Structure and Evolution of the Apolipoprotein and Lipase Gene Families

  • L. Chan
  • W. Hide
  • Yau-Wen Yang
  • Wen-Hsiung Li
Part of the Argenteuil Symposia book series (ARGENTEUIL)


The plasma lipoproteins are the transport vehicles that deliver lipids from the liver and intestine to the peripheral tissues for disposal, and in turn, they capture some of the peripherally derived lipids and return them to the liver, where they are metabolized. Lipoprotein lipase (LPL) and hepatic triglyceride Lipase (HL) are enzymes located on the vascular endothelial surface that modify, through lipid hydrolysis, the circulating lipoprotein particles. On the surface of these particles are the apolipoproteins, the protein constitutents which are essential for the structure and stability of the different lipoprotein classes. In addition to their structural role, the apolipoproteins also serve other diverse functions, e.g. as ligands for specific cell surface receptors (apo E and apo B-100) and enzyme activators (apo C-II and apo A-I).


Pancreatic Lipase Human Apolipoprotein Exon Shuffling High Substitution Rate Hepatic Triglyceride Lipase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aggerbeck LP, Wetterau KH, Weisgraber C-S, Wu C, Lindgren FT (1988) Human apolipoprotein E3 in aqueous solution. II. Properties of the amino-and carboxyl-terminal domains. J Biol Chem 263:6249–6258PubMedGoogle Scholar
  2. Ameis D, Stahnke G, Kobayashi J (1990) Isolation and characterization of the human hepatic lipase gene. J Biol Chem 265:6652–6555Google Scholar
  3. Barker WC, Dayhoff MO (1977) Evolution of lipoproteins deduced from protein sequence data. Comp Biochem Physiol 576:309–315Google Scholar
  4. Bengtsson-Olivecrona G, Olivecrona T, Jörnvall H (1986) Lipoprotein lipases from cow, guinea-pig and man: structural characterization and identification of protease-sensitive internal regions. Eur J Biochem 161:281–288PubMedCrossRefGoogle Scholar
  5. Boguski MS, Elshourbagy N, Taylor JM, Gordon JI (1984) Rat apolipoprotein A-IV contains 13 tandem repetitions of a 22 amino acid segment with amphipathic helical potential. Proc Natl Acad Sci USA 81:5021–5025PubMedCrossRefGoogle Scholar
  6. Boguski MS, Elshourbagy N, Taylor JM, Gordon JI (1985) Comparative analysis of repeated sequences in rat apolipoproteins A-I, A-IV and E. Proc Natl Acad Sci USA 82:992–996PubMedCrossRefGoogle Scholar
  7. Boguski MS, Freeman M, Elshourbagy NA, Taylor JM, Gordon JI (1986) On computer-assisted analysis of biological sequences: proline puncutation, consensus sequences, and apolipoprotein repeats. J Lipid Res 27:1011–1034PubMedGoogle Scholar
  8. Brenner S (1988) The molecular evolution of genes and proteins: a tale of two serines. Nature 334:528–530PubMedCrossRefGoogle Scholar
  9. Cai S-J, Wong DM, Chen S-H, Chan L (1989) Structure of the human hepatic triglyceride lipase gene. Biochemistry 28:8966–8971PubMedCrossRefGoogle Scholar
  10. Chaillan C, Abousalam K, Kerfelec B et al. (1990) Horse pancreatic lipase and colipase. CEC-GBF International Workshop, Braunschweig, GermanyGoogle Scholar
  11. Das HK, McPherson J, Bruns GAP, Karathanasis SK, Breslow JL (1985) Isolation, characterization and mapping to chromosome 19 of the human apolipoprotein E gene. J Biol Chem 260:6240–6247PubMedGoogle Scholar
  12. Datta S, Luo C-C, Li W-H et al. (1988) Human hepatic lipase: cloned cDNA sequence, restriction fragment length polymorphisms, chromosomal localization and evolutionary relationships with lipoprotein lipase and pancreatic lipase. J Biol Chem 263:1107–1110PubMedGoogle Scholar
  13. Dayhoff MO (1978) Atlas of protein sequence and structure (vol 5). National Biomedical Research Foundation, Silver Spring, MarylandGoogle Scholar
  14. Elshourbagy NA, Walker DW, Boguski MS, Gordon JI, Taylor JM (1986) The nucleotide and derived amino acid sequence of human apolipoprotein A-IV mRNA and the close linkage of its gene to the genes of apolipoproteins A-I and C-III. J Biol Chem 261:1998–2002PubMedGoogle Scholar
  15. Fitch WM (1977) Phylogenetics constrained by the cross-over process as illustrated by human hemoglobins and a thirteen cycle, eleven amino acid repeat in human apolipoprotein A-I. Genetics 86:623–644PubMedGoogle Scholar
  16. Fukushima D, Kupferberg JP, Yokoyama S, Kroon DJ, Kaiser ET, Kezdy FJ (1979) A synthetic amphipathic helical docasapeptide with the surface properties of plasma apolipoprotein A-I. Am Chem Soc 101:3703–3704CrossRefGoogle Scholar
  17. Havel RJ, Kane JP, Kashyap ML (1973) Interchange of apolipoproteins between chylomicrons and high density lipoproteins during alimentary lipemia in man. J Clin Invest 52:32–38PubMedCrossRefGoogle Scholar
  18. Kaiser ET, Kezdy FJ (1983) Secondary structures of proteins and peptides in amphipathic environments (a review). Proc Natl Acad Sci USA 80:1137–1143PubMedCrossRefGoogle Scholar
  19. Karathanasis SK, Zannis VI, Breslow JL (1983) Isolation and characterization of the human apolipoprotein A-I gene. Proc Natl Acad Sci USA 80:6147–6151PubMedCrossRefGoogle Scholar
  20. Karathanasis SK, Yunis I, Zannis VI (1986) Structure, evolution, and tissue-specific synthesis of human apolipoprotein A-IV. Biochemistry 25:3962–3970PubMedCrossRefGoogle Scholar
  21. Komaromy MC, Schotz ME (1987) Cloning of rat hepatic lipase cDNA: evidence for a lipase gene family. Proc Natl Acad Sci USA 84:1526–1530PubMedCrossRefGoogle Scholar
  22. Lalazar A, Weisgraber KH, Rall SC Jr et al. (1988) Site specific mutagenesis of human apolipoprotein E: receptor binding activity of variants with single amino acid substitutions. J Biol Chem 263:3542–3545PubMedGoogle Scholar
  23. Li W-H, Wu C-I, Luo, C-C (1985) A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Mol Biol Evol 2:150–174PubMedGoogle Scholar
  24. Li W-H, Tanimura M, Sharp PM (1987) An evaluation of the molecular clock hypothesis using mammalian DNA sequnces. J Mol Evol 25:330–342PubMedCrossRefGoogle Scholar
  25. Li W-H, Gouy M, Sharp PM, O’hUigin C, Yang Y-W (1990) Molecular phylogeny of rodentia, lagomorpha, primates, ardiodactyla, and carnivora and molecular clock. Proc Natl Acad Sci USA 87:6703–6707PubMedCrossRefGoogle Scholar
  26. Luo C-C, Li W-H, Moore MN, Chan L (1986) Structure and evolution of the apolipoprotein multigene family. J Mol Biol 187:325–340PubMedCrossRefGoogle Scholar
  27. Luo C-C, Li W-H, Chan L (1989) Structure and expression of dog apolipoprotein A-I, E, and C-I mRNAs: implications for the evolution and functional constraints of apolipoprotein structure. J Lipid Res 30:1735–1746PubMedGoogle Scholar
  28. Mahley RW (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240:522–530CrossRefGoogle Scholar
  29. Mahley RW, Innerarity TL (1983) Lipoprotein receptors and cholesterol homeostasis. Biochim Biophys Acta 737:197–222PubMedGoogle Scholar
  30. McLahlan AD (1977) Repeated helical pattern in apolipoprotein A-I. Nature 267:465–466CrossRefGoogle Scholar
  31. Nakagawa SH, Lau HSH, Kezdy FJ, Kaiser ET (1985) The use of polymer-bound oximes for the synthesis of large peptides usable in segment condensation: synthesis of a 44 amino acid amphipathic peptide model of apolipoprotein A-I. J Am Chem Soc 107:7087–7092CrossRefGoogle Scholar
  32. Novacek MJ (1982) Information for molecular studies from anatomical and fossil evidence on higher eutherian phylogeny. In: Goodman M (ed) Macromolecular sequences in systematic and evolutionary biology. Plenum Press, New York, pp 3–41Google Scholar
  33. O’hUigin CO, Chan L, Li W-H (1990) Cloning and sequencing of bovine apolipoprotein A-I cDNA and molecular evolution of apolipoproteins A-I and B-100. Mol Biol Evol 7:327–339Google Scholar
  34. Persson B, Bengtsson-Olivecrona G, Enerbäck S, Olivecrona T, Jöravall H (1989) Structural features of lipoprotein lipase. Eur J Biochem 179:39–45PubMedCrossRefGoogle Scholar
  35. Rogers J (1985) Exon shuffling and intron insertion in serine protease genes. Nature (Lond) 315:458–459CrossRefGoogle Scholar
  36. Semenkovich CF, Wims M, Noe L, Etienne J, Chan L (1989) Insulin regulation of lipoprotein lipase activity in 3T3-L1 adipocytes is mediated at posttranscriptional and posttranslational levels. J Biol Chem 264:9030–9038PubMedGoogle Scholar
  37. Semenkovich CF, Luo C-C, Nakanishi MK, Chen S-H, Smith LC, Chan L (1990) In vitro expression and site-specific mutagenesis of the cloned human lipoprotein lipase gene. J Biol Chem 265:5429–5433PubMedGoogle Scholar
  38. Simpson GG (1945) The principles of classification and a classification of mammals. Bull Am Museum Nat Hist 85:1–350Google Scholar
  39. Sparrow JT, Gotto AM Jr (1982) Apolipoprotein/lipid interactions: studies with synthetic polypeptides. CRC Crit Rev Biochem 13:87–107PubMedCrossRefGoogle Scholar
  40. Südhof TC, Russel DW, Goldstein JL, Brown MS, Sanchez-Pescador R, Bell G (1985) Cassette of 8 exons shared by genes for LDL receptor and EGF precursor. Science 228:893–895PubMedCrossRefGoogle Scholar
  41. Verger R (1984) Lipases. Borgström B, Brockman HL (eds), Elsevier, Amsterdam, pp 83–150Google Scholar
  42. Wardell MR, Brennan SO, James ED, Fraser R, Carrell RW (1987) Apolipoprotein E2-Christchurch (136 Arg → Ser): new variant of human apolipoprotein E in a patient with Type III hyperlipoproteinemia. J Clin Invest 80:483–490PubMedCrossRefGoogle Scholar
  43. Wetterau JR, Aggerbeck LP, Rall SC, Weisgraber KH (1988) Human apolipoprotein E3 in aqueous solution. I. Guidance for two structural domains. J Biol Chem 263:6240–6248PubMedGoogle Scholar
  44. Winkler FK, D’Arcy A, Hunziker W (1990) Structure of human pancreatic lipase. Nature 343:771–774PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 1992

Authors and Affiliations

  • L. Chan
  • W. Hide
  • Yau-Wen Yang
  • Wen-Hsiung Li

There are no affiliations available

Personalised recommendations