Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
BBA ReportOn the apoprotein composition of human plasma very low density lipoprotein subfractions
Abstract
Very low density lipoprotein subtractions are heterogeneous in protein content. Different subfractions of very low density lipoproteins contain different proportions of the different very low density lipoprotein apoproteins. These considerations must be taken into account when studying very low density lipoprotein metabolism.
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Cited by (28)
Composition and properties of very low density lipoproteins secreted by the perfused rat liver and subfractionated by affinity chromatography
1987, Biochimica et Biophysica Acta (BBA)/Lipids and Lipid MetabolismVery low density lipoproteins (VLDL) were isolated from the perfusate of rat livers infused with a complex of oleic acid bound to bovine serum albumin. Very low density lipoprotein (VLDL) secretion, bile flow, histopathology, and transmission electron microscopy indicated that secretory functions but not morphologic integrity of the livers were maintained during the procedure. Plasma VLDL and liver perfusate VLDL did not have similar size distribution. VLDL isolated from recycling perfusate and single pass perfusate were also subfractionated with concanavalin A-Sepharose 4B affinity chromatography. Three subfractions were eluted sequentially from the perfusate VLDL: a non-adherent fraction A and two adherent fractions B and C. The size of these VLDL, determined after negative staining and examination by transmission electron microscopy, was significantly decreased by affinity chromatography. VLDL in fractions A, B and C were spherical and had diameters of 935 ± 17, 881 ± 34 and respectively. Fraction A, which did not adhere to the column, contained 65% of the lipid applied to the column. The carbohydrate composition of fraction A VLDL was 11.2 ± 0.6% fucose, 14.7 ± 1.2% galactose, 43.7 ± 2.3% N-acetylglucosamine, and 30.5 ± 1.9% sialic acid. Sugars such as glucose and mannose, which bind to concanavalin A, were not detected. In contrast, VLDL fractions B and C, which adhered to the column, contained both glucose (17.7 and 2.5%) and mannose (5.8 and 8.3%) as well as the other sugars present in VLDL fraction A. Sodium dodecyl sulfate gradient gel electrophoresis revealed that the affinity column procedure clearly altered the apolipoprotein patterns of the applied VLDL, thereby producing abnormal fractions B and C. Fractions B and C also differed from unfractionated VLDL and fraction A VLDL in lipid composition, in surface/interior core lipid ratio, and in fatty acid composition of the interior core lipids, primarily triacylglycerols. The steady-state anisotropy, the limiting anisotropy and the lipid order parameter of fluorescence probe molecules 1,6-diphenyl-1,3,5-hexatriene and trans-parinaric acid incorporated into the VLDL were of the following order: fraction B > fraction A > fraction C. These results are consistent with the interpretation that concanavalin A-Sepharose 4B affinity chromatography may artificially produce a series of VLDL subfractions whose composition and structural properties do not resemble those of native VLDL.
The complete structures of human apolipoprotein B-100 and its messenger RNA
1987, New Comprehensive BiochemistryThis chapter highlights the complete structure of human apolipoprotein B (ApoB)-100 and its messenger RNA. ApoB is an important component in the system of plasma lipoproteins. It functions as the ligand for the low-density lipoprotein (LDL) receptor in peripheral cells, and is a component of plasma chylomicrons (CM), very low-density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low-density lipoproteins (LDL). ApoB-100 is synthesized by the liver and is an obligatory constituent of VLDL, IDL, and LDL. Apo-B is insoluble in both 4.2 M tetramethyl urea and aqueous buffers after extraction with organic solvents. The composition of ApoB following partial tryptic digestion and cyanogen bromide cleavage are all similar to one another. Human plasma LDL contains approximately 80% lipid and 20% protein by weight. About 4–10% of the mass of apoB consists of carbohydrate chains containing galactose, mannose, N-acetylglucosamine, and sialic acid residues. ApoB-100 in LDL is highly immunogenic, and high-titer antibodies against human LDL can be consistently produced by injection of LDL into rabbits.
Structure of triglyceride-rich lipoproteins: An analysis of core and surface phases
1987, New Comprehensive BiochemistryThis chapter describes the structure of triglyceride-rich lipoproteins. Intestinal chylomicrons and hepatic very low-density lipoproteins (VLDL) serve as the major transport vehicles of triglyceride within the circulation. These lipoproteins are collectively designated the “triglyceride-rich “lipoproteins because under normal conditions of diet and time of residence in the plasma triglyceride is their major component. As the content of triglyceride-rich lipoprotein lipids greatly exceeds that of the apoproteins, a reasonable working hypothesis is that the arrangement of the lipids is the key to governing the overall structure of the lipoproteins. The lipids are held together solely by noncovalent forces, and are organized to lessen the unfavorable free energy of contact between hydrophobic lipid moieties and the surrounding water in which they are suspended. Apoproteins are bound to the surface of the lipoproteins, and participate in stabilizing the lipid–water interface. The synthesis of triglyceride-rich lipoproteins occurs within the intracellular membrane compartments of intestinal enterocytes and liver hepatocytes. Nascent chylomicrons and VLDL undergo several major compositional changes after entering the plasma. Both apoproteins and lipids are exchanged between triglyceride-rich lipoproteins and plasma elements such as erythrocytes and other classes of lipoproteins.
Hypertriglyceridemia and carbohydrate intolerance: Interrelations and therapeutic implications
1986, The American Journal of CardiologyAtherosclerosis, the most frequent complication of diabetes, could be the result of hyperlipidemia, among other factors. Mounting evidence suggests that reducing the concentration of triglyceride-rich lipoprotein, which influences the production of the possibly atherogenic intermediate density lipoprotein (IDL), might diminish the circulating level of potentially atherogenic lipoproteins.
Hypertriglyceridemia, even in the absence of obesity, is associated with insulin resistance. To compensate, pancreatic B cells respond to glucose challenge by producing hyperinsulinemia. If the B cells cannot respond adequately, carbohydrate intolerance ensues. Insulin-treated diabetics may also become hyperinsulinemic because routine insulin injection may not reflect physiologic need and because the insulin is administered peripherally rather than portally. Hyperinsulinemia increases the production of circulating triglyceride. It appears to do this in rats by causing the production of more triglyceride-rich lipoprotein particles rather than by increasing the triglyceride content of each particle. Further, at least in rats, the insulin-induced increase in triglyceride production requires the presence of supplementary dietary fructose. Hyperinsulinemia also increases the activity of adipose tissue lipoprotein lipase and the degradation of very low density lipoprotein (VLDL). The concentration of VLDL depends on balance of production and degradation. Accelerated VLDL degradation leads to an increase in IDL production. Because there is mounting evidence that IDL may be atherogenic, this cycle could accelerate atherogenesis. As such, it is reasonable to postulate that reducing the concentration of triglyceride-rich lipoproteins would break this cycle and would diminish the circulating level of potentially atherogenic lipoproteins.
Core modification of human low-density lipoprotein by artificial triacylglycerol emulsion
1985, Biochimica et Biophysica Acta (BBA)/Lipids and Lipid MetabolismTo determine whether an apolipoprotein-free artificial triacylglycerol emulsion can substitute for VLDL in studying cholesterol ester-triacylglycerol exchange processes between triacylglycerol-rich lipoproteins and cholesterol ester-rich lipoproteins, we used Intralipid to modify human plasma LDL. Intralipid was with LDL in the presence of lipoprotein-poor plasma (d > 1.21 g/ml) at 37°C. Intralipid served as an acceptor for cholesterol ester and as a donor of triacylglycerol, modifying the low-density lipoproteins so that triacylglycerol became the major core lipid in the particle — the contribution of cholesterol ester to LDL mass decreased from 38% to 18%, while that of triacylglyeero! increased from 4.9% to 26%, On lipolysis most added LDL triacylglycerol (59–72%) was hydrolyzed, resulting in a smaller particle the ‘native’ LDL particle with net loss of cholesterol ester. Incubation of LDL with the original Intralipid emulsion resulted in modified LDL with a high relative weight of phospholipid (27.7%). oh removal of excess phospholipid from Intralipid and incubation of the resultant ‘washed’ Intralipid with LDL, the relative weight of phospholipid in modified LDL decreased to 20%, which was similar to that observed after incubation of LDL with VLDL. We demonstrate that artificial triacylglycerol emulsion can indeed substitute for VLDL in neutral lipid exchange processes, and further confirm that transfer of core cholesterol ester and triacylglycerol occurs independently of the apolipoproteins present in triacylglycerol-rich lipoproteins and LDL.
Interrelationships among subgroups of serum lipoproteins in normal human subjects
1980, Clinica Chimica ActaAnalytic ultracentrifugation of serum lipoproteins from 80 men and 54 women aged 27–66 was used to determine if specific segments of the high density (HDL), low density (LDL) and very low density (VLDL) lipoprotein schlieren curves could be defined so as to reveal significant correlations among them. Differences in correlations resulted in division of LDL into three subgroups based on flotation rate (S0f 0–7, 7–12, and 12–20) and division of HDL into two subgroups (F01.20 0–1.5 and 2–9).
HDL of F01.20 2–9 (designated HDL2–9) correlated negatively with LDL of S0f 0–7 (LDL0–7) for all groups, positively with LDL of S0f 7–12 except in women aged 27–46, and negatively with VLDL except in men aged 47–66, HDL of F0f 0–1.5 (HDL0–1.5) correlated positively with LDL0–7 except in men aged 27–46 and with VLDL in all but older men. Some correlations were reduced to non-significant levels by controlling for LDL0–7 or VLDL.
Correlations of HDL and LDL flotation subgroups yielded no significant net correlation between total HDL and LDL. Total HDL was directly correlated with HDL1–9 (r > 0.97) but not with HDL0–1.5. The foregoing suggests that decreased HDL represents reduced HDL2–9 and may be accompanied by increased LDL0–7 and VLDL. LDL0–7 may represent an “atherogenic” LDL subclass in part responsible for increased coronary risk associated with low HDL.