Biology, Pathology, and Interfacial Enzymology of Pancreatic Phospholipase A2

  • Reynold Homan
  • Mahendra Kumar Jain


The phospholipase A2 (PLA2) secreied by Ihe exocrine pancreas is one of the earliest known members of a large class of enzymes that catalyze hydrolysis of the ester-bond linking fatty acids to the sn-2 position of glycerophospholipids (Fig. 1). The phospholipase A2 enzyme class has been intensely scrutinized, in large part because the sn-2-spccific deacylation of glycerophospholipids is a critical regulatory step in a variety of metabolic pathways, ranging from digestion and defense mechanisms to cicosanoid synthesis and signal transduction.


Mixed Micelle Chemical Step Triglyceride Lipase Carboxyl Ester Hydrolase Pancreatic Phospholipase 
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  1. Agarwal, N., and Pitchumoni, C. S., 1993, Acute pancreatitis: A multisystem disease, Gastroenterologist. 1:113–128.Google Scholar
  2. Åkesson, B., 1982, Content of phospholipids in human diets studied by the duplicate-portion technique, Br. J. Nutr. 47:223–229.PubMedCrossRefGoogle Scholar
  3. Allen, A., Flemström, G., Garner, A., and Kivilaakso, E., 1993, Gastroduodenal mucosal protection, Physiol Rev. 73:823–857.PubMedGoogle Scholar
  4. Arnesjö, B., Nilsson, Å., Barrowman, J., and Borgström, B., 1969, Intestinal digestion and absorption of cholesterol and lecithin in the human, Scand. J. Gastroenterol. 4:653–665.PubMedCrossRefGoogle Scholar
  5. Banks, P. A., 1998, Acute and chronic pancreatitis, in: Gastrointestinal and Liver Disease, Volume 1 (M. Feldman, B. F. Scharschmidt, and M. H. Sleisenger, eds.), W. B. Saunders Company, Philadelphia, pp. 809–862.Google Scholar
  6. Bayburt, T., Yu, B. Z., Street, I., Ghomashchi, F., Laliberte, F., Perrier, H., Wang, Z., Homan, R., Jain, M. K., and Gelb, M. H., 1995, Continuous, vesicle-based fluorimetric assays of 14- and 85-kDAphospholipase A2, Anal Biochem. 232:7–23.PubMedCrossRefGoogle Scholar
  7. Beaton, H. G., Bennion, C., Connolly, S., Cook, A. R., Gensmantel, N. P., Hallam, C., Hardy, K., Hitchin, B., Jackson, C. G., and Robinson, D. H., 1994, Discovery of new non-phospholipid inhibitors of the secretory phospholipases A2, J. Med. Chem. 37:557–559.PubMedCrossRefGoogle Scholar
  8. Berg, O. G., Yu, B. Z., Rogers, J., and Jain, M. K., 1991, Interfacial catalysis by phospholipase A2: Determination of the interfacial kinetic rate constants, Biochem. 30:7283–7297.CrossRefGoogle Scholar
  9. Berg, O. G., Rogers, J., Yu, B. Z., Yao, J., Romsted, L. S., and Jain, M. K., 1997, Thermodynamic and kinetic basis of interfacial activation: Resolution of binding and allosteric effects on pancreatic phospholipase A2 at zwitterionic interfaces, Biochem. 36:14512–14530.CrossRefGoogle Scholar
  10. Berg, O. G., Cajal, Y., Butterfoss, G. L., Grey, R. L., Alsina, M. A., Yu, B. Z., and Jain, M. K., 1998, Interfacial activation of triglyceride lipase from Thermomyces (Humicola) lanuginosa: Kinetic parameters and a basis for control of the lid, Biochem. 37:6615–6627.CrossRefGoogle Scholar
  11. Borgström, A., Erlanson-Albertsson, C., and Borgström, B., 1993, Human pancreatic proenzymes are activated at different rates in vitro, Scand. J. Gastroenterol. 28:455–459.PubMedCrossRefGoogle Scholar
  12. Borgström, B., 1980, Importance of phospholipids, pancreatic phospholipase A2, and fatty acid for the digestion of dietary fat, Gastroenterol. 78:954–962.Google Scholar
  13. Borgström, B., Dahlqvist, A., Lundh, G., and Sjövall, J., 1957, Studies of intestinal digestion and absorption in the human, J. Clin. Invest. 36:1521–1536.PubMedCrossRefGoogle Scholar
  14. Cajal, Y., Rogers, J., Berg, O. G., and Jain, M. K., 1996, Intermembrane molecular contacts by polymyxin B mediate exchange of phospholipids, Biochem. 35:299–308.CrossRefGoogle Scholar
  15. Cajal, Y., Berg, O. G., and Jain, M. K., 2000, Product accumulation during the lag phase as the basis for the activation of phospholipase A2 on monolayers Langmuir 16:252–257.CrossRefGoogle Scholar
  16. Carey, M. C., Small, D. M., and Bliss, C. M., 1983, Lipid digestion and absorption, Ann. Rev. Physiol. 45:651–677.CrossRefGoogle Scholar
  17. Cha, S. S., Lee, D., Adams, J., Kurdyla, J. T., Jones, C. S., Marshall, L. A., Bolognese, B., Abdel-Meguid, S. S., and Oh, B. H., 1996, High-resolution X-ray crystallography reveals precise binding interactions between human nonpancreatic secreted phospholipase A2 and a highly potent inhibitor (FPL67047XX), J. Med. Chem. 39:3878–3881.PubMedCrossRefGoogle Scholar
  18. Cupillard, L., Koumanov, K., Lazdunski, M., and Lambeau, G., 1997, Cloning, chromosomal mapping, and expression of a novel human secretory phospholipase A2, J. Biol. Chem. 272:15745–15752.PubMedCrossRefGoogle Scholar
  19. Cupillard, L., Mulherkar, R., Gomez, N., Kadam, S., Valentin, E., Lazdunski, M., and Lambeau, G., 1999, Both Group IB and Group IIA secreted phospholipases A2 are natural ligands of the mouse 180-kDA M-type receptor, J. Biol. Chem. 274:7043–7051.Google Scholar
  20. Davidson, F. F., and Dennis, E. A., 1990, Evolutionary relationships and implications for the regulation of phospholipase A2 from snake venom to human secreted forms, J. Mol. Evol. 31:228–238.PubMedCrossRefGoogle Scholar
  21. de Hass, G. H., Dijkman, R., Ransac, S., and Verger, R., 1990, Competitive inhibition of lipolytic enzymes. IV. Structural details of acylamino phospholipid analogues important for the potent inhibitory effects on pancreatic phospholipase A2, Biochim. Biophys. Acta 1046:249–257.CrossRefGoogle Scholar
  22. Dennis, E. A., 1997, The growing phospholipase A2 superfamily of signal transduction enzymes, Trends in Biochem. Sci. 22:1–2.CrossRefGoogle Scholar
  23. Diagne, A., Mitjavila, S., Fauvel, J., Chap, H., and Douste-Blazy, L., 1987, Intestinal absorption of ester and ether glycerophospholipids in guinea pig. Role of phospholipase A2 from brush border membrane, Lipids 22:33–40.PubMedCrossRefGoogle Scholar
  24. Diccianni, M. B., Lilly-Stauderman, M., McLean, L. R., Balasubramaniam, A., and Harmony, J. A. K., 1991, Heparin prevents the binding of phospholipase A2 to phospholipid micelles: Importance of the amino-terminus, Biochem. 30:9090–9097.CrossRefGoogle Scholar
  25. Dijkstra, B. W., Renetseder, R., Kalk, K. H., Hol, W. G. J., and Drenth, J., 1983, Structure of porcine pancreatic phospholipase A2 at 2.6 Å resolution and comparison with bovine phospholipase A2, J. Mol. Biol. 168:163–179.PubMedCrossRefGoogle Scholar
  26. Dua, R., Wu, S. K., and Cho, W., 1995, A structure-function study of bovine pancreatic phospholipase A2 using polymerized mixed liposomes, J. Biol. Chem. 270:263–268.PubMedCrossRefGoogle Scholar
  27. Dupureur, C. M., Yu, B. Z., Jain, M. K., Noel, J. P., Deng, T., Li, Y., Byeon, I. J. L., and Tsai, M. D., 1992a, Phospholipase A2 engineering. Structural and functional roles of highly conserved active site residues tyrosine-52 and tyrosine-73, Biochem. 31:6402–6413.CrossRefGoogle Scholar
  28. Dupureur, C. M., Yu, B. Z., Mamone, J. A., Jain, M. K., and Tsai, M. D., 1992b, Phospholipase A2 engineering. The structural and functional roles of aromaticity and hydrophobicity in the conserved phenylalanine-22 and phenylalanine-106 aromatic sandwich, Biochem. 31:10576–10583.CrossRefGoogle Scholar
  29. Fauvel, J., Bonnefis, M.-J., Chap, H., Thouvenot, J.-P., and Douste-Blazy, L., 1981, Evidence for the lack of classical secretory phospholipase A2 in guinea pig pancreas, Biochim. Biophys. Acta 666:72–79.PubMedCrossRefGoogle Scholar
  30. Fawcus, K., Gorton, V. J., Lucas, M. L., and McEwan, G. T. A., 1997, Stimulation of three distinct guanylate cyclases induces mucosal surface alkalinisation in rat small intestine in vitro, Comp. Biochem. Physiol. 118A:291–295.CrossRefGoogle Scholar
  31. Funakoshi, A., Yamada, Y., Migita, Y., and Wakasugi, H., 1993, Simultaneous determinations of pancreatic phospholipase A2 and prophospholipase A2 in various pancreatic diseases, Dig. Dis. Sci. 38:502–506.PubMedCrossRefGoogle Scholar
  32. Gassama-Diagne, A., Fauvel, J., and Chap, H., 1989, Purification of a new, calcium-independent, high molecular weight phospholipase A2/lysophospholipase (phospholipase B) from guinea pig intestinal brush-border membrane, J. Biol. Chem. 264:9470–9475.PubMedGoogle Scholar
  33. Gelb, M. H., Jain, M. K., and Berg, O. G., 1994, Inhibition of phospholipase A2, FASEB J. 8:916–924.PubMedGoogle Scholar
  34. Gelb, M. H., Jain, M. K., and Berg, O. G., 1997, Principles of inhibition of phospholipase A2 and other interfacial enzymes, in: Phospholipase A 2. Basic and Clinical Aspects in Inflammatory Diseases, (W. Uhl, T. J. Nevalainen, and M. W. Büchler, eds.), Kargel, Basel, pp. 123–129.Google Scholar
  35. Ghomashchi, F., Yu, B. Z., Mihelich, E. D., Jain, M. K., and Gelb, M. H., 1991, Kinetic characterization of phospholipase A2 modified by manoalogue, Biochem. 30:9559–9569.CrossRefGoogle Scholar
  36. Grataroli, R., Charbonnier, M., Léonardi, J., Grimaud, J.-C., Lafont, H., and Nalbone, G., 1987, Phospholipase A2 activity in rat stomach, Arch. Biochem. Biophys. 258:77–84.PubMedCrossRefGoogle Scholar
  37. Hamosh, M., 1990, Lingual and gastric lipases, Nutrition 6:421–428.PubMedGoogle Scholar
  38. Hanasaki, K., Yokota, Y., Ishizaki, J., Itoh, T., and Arita, H., 1997, Resistance to endotoxic shock in phospholipase A2 receptor-deficient mice, J. Biol. Chem. 272:32792–32797.PubMedCrossRefGoogle Scholar
  39. Hernell, O., Staggers, J. E., and Carey, M. C., 1990, Physical-chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 2. Phase analysis and aggregation states of luminal lipids during duodenal fat digestion in healthy adult human beings, Biochem. 29:2041–2056.CrossRefGoogle Scholar
  40. Hirohara, J., Sugatani, J., Okumura, T., Sameshima, Y., and Saito, K., 1988, Properties and localization of phospholipase A2 activity in rat stomach, Biochim. Biophys. Acta 919:231–238.Google Scholar
  41. Homan, R., and Hamelehle, K. L., 1998, Phospholipase A2 relieves phosphatidylcholine inhibition of micellar cholesterol absorption and transport by human intestinal cell line Caco-2, J. Lipid Res. 39:1197–1209.PubMedGoogle Scholar
  42. Homan, R., and Krause, B. R., 1997, Established and emerging strategies for inhibition of cholesterol absorption, Curr. Pharm. Design 3:29–44.Google Scholar
  43. Huang, B., Yu, B. Z., Rogers, J., Byeon, I. J. L., Sekar, K., Chen, X., Sundaralingam, M., Tsai, M. D., and Jain, M. K., 1996, Phospholipase A2 engineering. Deletion of the C-terminus segment changes substrate specificity and uncouples calcium and substrate binding at the zwitterionic interface, Biochem. 35:12164–12174.CrossRefGoogle Scholar
  44. Huhtinen, H. T., Gronroos, J. M., Haapamaki, M. M., and Nevalainen, T. J., 1999, Phospholipases A2 in gastric juice of Helicobacter pylori-positive and negative individuals, Clin. Chem. Lab. Med. 37:61–64.PubMedCrossRefGoogle Scholar
  45. Jain, M. K., and Berg, O. G., 1989, The kinetics of interfacial catalysis by phospholipase A2 and regulation of interfacial activation: hopping versus scooting, Biochim. Biophys. Acta 1002:127–156.PubMedCrossRefGoogle Scholar
  46. Jain, M. K., Rogers, J., Jahagirdar, D. V., Marecek, J. F., and Ramirez, F., 1986, Kinetics of interfacial catalysis by phospholipase A2 in intravesicular scooting mode, and heterodiffusion of anionic zwitterionic vesicles, Biochim. Biophys. Acta 860:435–447.PubMedCrossRefGoogle Scholar
  47. Jain, M. K., Yuan, W., and Gelb, M. H., 1989, Competitive inhibition of phospholipase A2 in vesicles, Biochem. 28:4135–4139.CrossRefGoogle Scholar
  48. Jain, M. K., Tao, W., Rogers, J., Arenson, C., Eibl, H., and Yu, B. Z., 1991a, Active-site-directed specific competitive inhibitors of phospholipase A2: Novel transition-state analogues Biochem. 30:10256–10268.CrossRefGoogle Scholar
  49. Jain, M. K., Yu, B. Z., Rogers, J., Ranadive, G. N., and Berg, O. G., 1991b, Interfacial catalysis by phospholipase A2: Dissociation constants for calcium, substrate, products, and competitive inhibitors, Biochem. 30:7306–7317.CrossRefGoogle Scholar
  50. Jain, M. K., Ghomashchi, G., Yu, B. Z., Bayburt, T., Murphy, D., Houck, D., Brownell, J., Reid, J. C., Solowiej, J. E., Jarrell, R., Sasser, M., and Gelb, M. H., 1992a, Fatty acid amides: Scooting mode-based discovery of tight-binding competitive inhibitors of secreted phospholipases A2, J. Med. Chem. 35:3584–3586.PubMedCrossRefGoogle Scholar
  51. Jain, M. K., Yu, B. Z., Rogers, J., Gelb, M. H., Tsai, M. D., Hendrickson, E. K., and Hendrickson, H. S., 1992b, Interfacial catalysis by phospholipase A2: the rate-limiting step for enzymatic turnover, Biochem. 31:7841–7847.CrossRefGoogle Scholar
  52. Jain, M. K., Yu, B. Z., and Berg, O. G., 1993a, Relationship of interfacial equilibria to interfacial activation of phospholipase A2, Biochem. 32:11319–11329.Google Scholar
  53. Jain, M. K., Rogers, J., Hendrickson, H. S., and Berg, O. G., 1993b, The chemical step is not rate-limiting during the hydrolysis by phospholipase A2 of mixed micelles of phospholipid and detergent, Biochem. 32:8360–8367.CrossRefGoogle Scholar
  54. Jain, M. K., Gelb, M. H., Rogers, J., and Berg, O. G., 1995, Kinetic basis for interfacial catalysis by phospholipase A2, Methods Enzymol. 249:567–614.Google Scholar
  55. Johnson, L. J., Frank, S., Vades, P., Pruzanski, W., Lusis, A. J., and Seilhamer, J. J., 1990, Localization and evolution of two human phospholipase A2genes and two related genetic elements, Adv. Exp. Med. Biol. 275:17–34.PubMedCrossRefGoogle Scholar
  56. Kinoshita, E., Handa, K., Kajiyama, G., and Sugiyama, M., 1997, Activation of MAP kinase cascade induced by human pancreatic phospholipase A2 in a human pancreatic cancer cell line, FEBS Lett. 407:343–346.PubMedCrossRefGoogle Scholar
  57. Kishino, J., Kawamoto, K., Ishizaki, J., Verheij, H. M., Ohara, O., and Arita, H., 1995, Pancreatic-type phospholipase A2 activates prostaglandin E2 production in rat mesangial cells by receptor binding reaction, J. Biochem. 117:420–424.PubMedCrossRefGoogle Scholar
  58. Kortesuo, P. T., Hietaranta, A. J., Jämiä, M., Hirsimäki, P., and Nevalainen, T. J., 1993, Rat pancreatic phospholipase A2, Int. J. Pancreatology 13:111–118.Google Scholar
  59. Kundu, G. C., and Mukherjee, A. B., 1997, Evidence that porcine pancreatic phospholipase A2 via its high affinity receptor stimulates extracellular matrix invasion by normal and cancer cells, V. Biol. Chem. 272:2346–2353.Google Scholar
  60. Lambeau, G., and Lazdunski, M., 1999, Receptors for a growing family of secreted phospholipases A2 Trends Pharmacol. Sct 20:162–170.CrossRefGoogle Scholar
  61. Layer, P., Go, V. L. W., and DiMagno, E. P., 1986, Fate of pancreatic enzymes during small intestinal aboral transit in humans, Am. J. Physiol. 251:G475–G480PubMedGoogle Scholar
  62. LeMaheiu, R. A., Carson, M., Han, R. J., Madison, V. S., Hope, W. C., Chen, T., Morgan, D. W., and Hendrickson, H. S., 1993, N-(Carboxymethyl-N-[3,5-bis(decyloxy)phenyl]glycine (Ro 23-9358): A potent inhibitor of secretory phospholipases A2 with antiinflammatory activity, J. Med. Chem. 36:3029–3031.CrossRefGoogle Scholar
  63. Li, Y., Yu, B. Z., Zhu, H., Jain, M. K., and Tsai, M. D., 1994, Phospholipase A2 engineering. Structural and functional roles of the highly conserved active site residue aspartate-49, Biochem. 33:14714–14722.CrossRefGoogle Scholar
  64. Lindström, M. B., Persson, J., Thurn, L., and Borgström, B., 1991, Effect of pancreatic phospholipase A2and gastric lipase on the action of pancreatic carboxyl ester lipase against lipid substrates in vitro, Biochim. Biophys. Acta 1084:194–197.PubMedCrossRefGoogle Scholar
  65. Li-Stiles, B., Lo, H., and Fischer, S. M., 1998, Identification and characterization of several forms of phospholipase A2 in mouse epidermal keratinocytes, J. Lipid Res. 39:569–582.PubMedGoogle Scholar
  66. Liu, X., Zhu, H., Huang, B., Rogers, J., Yu, B. Z., Kumar, A., Jain, M. K., Sundaralingam, M., and Tsai, M. D., 1995, Phospholipase A2 engineering. Probing the structural and functional roles of N-terminal residues with site-directed mutagenesis, X-ray, and NMR, Biochem. 34:7322–7334.CrossRefGoogle Scholar
  67. Lowe, M. E., 1994, The structure and function of pancreatic enzymes, in: Physiology of the Gastrointestinal Tract, (L. R. Johnson, ed.), Raven Press, New York, pp. 1531–1542.Google Scholar
  68. Mackay, K., Starr, J. R., Lawn, R. M., and Ellsworth, J. L., 1997, Phosphatidylcholine hydrolysis is required for pancreatic cholesterol esterase- and phospholipase A2-facilitated cholesterol uptake into intestinal Caco-2 cells, J. Biol. Chem. 272:13380–13389.PubMedCrossRefGoogle Scholar
  69. Mansbach, C. M., 1977, The origin of chylomicron phosphatidylcholine in the rat, J. Clin. Invest. 60:411–420.PubMedCrossRefGoogle Scholar
  70. Matsuda, Y., Ogawa, M., Shibata, T., Nakaguchi, K., Nishijima, J., Wakasugi, C., and Mori, T., 1987, Distribution of immunoreactive pancreatic phospholipase A2 (IPPL-2) in various human tissues, Res. Commun. Chem. Pathol. Pharmacol 58:281–284.PubMedGoogle Scholar
  71. Nalbone, G., Charbonnier-Augeire, M., Lafont, H., Grataroli, R., Vigne, J. L., Lairon, D., Chabert, C., Leonardi, J., Hauton, J. C., and Verger, R., 1983, Adsorption of pancreatic (pro)phospholipase A2 to various physiological substrates, J. Lipid Res. 24:1441–1450.PubMedGoogle Scholar
  72. Nevalainen, T. J., Hietaranta, A. J., and Gronroos, J. M., 1999, Phospholipase A2 in acute pancreatitis: New biochemical and pathological aspects, Hepatogastroenterology 46:2731–2135.PubMedGoogle Scholar
  73. Ohara, O., Ishizaki, J., and Arita, H., 1995, Structure and function of phospholipase A2 receptor, Prog. Lipid Res. 34:117–138.PubMedCrossRefGoogle Scholar
  74. Pind, S., and Kuksis, A., 1991, Further characterization of a novel phospholipase B (phospholipase A2-lysophospholipase) from intestinal brush-border membranes, Biochem. Cell Biol. 69:346–357.PubMedCrossRefGoogle Scholar
  75. Plebani, M., 1993, Pepsinogens in health and disease, Crit. Rev. Clin. Lab. Sci. 30:273–328.PubMedCrossRefGoogle Scholar
  76. Ramirez, F., and Jain, M. K., 1991, Phospholipase A2 at the bilayer interface, Proteins 9:229–239.PubMedCrossRefGoogle Scholar
  77. Rogers, J., Yu, B. Z., Serves, S. V., Tsivgoulis, G. M., Sotiropoulos, D. N., Ioannou, P. V., and Jain, M. K., 1996, Kinetic basis for the substrate specificity during hydrolysis of phospholipids by secreted phospholipase A2, Biochem. 35:9375–9384.CrossRefGoogle Scholar
  78. Rogers, J., Yu, B. Z., Tsai, M. D., Berg, O. G., and Jain, M. K., 1998, Cationic residues 53 and 56 control the anion-induced interfacial k*cat-activation of pancreatic phospholipase A2, Biochem. 37:9549–9556.CrossRefGoogle Scholar
  79. Roy, C. C., Weber, A. M., Lepage, G., Smith, L., and Levy, E., 1988, Digestive and absorptive phase anomalies associated with the exocrine pancreatic insufficiency of cystic fibrosis, J. Pediatr. Gastroenterol. Nutr. 7:S1–S7PubMedCrossRefGoogle Scholar
  80. Sakai, M., Shichiri, M., Hakamata, H., and Horiuchi, S., 1998, Endocytosed lysophosphatidylcholine, through the scavenger receptor, plays an essential role in oxidized low-density lipoprotein-induced macrophage proliferation, Trends Cardiovasc. Med. 8:119–124.PubMedCrossRefGoogle Scholar
  81. Sakata, T., Nakamura, E., Tsuruta, Y., Tamaki, M., Teraoka, H., Tojo, H., Ono, T., and Okamoto, M., 1989Presence of pancreatic type phospholipase A2 mRNA in rat gastric mucosa and lung, Biochim. Biophys. Acta 1007:124–126.PubMedCrossRefGoogle Scholar
  82. Scheele, G., Bartelt, D., and Bieger, W., 1981, Characterization of human exocrine pancreatic proteins by twodimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis, Gastroenterol. 80:461–473.Google Scholar
  83. Scott, D. L., and Sigler, P. B., 1994, Structure and catalytic mechanism of secretory phospholipases A2, Adv. Protein Chem. 45:53–88.PubMedCrossRefGoogle Scholar
  84. Sekar, K., Eswaramoorthy, S., Jain, M. K., and Sundaralingam, M., 1997a, Crystal structure of the complex of bovine pancreatic phospholipase A2 with the inhibitor l-hexadecyl-3-(trifluoroethyl)-,sn-glycero-2-phospho-methanol, Biochem. 36:14186–14191.CrossRefGoogle Scholar
  85. Sekar, K., Yu, B. Z., Rogers, J., Lutton, J., Liu, X., Chen, X., Tsai, M. D., Jain, M. K., and Sundaralingam, M., 1997b, Phospholipase A2 engineering. Structural and functional roles of the highly conserved active site residue aspartate-99, Biochem. 36:3104–3114.CrossRefGoogle Scholar
  86. Sekar, K., and Sundaralingam, M., 1999, High-resolution refinement of orthorhombic bovine pancreatic phospholipase A2 Acta Crystallogr. D Biol. Crystoallogr. 55:46–50.CrossRefGoogle Scholar
  87. Simons, K., and van Meer, G., 1988, Lipid sorting in epithelial cells, Biochem. 27:6197–6202.CrossRefGoogle Scholar
  88. Snitko, Y., Han, S. K., Lee, B. I., and Cho, W., 1999, Differential interfacial and substrate binding modes of mammalian pancreatic phospholipase A2: A comparison among human, bovine and porcine enzymes, Biochem. 38:7803–7810.CrossRefGoogle Scholar
  89. Sternby, B., Nilsson, Å., Melin, T., and Borgström, B., 1991, Pancreatic lipolytic enzymes in human duodenal contents, Scand. J. Gastroenterol. 26:859–866.PubMedCrossRefGoogle Scholar
  90. Tasumi, H., Tojo, H., Senda, T., Ono, T., Fujita, H., and Okamoto, M., 1990, Immunocytochemical studies on the localization of pancreatic-type phospholipase A2 in rat stomach and pancreas, with special reference to the stomach cells, Histochemistry 94:135–140.PubMedCrossRefGoogle Scholar
  91. Thunnissen, M. M. G. M., Eiso, A. B., Kalk, K. H., Drenth, J., Dijkstra, B. W., Kuipers, O. P., Dijkman, R., de Hass, G. H., and Verheij, H. M., 1990, X-ray structure of phospholipase A2 complexed with a substratederived inhibitor, Nature 347:689–691.PubMedCrossRefGoogle Scholar
  92. Tischfield, J. A., 1997, A reassessment of the low molecular weight phospholipase A2 gene family in mammals, J. Biol. Chem. 272:17247–17250.PubMedCrossRefGoogle Scholar
  93. Tojo, H., Ono, T., and Okamoto, M., 1988a, A pancreatic-type phospholipase A2 in rat gastric mucosa, Biochem. Biophys. Res. Comm. 151:1188–1193.PubMedCrossRefGoogle Scholar
  94. Tojo, H., Ono, T., Kuramitsu, S., Kagamiyama, H., and Okamoto, M., 1988b, A phospholipase A2 in the supernatant fraction of rat spleen, J. Biol. Chem. 263:5724–5731.PubMedGoogle Scholar
  95. Tojo, H., Ying, Z., and Okamoto, M., 1993, Purification and characterization of guinea pig gastric phospholipase A2 of the pancreatic type, Eur. J. Biochem. 215:81–90.PubMedCrossRefGoogle Scholar
  96. Tomoo, K., Yamane, Y., Ishida, T., Fujii, S., Ikeda, K., Iwama, S., Katsumura, S., Sumiya, S., Miyagawa, H., and Kitamura, K., 1997, X-ray crystal structure determination and molecular dynamics simulation of prophospholipase A2 inhibited by amide-type substrate analogues, Biochim. Biophys. Acta 1340:178–186.PubMedCrossRefGoogle Scholar
  97. Tso, P., 1994, Intestinal lipid absorption, in: Physiology of the Gastrointestinal Tract, (L. R. Johnson, ed.), Raven Press, New York, pp. 1867–1908.Google Scholar
  98. Tso, P., and Scobey, M., 1986, The role of phosphatidylcholine in the absorption and transport of dietary fat, in: Fat Absorption, (A. Kuksis, ed.), CRC Press, Boca Raton, pp. 177–195.Google Scholar
  99. Valentin, E., Ghomashchi, F., Gelb, M. H., Lazdunski, M., and Lambeau, G., 1999, On the diversity of secreted phospholipases A2, J. Biol. Chem. 274:31195–31202.PubMedCrossRefGoogle Scholar
  100. van den Berg, B., Tessari, M., De Haas, G. H., Verheij, H. M., Boelens, R., and Kaptein, R., 1995, Solution structure of porcine pancreatic phospholipase A2, EMBO J. 14:4123–4131.PubMedGoogle Scholar
  101. Verger, R., and De Haas, G. H., 1976, Interfacial enzyme kinetics of lipolysis, Annu. Rev. Biophys. Bioeng. 5:77–117.PubMedCrossRefGoogle Scholar
  102. Verheij, H. M., 1995, Structure and mechanism of pancreatic phospholipase A2-A molecular biology approach, in: Phospholipase A 2 in Clinical Inflammation, Molecular Approaches to Pathophysiology, (K. B. Glaser and P. Vadas, eds.), CRC Press, Boca Raton, pp. 3–24.Google Scholar
  103. Verheij, H. M., Slotboom, A. J., and De Haas, G. H., 1981, Structure and function of phospholipase A2, Rev. Physiol. Biochem. Pharmacol. 91:91–203.PubMedGoogle Scholar
  104. Wilbers, K. H., Haest, C. W., von Bentheim, M., and Deuticke, B., 1979, Influence of enzymatic phospholipid cleavage on the permeability of the erythrocyte membrane: I. Transport of non-electrolytes via the lipid domain, Biochim. Biophys. Acta 554:388–399.PubMedCrossRefGoogle Scholar
  105. Wilschut, J. C., Regts, J., and Scherphof, G., 1979, Action of phospholipase A2 on phospholipid vesicles, FEBS Lett. 98:181–186.PubMedCrossRefGoogle Scholar
  106. Wittcoff, H., 1951, The lysophosphatides and lecithinases, Reinhold Publishing Corp., New York.Google Scholar
  107. Ying, Z., Tojo, H., Nonaka, Y., and Okamoto, M., 1993, Cloning and expression of phospholipase A2 from guinea pig gastric mucosa, its induction by carbachol and secretion in vitro, Eur. J. Biochem. 215:91–97.PubMedCrossRefGoogle Scholar
  108. Young, S. C., and Hui, D. Y., 1999, Pancreatic lipase/colipase-mediated triacylglycerol hydrolysis is required for cholesterol transport from lipid emulsions to intestinal cells, Biochem. J. 339:615–620.PubMedCrossRefGoogle Scholar
  109. Yu, B. Z., Berg, O. G., and Jain, M. K., 1993, The divalent cation is obligatory for the binding of ligands to the catalytic site of secreted phospholipase A2, Biochem. 32:6485–6492.CrossRefGoogle Scholar
  110. Yu, B. Z., Rogers, J., Ranadive, G. N., Baker, S., Wilton, D. C., Apitz-Castro, R., and Jain, M. K., 1997a, Gossypol modification of Ala-1 of secreted phospholipase A2: A probe for the kinetic effects of sulfate glycoconjugates, Biochem. 36:12400–12411.CrossRefGoogle Scholar
  111. Yu, B. Z., Ghomashchi, F., Cajal, Y., Annand, R. R., Berg, O. G., Gelb, M. H., and Jain, M. K., 1997b, Use of an imperfect neutral diluent and outer vesicle layer scooting mode hydrolysis to analyze the interfacial kinetics, inhibition, and substrate preferences of bee venom phospholipase A2, Biochem. 36:3870–3881.CrossRefGoogle Scholar
  112. Yu, B. Z., Rogers, J., Nicol, G. R., Theopold, K. H., Seshadri, K., Vishweshwara, S., and Jain, M. K., 1998, Catalytic significance of the specificity of divalent cations as Ks* and kcat* cofactor for secreted phospholipase A2, Biochem. 37:12576–12587.CrossRefGoogle Scholar
  113. Yu, B. Z., Rogers, J., Tsai, M. D., Pidgeon, C., and Jain, M. K., 1999a, Contributions of residues of pancreatic phospholipase A2 to interfacial binding, catalysis, and activation, Biochem. 38:4875–4884.CrossRefGoogle Scholar
  114. Yu, B. Z., Berg, O. G., and Jain, M. K., 1999b, Hydrolysis of monodisperse substrate by phospholipase A2 occurs at vessel walls and air bubbles, Biochem. 38:10449–10456.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Reynold Homan
    • 1
  • Mahendra Kumar Jain
    • 2
  1. 1.Parke-Davis Pharmaceutical Research DivisionCardiovascular TherapeuticsAnn Arbor
  2. 2.Department of Chemistry and BiochemistryUniversity of DelawareNewark

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