoprotein moiety of low density lipoprotein does not participate in this type of transfer. 2. 2. Apolipoproteins can be separated into groups following their reassociation properties with lipids and lipoproteins. ApoLP-Glu and apoLP-Ala reassociate with all plasma lipoproteins, predominantly very low density and high density lipoprotein. Apolipoprotein-glutamine 1 (apoLP-Gln 1 ) and apolipoprotein-glutamine 2 (apoLP-Gln 2 ) reassociate primarily with their parent lipoprotein, high density lipoprotein. Representative proteins of both groups however, reassociate with lipid (lecithin or triglyceride). The recombination of apoproteins with lipoproteins thus may be specific and involve a process of “recognition” of the lipoprotein by the apoprotein. This specificity may not be involved in the simple recombination of apolipoproteins and lipids. These observations may explain the distribution of apoproteins among plasma lipoproteins and provide insight into their metabolic fate.

The turnover of (125)I-high density lipoprotein (HDL) was examined in a total of 14 studies in eight normal volunteers in an attempt to determine the metabolic relationship between apolipoproteins A-I (apoA-I) and A-II (apoA-II) of HDL and to define further some of the determinants of HDL metabolism. All subjects were first studied under conditions of an isocaloric balanced diet (40% fat, 40% carbohydrate). Four were then studied with an 80% carbohydrate diet, and two were studied while receiving nicotinic acid (1 g three times daily) and ingesting the same isocaloric balanced diet. The decay of autologous (125)I-HDL and the appearance of urinary radioactivity were followed for at least 2 wk in each study. ApoA-I and apoA-II were isolated by Sephadex G-200 chromatography from serial plasma samples in each study. The specific activities of these peptides were then measured directly. It was found that the decay of specific activity of apoA-I and apoA-II were parallel to one another in all studies. The mean half-life of the terminal portion of decay was 5.8 days during the studies with a balanced diet.Mathematical modeling of the decay of plasma radioactivity and appearance of urinary radioactivity was most consistent with a two-compartment model. One compartment is within the plasma and exchanges with a nonplasma component. Catabolism occurs from both of these compartments. With a balanced isocaloric diet, the mean synthetic rate for HDL protein was 8.51 mg/kg per day. HDL synthesis was not altered by the high carbohydrate diet and was only slightly decreased by nicotinic acid treatment. These perturbations had effects on HDL catabolic pathways that were reciprocal in many respects. With an 80% carbohydrate diet, the rate of catabolism from the plasma compartment rose by a mean of 39.1%; with nicotinic acid treatment, it fell by 42.2%. Changes in the rate of catabolism from the second compartment were generally opposite those in the rate of catabolism from the plasma compartment, suggesting that these two catabolic pathways may be reciprocally regulated.