Skip to main content

Summary

Lipids are transported in the blood in four major classes of lipoproteins. The triacylglycerol-rich lipoproteins are chylomicrons and very-low-density lipoproteins (VLDL) which are produced by the small intestine and liver, respectively. These lipoproteins mainly carry fatty acids to adipose tissue and muscle where the triacylglycerol is hydrolysed by lipoprotein lipase. The resulting particles that remain in the blood are chylomicron remnants and low-density lipoprotein (LDL), respectively. The remnant is taken up by the liver via endocytosis which is mediated by a specific receptor for apolipoprotein E (apoE). LDL, which are rich in cholesterol, can also be taken up by the liver or extrahepatic tissues by a receptor-mediated endocytosis that specifically recognises apoB or apoE. ‘Nascent’ high-density lipoprotein (HDL) particles are secreted by the liver and intestine and then undergo modification to become HDL3 and then HDL2 as they acquire cholesterol ester. They facilitate the reverse transport of cholesterol back to the liver.

Little is known of the hormonal regulation of lipoprotein uptake by the liver. Recently, we have shown that insulin and tri-iodothyronine (T3) increase the specific binding of LDL to cultured hepatocytes whereas dexamethasone (a synthetic glucocorticoid) has the opposite effect. The changes in binding produced by insulin and dexamethasone are paralleled by alterations in the rate of degradation of apoB. These findings may in part explain the hypercholesterolaemia and increased risk of premature atherosclerosis that can be associated with poorly controlled diabetes or hypothyroidism.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anderson, D. W., Nichols, A. V., Pan, S. S. and Lindgren, F. T. High-density lipoprotein distribution-resolution and determination of three major components in a normal population sample. Atherosclerosis 29 (1978) 161–179

    Article  PubMed  CAS  Google Scholar 

  • Bachorik, P. S., Franklin, F. A., Virgil, D. G. and Kwiterovich, P. O. High affinity uptake and degradation of apolipoprotein E free high-density lipoprotein and low-density lipoprotein in cultured porcine hepatocytes. Biochemistry 21 (1982) 5675–5684

    Article  PubMed  CAS  Google Scholar 

  • Bengtsson, G. and Olivecrona, T. Lipoprotein lipase: Some effects of activator proteins. Eur. J. Biochem. 106 (1980) 549–555

    Article  PubMed  CAS  Google Scholar 

  • Brown, M. S., and Goldstein, J. L. Lipoprotein receptors in the liver. Control signals for cholesterol traffic. J. Clin. Invest. 72 (1983) 743–747

    Article  PubMed  CAS  Google Scholar 

  • Carew, T. E., Pittman, R. C. and Steinberg, D. Tissue sites of degradation of native and reductively methylated [14C]sucrose-labelled low-density lipoprotein in rats. Contribution of receptor-dependent and receptor-independent pathways. J. Biol. Chem. 257 (1982) 8001–8008

    PubMed  CAS  Google Scholar 

  • Chapman, J. M. Comparative analysis of mammalian plasma lipoproteins. In Segrest, J. P. and Albers, J. J. (eds.). Methods in Enzymology 128. Plasma Lipoproteins. Part A. Preparation, Structure and Molecular Biology, Academic Press, New York, (1986) 70–147

    Google Scholar 

  • Cryer, A. Tissue lipoprotein lipase activity and its action in lipoprotein metabolism. Int. J. Biochem. 13 (1981) 525–541

    Article  PubMed  CAS  Google Scholar 

  • Durrington, P. N., Newton, R. S., Weinstein, A. B. and Steinberg, D. Effects of insulin and glucose on very low density lipoprotein secretion by cultured rat hepatocytes. J. Clin. Invest. 70 (1982) 63–73

    Article  PubMed  CAS  Google Scholar 

  • Edge, S. B., Hoeg, J. M., Triche, T., Schneider, P. D. and Brewer, H. B. Cultured human hepatocytes. Evidence for metabolism of low-density lipoproteins by a pathway independent of the classical low-density lipoprotein receptor. J. Biol. Chem. 261 (1986) 3800–3806

    PubMed  CAS  Google Scholar 

  • Eisenberg, S. High-density lipoprotein metabolism. J. Lipid Res. 25 (1984) 1017–1058

    PubMed  CAS  Google Scholar 

  • Fielding, C. J. and Fielding, P. E. Cholesterol transport between cells and body fluids. Role of plasma lipoproteins and the plasma cholesterol esterification system. Med. Clin. North. Am. 66 (1982) 363–373

    PubMed  CAS  Google Scholar 

  • Fong, B. S., Rodrigues, P. O., Salter, A. M., Yip, B. P., Despres, J. P., Gregg, R. E. and Angel, A. Characterization of high-density lipoprotein binding to human adipocyte plasma membranes. J. Clin. Invest. 75 (1985) 1804–1812

    Article  PubMed  CAS  Google Scholar 

  • Fong, B. S., Salter, A. M., Jimenez, J. and Angel, A. The role of apolipoprotein AI and apolipoprotein AII in high-density lipoprotein binding to human adipocyte plasma membranes. Biochim. Biophys. Acta 920 (1987) 105–113

    Article  PubMed  CAS  Google Scholar 

  • Glass, C., Pittman, R. C., Weinstein, D. B. and Steinberg, D. Dissociation of tissue uptake of cholesterol ester from that of apoprotein AI of rat plasma high-density lipoprotein: Selective delivery of cholesterol ester to liver, adrenal, and gonad. Proc. Natl. Acad. Sci. USA 80 (1983) 5435–5439

    Article  PubMed  CAS  Google Scholar 

  • Goldstein, J. L. and Brown, M. S. The low-density lipoprotein pathway and its relation to atherosclerosis. Annu. Rev. Biochem. 46 (1977) 897–930

    Article  PubMed  CAS  Google Scholar 

  • Goldstein, J. L., Kita, T. and Brown, M. S. Defective lipoprotein receptors and atherosclerosis. Lessons from an animal counterpart of familial hypercholesterolemia. N. Engl. J. Med. 309 (1983) 288–296

    Article  PubMed  CAS  Google Scholar 

  • Green, P. H. R., Tall, A. R. and Glickman, R. M. Rat intestine secretes discoidal high-density lipoprotein. J. Clin. Invest. 61 (1978) 528–534

    Article  PubMed  CAS  Google Scholar 

  • Graham, D. L. and Oram, J. F. Identification and characterization of a high-density lipoprotein binding protein in cell membranes by ligand blotting. J. Biol. Chem. 262 (1987) 7439–7442

    PubMed  CAS  Google Scholar 

  • Gwynne, J. T. and Strauss, J. F. The role of lipoproteins in steroidogenesis and cholesterol metabolism in steroidogenic glands. Endocrinol. Rev. (1982) 299–329

    Google Scholar 

  • Hamilton, R. L., Williams, M. C., Fielding, C. J. and Havel, R. J. Discoidal bilayer structure of nascent high-density lipoproteins from perfused rat liver. J. Clin. Invest. 58 (1976) 667–680

    Article  CAS  Google Scholar 

  • Havekes, L. M., Schouten, D., deWit, E. C. M., Cohen, L. H., Griffioen, M., van Hinsbergh, V. W. M. and Princen, H. M. G. Stimulation of the LDL receptor activity in the human hepatoma cell line HepG2 by high-density serum fractions. Biochim. Biophys. Acta 875 (1986) 236–246

    Article  PubMed  CAS  Google Scholar 

  • Havel, R. J., Kane, J. P. and Kashyap, M. L. Interchange of apolipoproteins between chylomicrons and high-density lipoproteins during alimentary lipemia in man. J. Clin. Invest. 52 (1973) 32–38

    Article  PubMed  CAS  Google Scholar 

  • Havel, R. J. Role of the liver in atherosclerosis. Arteriosclerosis 5 (1985) 569–580

    Article  PubMed  CAS  Google Scholar 

  • Heimberg, M., Olubadewo, J. O. and Wilcox, H. G. Plasma lipoproteins and regulation of hepatic metabolism of fatty acids in altered thyroid states. Endocrine Rev. (1985) 590–607

    Google Scholar 

  • Hoeg, J. M., Edge, S. B., Demonsky, S. J., Starzl, T. E., Triche, T., Gregg, R. E. and Brewer, H. B. Metabolism of low-density lipoproteins by cultured hepatocytes from normal and homozygous familial hypercholesterolemic subjects. Biochim. Biophys Acta 876 (1986) 646–657

    Article  PubMed  CAS  Google Scholar 

  • Hui, D. Y., Innerarity, T. L. and Mahley, R. W. Lipoprotein binding to canine hepatic membranes. Metabolically distinct apoE and apoB, E receptors. J. Biol. Chem. 256 (1981) 5646–5655

    PubMed  CAS  Google Scholar 

  • Jackson, R. L., Pattus, F. and DeHaas, G. Mechanism of action of milk lipoprotein lipase at substrate interfaces: Effects of apolipoproteins. Biochemistry 19 (1980) 373–378

    Article  PubMed  CAS  Google Scholar 

  • Kita, T., Brown, M. S., Bilheimer, D. W. and Goldstein, J. L. Delayed clearance of very low density and intermediate density lipoproteins with enhanced conversion to low density lipoprotein in WHHL rabbits. Proc. Natl. Acad. Sci. USA 79 (1982) 5693–5697

    Article  PubMed  CAS  Google Scholar 

  • Laker, M. E. and Mayes, P. A. Investigations into the direct effects of insulin on hepatic ketogenesis, lipoprotein secretion and pyruvate dehydrogenase activity. Biochim. Biophys. Acta 795 (1984) 427–430

    Article  PubMed  CAS  Google Scholar 

  • Mahley, R. W. and Innerarity, T. L. Lipoprotein receptors and cholesterol homeostasis. Biochim. Biophys. Acta 737 (1983) 197–222

    Article  PubMed  CAS  Google Scholar 

  • Mangiapane, E. H. and Brindley, D. N. Effects of dexamethasone and insulin on the synthesis of triacylglycerols and phosphatidylcholine by monolayer cultures of rat hepatocytes. Biochem. J. 233 (1986) 151–160

    PubMed  CAS  Google Scholar 

  • Miller, G. J. and Miller, N. E. Plasma high-density lipoprotein concentration and development of ischaemic heart disease. Lancet 1 (1975) 16–19

    Article  PubMed  CAS  Google Scholar 

  • Nestruck, A., Christine, A. N. D. and Rubinstein, D. The synthesis of apoproteins of very low density lipoproteins isolated from the Golgi apparatus of rat liver. Can. J. Biochem. 54 (1976) 617–628

    Article  PubMed  CAS  Google Scholar 

  • Oram, J. F., Albers, J. J., Cheung, M. C. and Bierman, E. L. The effects of subfractions of high-density lipoprotein on cholesterol efflux from cultured fibroblasts. J. Biol. Chem. 256 (1981) 8348–8356

    PubMed  CAS  Google Scholar 

  • Oram, J. F. Effects of high-density lipoprotein subfractions on cholesterol homeostasis in human fibroblasts and arterial smooth muscle cells. Arteriosclerosis 3 (1983) 420–432

    Article  PubMed  CAS  Google Scholar 

  • Ose, L., Ose, T., Norum, K. R. and Berg, T. Uptake and degradation of 125I-labelled high-density lipoproteins in rat liver cells in vivo and in vitro. Biochim. Biophys. Acta 574 (1979) 521–536

    Article  PubMed  CAS  Google Scholar 

  • Patsch, J. R., Gotto, A. M. Jr, Olivecrona, T. and Eisenberg, S. Formation of high-density lipoprotein 2-like particles during lypolysis of very low density lipoproteins in vitro. Proc. Natl. Acad. Sci. USA 75 (1978) 4519–4528

    Article  PubMed  CAS  Google Scholar 

  • Patsch, W., Franz, S. and Schonfeld, G. Role of insulin in lipoprotein secretion by cultured rat hepatocytes. J. Clin. Invest. 71 (1983) 1161–1174

    Article  PubMed  CAS  Google Scholar 

  • Pullinger, C. R. and Gibbons, G. F. Effects of hormones and pyruvate on the rates of secretion of very-low-density lipoprotein triacylglycerol and cholesterol by rat hepatocytes. Biochim. Biophys. Acta 833 (1985) 44–51

    Article  PubMed  CAS  Google Scholar 

  • Redgrave, T. G. and Small, D. M. Quantitation of the transfer of surface phospholipid of chylomicrons to the high-density lipoprotein fraction during the catabolism of chylomicrons in the rat. J. Clin. Invest. 64 (1979) 162–171

    Article  PubMed  CAS  Google Scholar 

  • Rifici, V. A. and Eder, H. A. A hepatocyte receptor for high-density lipoproteins specific for apolipoprotein A-l. J. Biol. Chem. 259 (1984) 13814–13818

    PubMed  CAS  Google Scholar 

  • Salter, A. M., Saxton, J. and Brindley, D. N. Characterization of the binding of human low-density lipoprotein to primary monolayer cultures of rat hepatocytes. Biochem. J. 240 (1986) 549–557

    PubMed  CAS  Google Scholar 

  • Salter, A. M., Bugaut, M., Saxton, J., Fisher, S. C. and Brindley, D. N. Effects of preincubation of primary monolayer cultures of rat hepatocytes with low- and high-density lipoproteins on the subsequent binding and metabolism of human low-density lipoprotein. Biochem. J. 247 (1987a) 79–84

    PubMed  CAS  Google Scholar 

  • Salter, A. M., Fong, B. S., Jimenez, J., Rotstein, L. and Angel, A. Regional variation in high density lipoprotein binding to human adipocyte plasma membranes of massively obese subjects. Eur. J. Clin. Invest. 17 (1987b) 16–22

    Article  PubMed  CAS  Google Scholar 

  • Salter, A. M., Fisher, S. C. and Brindley, D. N. Binding of low-density lipoprotein to monolayer cultures of rat hepatocytes is increased by insulin and decreased by dexamethasone. FEBS Lett. 220 (1987c) 159–162

    Article  PubMed  CAS  Google Scholar 

  • Salter, A. M., Fisher, S. C. and Brindley, D. N. Interactions of triiodothyronine, insulin and dexamethasone on the binding of human LDL to rat hepatocytes in monolayer culture. Atherosclerosis 71 (1988) 77–80

    Article  PubMed  CAS  Google Scholar 

  • Salter, A. M., Saxton, J. and Brindley, D. N. Characterization of the binding of human low-density lipoprotein to cultured rat hepatocytes. Biochem. Soc. Trans. 15 (1987d) 253–254

    CAS  Google Scholar 

  • Schmitz, G., Niemann, R., Brennhausen, B., Krausse, R. and Assman, G. Regulation of high-density lipoprotein receptors in cultured macrophages: role of acyl-CoA: cholesterol acyltransferase. EMBO J. 4 (1985) 2773–2779

    PubMed  CAS  Google Scholar 

  • Schonfeld, G., Bell, E. and Alpers, D. H. Intestinal apoproteins during fat absorption. J. Clin. Invest. 61 (1978) 1539–1550

    Article  PubMed  CAS  Google Scholar 

  • Scott, J., Pease, R. J., Powell, L. M., Wallis, S. C., McCarthy, B. J., Mahley, R. W., Levy-Wilson, B. and Knott, T. J. Human apolipoprotein-B: complete cDNA sequence and identification of structural domains of the protein. Biochem. Soc. Trans. 15 (1987) 195–199

    PubMed  CAS  Google Scholar 

  • Sherrill, B. C., Innerarity, T. L. and Mahley, R. W. Rapid hepatic clearance of the canine lipoproteins containing only the E apoprotein by a high affinity receptor. J. Biol. Chem. 255 (1980) 1804–1807

    PubMed  CAS  Google Scholar 

  • Soltys, P. A., Portman, O. W. and O’Malley, J. L. Binding properties of high-density lipoprotein subfractions and low-density lipoproteins of rabbit hepatocytes. Biochem. Biophys. Acta 713 (1982) 300–314

    Article  PubMed  CAS  Google Scholar 

  • Spady, D. K., Bilheimer, D. W. and Dietschy, J. M. Rates of receptor-dependent and -independent low-density lipoprotein uptake in the hamster. Proc. Natl. Acad. Sci. USA 80 (1983) 3499–3503

    Article  PubMed  CAS  Google Scholar 

  • Spady, D. K., Turley, S. D. and Dietschy, J. M. Receptor-independent low-density lipoprotein transport in rat in vivo. Quantitation, characterization, and metabolic consequences. J. Clin. Invest. 76 (1985) 1113–1122

    Article  PubMed  CAS  Google Scholar 

  • Sparks, C. F., Sparks, J. D., Bolognino, M., Salhanick, A., Strumph, P. S. and Amatruda, J. M. Insulin effects on apolipoprotein synthesis by primary cultures of rat hepatocytes. Metabolism 35 (1986) 1128–1136

    Article  PubMed  CAS  Google Scholar 

  • Stalenhoef, A. F. H., Malloy, M. J., Kane, J. P. and Havel, R. J. Metabolism of apolipoproteins B-48 and B-100 of triglyceride-rich lipoproteins in patients with familial dysbetalipoproteinemia. J. Clin. Invest. 78 (1986) 722–728

    Article  PubMed  CAS  Google Scholar 

  • Swift, L. L., Manowitz, N. R., Dunn, G. D. and LeQuire, V. S. Isolation and characterization of hepatic Golgi lipoproteins from hypercholesterolemic rats. J. Clin. Invest. 66 (1980) 415–425

    Article  PubMed  CAS  Google Scholar 

  • Topping, D. L. and Mayes, P. A. The immediate effects of insulin and fructose on the metabolism of the perfused liver. Changes in lipoprotein secretion, fatty acid oxidation and esterification, lipogenesis and carbohydrate metabolism. Biochem. J. 126 (1972) 295–311

    PubMed  CAS  Google Scholar 

  • Underwood, A. H., Emmett, J. C., Ellis, D., Flynn, S. B., Leeson, P. D., Benson, G. M,, Novelli, R., Pearce, N. J. and Shah, V. P. A thyromimetic that decreases plasma cholesterol levels without increasing cardiac activity. Nature 324 (1986) 425–429

    Article  PubMed  CAS  Google Scholar 

  • Walton, K. W., Scott, P. J., Dykes, P. W. and Davies, J. W. L. The significance of alteration in serum lipids in thyroid dysfunction. Part 2 (Alteration in metabolism and turnover of 131I-low density lipoproteins in hypothyroidism and thyrotoxicosis). Clin. Sci. 29 (1965) 217–238

    PubMed  CAS  Google Scholar 

  • Weisgraber, K. H. and Mahley, R. W. Subfractionation of human high-density lipoproteins by heparin-Sepharose affinity chromatography. J. Lipid Res. 21 (1980) 316–325

    PubMed  CAS  Google Scholar 

  • Whitton, P. D. and Hems, D. A. Glycogen synthesis in perfused liver of adrenalectomized rats. Biochem. J. 156 (1976) 585–592

    PubMed  CAS  Google Scholar 

  • Woodside, W. F. and Heimberg, M. Effects of anti-insulin serum, insulin and glucose on output of triglycerides and on ketogenesis by perfused rat liver. J. Biol. Chem. 251 (1976) 13–23

    PubMed  CAS  Google Scholar 

  • Zilversmit, D. B. Assembly of chylomicrons in the intestine cell. In Dietschy, J. M. Gotto, A. M. and Ontko, J. A. (eds.) Disturbances of Lipid and Lipoprotein Metabolism, American Physiological Society, Bethesda, (1978) 69–81

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

R. J. Pollitt R. A. Harkness G. M. Addison

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Salter, A.M., Brindley, D.N. (1988). The Biochemistry of Lipoproteins. In: Pollitt, R.J., Harkness, R.A., Addison, G.M. (eds) Studies in Inherited Metabolic Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-1259-5_1

Download citation

  • DOI: https://doi.org/10.1007/978-94-009-1259-5_1

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-7059-1

  • Online ISBN: 978-94-009-1259-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics