Catabolism of Very Low Density Lipoprotein B Apoprotein in Man (original) (raw)
Abstract
The turnover and the catabolic fate of the B apoprotein of very low density lipoprotein (VLDL-B) was studied in 15 normal and hyperlipidemic subjects using reinjected autologous VLDL labeled with radioiodine. The specific radioactivity-time curve of the B apoprotein in total VLDL (Sf20-400) was multiexponential but conformed to a two-pool model during the first 48 h of catabolism. The flux was highest in several hypertriglyceridemic subjects. The mass of pool A exceeded the intravascular content of VLDL-B by 30% on average, indicating extravascular metabolism of VLDL. The two-pool model might reflect the input of several populations of particles or heterogeneity of catabolic processes or pools. The flux of B apoprotein was also measured in several subclasses of VLDL, in smaller intermediate density lipoproteins, and in low density lipoproteins (LDL). In three subjects the flux was similar in Sf 60-400 and in Sf 12-60 lipoproteins, suggesting that VLDL was catabolized at least to a particle in the density range Sf 12-60. Subsequent catabolism appeared to proceed by two pathways: in normotriglyceridemic subjects, B apoprotein flux in the Sf 20-400 and in Sf 12-20 lipoproteins was similar, whereas in hypertriglyceridemic subjects flux through Sf 12-20 accounted for only part of the VLDL-B flux.
The flux of low density lipoprotein B apoprotein (LDL-B), which is believed to be derived from VLDL catabolism, was calculated from the area between the specific activity time curves of VLDL-B and LDL-B. In subjects with normal plasma triglyceride concentration, LDL-B flux was from 91% to 113% of that of VLDL-B; but in three hypertriglyceridemic subjects showing high rates of VLDL-B transport, LDL-B flux was only one-third that of VLDL-B. This suggests that when VLDL-B flux is high, VLDL is substantially catabolized by a route other than through LDL and possibly leaves the circulation as a particle in the Sf 20-60 density range.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barter P. J., Nestel P. J. Precursor-product relationship between pools of very low density lipoprotein triglyceride. J Clin Invest. 1972 Jan;51(1):174–180. doi: 10.1172/JCI106789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beaumont J. L., Carlson L. A., Cooper G. R., Fejfar Z., Fredrickson D. S., Strasser T. Classification of hyperlipidaemias and hyperlipoproteinaemias. Bull World Health Organ. 1970;43(6):891–915. [PMC free article] [PubMed] [Google Scholar]
- Bierman E. L., Albers J. J. Lipoprotein uptake by cultured human arterial smooth muscle cells. Biochim Biophys Acta. 1975 May 22;388(2):198–202. doi: 10.1016/0005-2760(75)90124-1. [DOI] [PubMed] [Google Scholar]
- Bierman E. L., Eisenberg S., Stein O., Stein Y. Very low density lipoprotein "remnant" particles: uptake by aortic smooth muscle cells in culture. Biochim Biophys Acta. 1973 Nov 2;329(1):163–169. doi: 10.1016/0304-4165(73)90021-4. [DOI] [PubMed] [Google Scholar]
- Clifton-Bligh P., Miller N. E., Nestel P. J. Changes in plasma lipoprotein lipids in hypercholesterolaemic patients treated with the bile acid-sequestering resin, colestipol. Clin Sci Mol Med. 1974 Dec;47(6):547–557. doi: 10.1042/cs0470547. [DOI] [PubMed] [Google Scholar]
- Eisenberg S., Bilheimer D. W., Levy R. I., Lindgren F. T. On the metabolic conversion of human plasma very low density lipoprotein to low density lipoprotein. Biochim Biophys Acta. 1973 Dec 20;326(3):361–377. doi: 10.1016/0005-2760(73)90138-0. [DOI] [PubMed] [Google Scholar]
- Eisenberg S., Rachmilewitz D. Interaction of rat plasma very low density lipoprotein with lipoprotein lipase-rich (postheparin) plasma. J Lipid Res. 1975 Sep;16(5):341–351. [PubMed] [Google Scholar]
- Faergeman O., Havel R. J. Metabolism of cholesteryl esters of rat very low density lipoproteins. J Clin Invest. 1975 Jun;55(6):1210–1218. doi: 10.1172/JCI108039. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Faergeman O., Sata T., Kane J. P., Havel R. J. Metabolism of apoprotein B of plasma very low density lipoproteins in the rat. J Clin Invest. 1975 Dec;56(6):1396–1403. doi: 10.1172/JCI108220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fidge N. H., Poulis P. Studies on the radioiodination of very low density lipoprotein obtained from different mammalian species. Clin Chim Acta. 1974 Mar;52(1):15–26. doi: 10.1016/0009-8981(74)90383-0. [DOI] [PubMed] [Google Scholar]
- Fidge N., Poulis P. Studies on the metabolism of rat serum very low density apolipoprotein. J Lipid Res. 1975 Sep;16(5):367–378. [PubMed] [Google Scholar]
- Fredrickson D. S., Levy R. I., Lees R. S. Fat transport in lipoproteins--an integrated approach to mechanisms and disorders. N Engl J Med. 1967 Feb 2;276(5):273–concl. doi: 10.1056/NEJM196702022760507. [DOI] [PubMed] [Google Scholar]
- GURPIDE E., MANN J., SANDBERG E. DETERMINATION OF KINETIC PARAMETERS INA TWO-POOL SYSTEM BY ADMINISTRATION OF ONE OR MORE TRACERS. Biochemistry. 1964 Sep;3:1250–1255. doi: 10.1021/bi00897a012. [DOI] [PubMed] [Google Scholar]
- GUSTAFSON A., ALAUPOVIC P., FURMAN R. H. STUDIES OF THE COMPOSITION AND STRUCTURE OF SERUM LIPOPROTEINS: ISOLATION, PURIFICATION, AND CHARACTERIZATION OF VERY LOW DENSITY LIPOPROTEINS OF HUMAN SERUM. Biochemistry. 1965 Mar;4:596–605. doi: 10.1021/bi00879a033. [DOI] [PubMed] [Google Scholar]
- HAVEL R. J. Conversion of plasma free fatty acids into triglycerides of plasma lipoprotein fractions in man. Metabolism. 1961 Dec;10:1031–1034. [PubMed] [Google Scholar]
- HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamilton R. L. Synthesis and secretion of plasma lipoproteins. Adv Exp Med Biol. 1972;26(0):7–24. doi: 10.1007/978-1-4684-7547-0_2. [DOI] [PubMed] [Google Scholar]
- Havel R. J., Shore V. G., Shore B., Bier D. M. Role of specific glycopeptides of human serum lipoproteins in the activation of lipoprotein lipase. Circ Res. 1970 Oct;27(4):595–600. doi: 10.1161/01.res.27.4.595. [DOI] [PubMed] [Google Scholar]
- Hazzard E. R., Bierman E. L. The spectrum of electrophoretic mobility of very low density lipoproteins: role of slower migrating species in endogenous hypertriglyceridemia (type IV hyperlipoproteinemia) and broad-beta disease (type III). J Lab Clin Med. 1975 Aug;86(2):239–252. [PubMed] [Google Scholar]
- Homma Y., Nestel P. J. Changes in plasma lipoprotein constituents during constant infusions of heparin. Atherosclerosis. 1975 Nov-Dec;22(3):551–563. doi: 10.1016/0021-9150(75)90033-7. [DOI] [PubMed] [Google Scholar]
- Illingworth D. R. Metabolism of lipoproteins in nonhuman primates. Studies on the origin of low density lipoprotein apoprotein in the plasma of the squirrel monkey. Biochim Biophys Acta. 1975 Apr 18;388(1):38–51. doi: 10.1016/0005-2760(75)90060-0. [DOI] [PubMed] [Google Scholar]
- Kane J. P. A rapid electrophoretic technique for identification of subunit species of apoproteins in serum lipoproteins. Anal Biochem. 1973 Jun;53(2):350–364. doi: 10.1016/0003-2697(73)90081-x. [DOI] [PubMed] [Google Scholar]
- Kane J. P., Sata T., Hamilton R. L., Havel R. J. Apoprotein composition of very low density lipoproteins of human serum. J Clin Invest. 1975 Dec;56(6):1622–1634. doi: 10.1172/JCI108245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Langer T., Strober W., Levy R. I. The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia. J Clin Invest. 1972 Jun;51(6):1528–1536. doi: 10.1172/JCI106949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mjos O. D., Faergeman O., Hamilton R. L., Havel R. J. Characterization of remnants produced during the metabolism of triglyceride-rich lipoproteins of blood plasma and intestinal lymph in the rat. J Clin Invest. 1975 Sep;56(3):603–615. doi: 10.1172/JCI108130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ostlund-Lindqvist A. M., Iverius P. H. Activation of highly purified lipoprotein lipase from bovine milk. Biochem Biophys Res Commun. 1975 Aug 18;65(4):1447–1455. doi: 10.1016/s0006-291x(75)80391-3. [DOI] [PubMed] [Google Scholar]
- Reichl D., Simons L. A., Myant N. B., Pflug J. J., Mills G. L. The lipids and lipoproteins of human peripheral lymph, with observations on the transport of cholesterol from plasma and tissues into lymph. Clin Sci Mol Med. 1973 Sep;45(3):313–329. doi: 10.1042/cs0450313. [DOI] [PubMed] [Google Scholar]
- Ruderman N. B., Jones A. L., Krauss R. M., Shafrir E. A biochemical and morphologic study of very low density lipoproteins in carbohydrate-induced hypertriglyceridemia. J Clin Invest. 1971 Jun;50(6):1355–1368. doi: 10.1172/JCI106615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sigurdsson G., Nicoll A., Lewis B. Conversion of very low density lipoprotein to low density lipoprotein. A metabolic study of apolipoprotein B kinetics in human subjects. J Clin Invest. 1975 Dec;56(6):1481–1490. doi: 10.1172/JCI108229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sigurdsson G., Nicoll A., Lewis B. Metabolism of very low density lipoproteins in hyperlipidaemia: studies of apolipoprotein B kinetics in man. Eur J Clin Invest. 1976 Mar 31;6(2):167–177. doi: 10.1111/j.1365-2362.1976.tb00508.x. [DOI] [PubMed] [Google Scholar]
- Sigurdsson G., Nicoll A., Lewis B. The metabolism of low density lipoprotein in endogenous hypertriglyceridaemia. Eur J Clin Invest. 1976 Mar 31;6(2):151–158. doi: 10.1111/j.1365-2362.1976.tb00506.x. [DOI] [PubMed] [Google Scholar]
- Stein O., Rachmilewitz D., Sanger L., Eisenberg S., Stein Y. Metabolism of iodinated very low density lipoprotein in the rat. Autoradiographic localization in the liver. Biochim Biophys Acta. 1974 Aug 22;360(2):205–216. doi: 10.1016/0005-2760(74)90170-2. [DOI] [PubMed] [Google Scholar]
- Tytgat G. N., Rubin C. E., Saunders D. R. Synthesis and transport of lipoprotein particles by intestinal absorptive cells in man. J Clin Invest. 1971 Oct;50(10):2065–2078. doi: 10.1172/JCI106700. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Windmueller H. G., Herbert P. N., Levy R. I. Biosynthesis of lymph and plasma lipoprotein apoproteins by isolated perfused rat liver and intestine. J Lipid Res. 1973 Mar;14(2):215–223. [PubMed] [Google Scholar]
- ZILVERSMIT D. B. The design and analysis of isotope experiments. Am J Med. 1960 Nov;29:832–848. doi: 10.1016/0002-9343(60)90117-0. [DOI] [PubMed] [Google Scholar]