![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
KN Gan, A Smolen, HW Eckerson and BN La Du
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
Evidence is presented that human serum contains a single enzyme with both paraoxonase and arylesterase activities. Throughout the steps of purification and after obtaining over 600-fold purification of the enzyme, the arylesterase activity (measured with phenylacetate as the substrate) co-eluted and retained the same ratio of activity to paraoxonase activity as it had in the initial plasma sample. Paraoxon and DFP (diisopropylfluorophosphate) both complete with phenylacetate as substrates; the inhibition is of mixed type with paraoxon and competitive with DFP. Paraoxonase and arylesterase activities require calcium, and both are inhibited to the same degree by EDTA. Purified arylesterase/paraoxonase is a glycoprotein with a minimal molecular weight of about 43,000. It has up to three sugar chains per molecule, and carbohydrate represents about 15.8% of the total weight. The enzyme has an isoelectric point of 5.1. Its amino acid composition shows nothing unusual, except for a relatively high content of leucine. We conclude that human serum arylesterase and paraoxonase activities are catalyzed by a single enzyme, capable of hydrolyzing a broad spectrum of organophosphate substrates and a number of aromatic carboxylic acid esters. Studies on the genetically determined polymorphism responsible for two allozymic forms (A and B) of the esterase are described in the following paper.
This article has been cited by other articles:
|
|
 |
|
  R. C. Stevens, S. M. Suzuki, T. B. Cole, S. S. Park, R. J. Richter, and C. E. Furlong From the Cover: Engineered recombinant human paraoxonase 1 (rHuPON1) purified from Escherichia coli protects against organophosphate poisoning PNAS, September 2, 2008; 105(35): 12780 - 12784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Whorton, B. Jastrzebska, P. S.-H. Park, D. Fotiadis, A. Engel, K. Palczewski, and R. K. Sunahara Efficient Coupling of Transducin to Monomeric Rhodopsin in a Phospholipid Bilayer J. Biol. Chem., February 15, 2008; 283(7): 4387 - 4394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sarandol, S. Kirli, C. Akkaya, N. Ocak, E. Eroz, and E. Sarandol Coronary artery disease risk factors in patients with schizophrenia: effects of short term antipsychotic treatment J Psychopharmacol, November 1, 2007; 21(8): 857 - 863. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Itzhaki, H. Dorchin, G. Clark, L. Lavie, P. Lavie, and G. Pillar The Effects of 1-Year Treatment With a Herbst Mandibular Advancement Splint on Obstructive Sleep Apnea, Oxidative Stress, and Endothelial Function Chest, March 1, 2007; 131(3): 740 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Endo, M. Ban, K. Hirata, A. Yamamoto, Y. Hara, and Y. Momose Involvement of CYP2A6 in the Formation of a Novel Metabolite, 3-Hydroxypilocarpine, from Pilocarpine in Human Liver Microsomes Drug Metab. Dispos., March 1, 2007; 35(3): 476 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Browne, S. T. Koury, S. Marion, G. Wilding, P. Muti, and M. Trevisan Accuracy and Biological Variation of Human Serum Paraoxonase 1 Activity and Polymorphism (Q192R) by Kinetic Enzyme Assay Clin. Chem., February 1, 2007; 53(2): 310 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Roberts, C. Ng, S. Hama, A. J. Eliseo, and R. J. Barnard Effect of a short-term diet and exercise intervention on inflammatory/anti-inflammatory properties of HDL in overweight/obese men with cardiovascular risk factors J Appl Physiol, December 1, 2006; 101(6): 1727 - 1732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. San Millan, F. Alvarez-Blasco, M. Luque-Ramirez, J. I. Botella-Carretero, and H. F. Escobar-Morreale The PON1-108C/T polymorphism, and not the polycystic ovary syndrome, is an important determinant of reduced serum paraoxonase activity in premenopausal women Hum. Reprod., December 1, 2006; 21(12): 3157 - 3161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Gaidukov, M. Rosenblat, M. Aviram, and D. S. Tawfik The 192R/Q polymorphs of serum paraoxonase PON1 differ in HDL binding, lipolactonase stimulation, and cholesterol efflux J. Lipid Res., November 1, 2006; 47(11): 2492 - 2502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vega-Lopez, L. M Ausman, S. M Jalbert, A. T Erkkila, and A. H Lichtenstein Palm and partially hydrogenated soybean oils adversely alter lipoprotein profiles compared with soybean and canola oils in moderately hyperlipidemic subjects Am. J. Clinical Nutrition, July 1, 2006; 84(1): 54 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. L. Stevens, C. Rodriguez, A. L. Pavluck, M. J. Thun, and E. E. Calle Association of Polymorphisms in the Paraoxonase 1 Gene with Breast Cancer Incidence in the CPS-II Nutrition Cohort. Cancer Epidemiol. Biomarkers Prev., June 1, 2006; 15(6): 1226 - 1228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Dursun, E. Demirtas, A. Bayrak, and H. Yarali Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS? Hum. Reprod., January 1, 2006; 21(1): 104 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, W. Chan, S. Wallenstein, G. Berkowitz, and J. G. Wetmur Haplotype-Phenotype Relationships of Paraoxonase-1 Cancer Epidemiol. Biomarkers Prev., March 1, 2005; 14(3): 731 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Teiber, D. I. Draganov, and B. N. La Du Purified human serum PON1 does not protect LDL against oxidation in the in vitro assays initiated with copper or AAPH J. Lipid Res., December 1, 2004; 45(12): 2260 - 2268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Nguyen and D.-E. Sok Preferential inhibition of paraoxonase activity of human paraoxonase 1 by negatively charged lipids J. Lipid Res., December 1, 2004; 45(12): 2211 - 2220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Ribas, J. L. Sanchez-Quesada, R. Anton, M. Camacho, J. Julve, J. C. Escola-Gil, L. Vila, J. Ordonez-Llanos, and F. Blanco-Vaca Human Apolipoprotein A-II Enrichment Displaces Paraoxonase From HDL and Impairs Its Antioxidant Properties: A New Mechanism Linking HDL Protein Composition and Antiatherogenic Potential Circ. Res., October 15, 2004; 95(8): 789 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayek, E. Pavlotzky, S. Hamoud, R. Coleman, S. Keidar, M. Aviram, and M. Kaplan Tissue Angiotensin-Converting-Enzyme (ACE) Deficiency Leads to a Reduction in Oxidative Stress and in Atherosclerosis: Studies in ACE-Knockout Mice Type 2 Arterioscler. Thromb. Vasc. Biol., November 1, 2003; 23(11): 2090 - 2096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rosenblat, D. Draganov, C. E. Watson, C. L. Bisgaier, B. N. La Du, and M. Aviram Mouse Macrophage Paraoxonase 2 Activity Is Increased Whereas Cellular Paraoxonase 3 Activity Is Decreased Under Oxidative Stress Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 468 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Rozenberg, D. M. Shih, and M. Aviram Human Serum Paraoxonase 1 Decreases Macrophage Cholesterol Biosynthesis: Possible Role for Its Phospholipase-A2-Like Activity and Lysophosphatidylcholine Formation Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 461 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Marathe, G. A. Zimmerman, and T. M. McIntyre Platelet-activating Factor Acetylhydrolase, and Not Paraoxonase-1, Is the Oxidized Phospholipid Hydrolase of High Density Lipoprotein Particles J. Biol. Chem., January 31, 2003; 278(6): 3937 - 3947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Shamir, N. Shehadeh, M. Rosenblat, O. Eshach-Adiv, R. Coleman, M. Kaplan, S. Hamoud, S. Lischinsky, and T. Hayek Oral Insulin Supplementation Attenuates Atherosclerosis Progression in Apolipoprotein E-Deficient Mice Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 104 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Freese, G. Alfthan, M. Jauhiainen, S. Basu, I. Erlund, I. Salminen, A. Aro, and M. Mutanen High intakes of vegetables, berries, and apples combined with a high intake of linoleic or oleic acid only slightly affect markers of lipid peroxidation and lipoprotein metabolism in healthy subjects Am. J. Clinical Nutrition, November 1, 2002; 76(5): 950 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Josse, C. Ebel, D. Stroebel, A. Fontaine, F. Borges, A. Echalier, D. Baud, F. Renault, M. le Maire, E. Chabrieres, et al. Oligomeric States of the Detergent-solubilized Human Serum Paraoxonase (PON1) J. Biol. Chem., August 30, 2002; 277(36): 33386 - 33397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Van Lenten, A. C. Wagner, G.M. Anantharamaiah, D. W. Garber, M. C. Fishbein, L. Adhikary, D. P. Nayak, S. Hama, M. Navab, and A. M. Fogelman Influenza Infection Promotes Macrophage Traffic Into Arteries of Mice That Is Prevented by D-4F, an Apolipoprotein A-I Mimetic Peptide Circulation, August 27, 2002; 106(9): 1127 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Boisfer, D. Stengel, D. Pastier, P. M. Laplaud, N. Dousset, E. Ninio, and A.-D. Kalopissis Antioxidant properties of HDL in transgenic mice overexpressing human apolipoprotein A-II J. Lipid Res., May 1, 2002; 43(5): 732 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Ng, G. F. Maguire, J. Wylie, A. Ravandi, W. Xuan, Z. Ahmed, M. Eskandarian, A. Kuksis, and P. W. Connelly Oxidative Stress Is Markedly Elevated in Lecithin:Cholesterol Acyltransferase-deficient Mice and Is Paradoxically Reversed in the Apolipoprotein E Knockout Background in Association with a Reduction in Atherosclerosis J. Biol. Chem., March 29, 2002; 277(14): 11715 - 11720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kaplan, T. Hayek, A. Raz, R. Coleman, L. Dornfeld, J. Vaya, and M. Aviram Pomegranate Juice Supplementation to Atherosclerotic Mice Reduces Macrophage Lipid Peroxidation, Cellular Cholesterol Accumulation and Development of Atherosclerosis J. Nutr., August 1, 2001; 131(8): 2082 - 2089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Brushia, T. M. Forte, M. N. Oda, B. N. La Du, and J. K. Bielicki Baculovirus-mediated expression and purification of human serum paraoxonase 1A J. Lipid Res., June 1, 2001; 42(6): 951 - 958. [Abstract] [Full Text]
|
|
|
|
|
|
B. J. Van Lenten, A. C. Wagner, D. P. Nayak, S. Hama, M. Navab, and A. M. Fogelman High-Density Lipoprotein Loses Its Anti-Inflammatory Properties During Acute Influenza A Infection Circulation, May 8, 2001; 103(18): 2283 - 2288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Billecke, D. Draganov, R. Counsell, P. Stetson, C. Watson, C. Hsu, and B. N. L. Du Human Serum Paraoxonase (pon1) Isozymes Q and R Hydrolyze Lactones and Cyclic Carbonate Esters Drug Metab. Dispos., November 1, 2000; 28(11): 1335 - 1342. [Abstract] [Full Text]
|
|
|
|
|
|
Bart De Geest, D. Stengel, M. Landeloos, M. Lox, L. Le Gat, D. Collen, P. Holvoet, and E. Ninio Effect of Overexpression of Human Apo A-I in C57BL/6 and C57BL/6 Apo E-Deficient Mice on 2 Lipoprotein-Associated Enzymes, Platelet-Activating Factor Acetylhydrolase and Paraoxonase : Comparison of Adenovirus-Mediated Human Apo A-I Gene Transfer and Human Apo A-I Transgenesis Arterioscler. Thromb. Vasc. Biol., October 1, 2000; 20 (10): e68 - e75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Navab, S. Y. Hama, C. J. Cooke, G. M. Anantharamaiah, M. Chaddha, L. Jin, G. Subbanagounder, K. F. Faull, S. T. Reddy, N. E. Miller, et al. Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1 J. Lipid Res., September 1, 2000; 41(9): 1481 - 1494. [Abstract] [Full Text]
|
|
|
|
|
|
M. Navab, S. Y. Hama, G. M. Anantharamaiah, K. Hassan, G. P. Hough, A. D. Watson, S. T. Reddy, A. Sevanian, G. C. Fonarow, and A. M. Fogelman Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3 J. Lipid Res., September 1, 2000; 41(9): 1495 - 1508. [Abstract] [Full Text]
|
|
|
|
|
|
M. Tomas, M. Senti, F. Garcia-Faria, J. Vila, A. Torrents, M. Covas, and J. Marrugat Effect of Simvastatin Therapy on Paraoxonase Activity and Related Lipoproteins in Familial Hypercholesterolemic Patients Arterioscler. Thromb. Vasc. Biol., September 1, 2000; 20(9): 2113 - 2119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kujiraoka, T. Oka, M. Ishihara, T. Egashira, T. Fujioka, E. Saito, S. Saito, N. E. Miller, and H. Hattori A sandwich enzyme-linked immunosorbent assay for human serum paraoxonase concentration J. Lipid Res., August 1, 2000; 41(8): 1358 - 1363. [Abstract] [Full Text]
|
|
|
|
|
|
C. C. Hedrick, K. Hassan, G. P. Hough, J. Yoo, S. Simzar, C. R. Quinto, S.-M. Kim, A. Dooley, S. Langi, S. Y. Hama, et al. Short-Term Feeding of Atherogenic Diet to Mice Results in Reduction of HDL and Paraoxonase That May Be Mediated by an Immune Mechanism Arterioscler. Thromb. Vasc. Biol., August 1, 2000; 20(8): 1946 - 1952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aviram, E. Hardak, J. Vaya, S. Mahmood, S. Milo, A. Hoffman, S. Billicke, D. Draganov, and M. Rosenblat Human Serum Paraoxonases (PON1) Q and R Selectively Decrease Lipid Peroxides in Human Coronary and Carotid Atherosclerotic Lesions : PON1 Esterase and Peroxidase-Like Activities Circulation, May 30, 2000; 101(21): 2510 - 2517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aviram, L. Dornfeld, M. Rosenblat, N. Volkova, M. Kaplan, R. Coleman, T. Hayek, D. Presser, and B. Fuhrman Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice Am. J. Clinical Nutrition, May 1, 2000; 71(5): 1062 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jakubowski Calcium-dependent Human Serum Homocysteine Thiolactone Hydrolase. A PROTECTIVE MECHANISM AGAINST PROTEIN N-HOMOCYSTEINYLATION J. Biol. Chem., February 11, 2000; 275(6): 3957 - 3962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Sorenson, C. L. Bisgaier, M. Aviram, C. Hsu, S. Billecke, and B. N. La Du Human Serum Paraoxonase/Arylesterase's Retained Hydrophobic N-Terminal Leader Sequence Associates With HDLs by Binding Phospholipids : Apolipoprotein A-I Stabilizes Activity Arterioscler. Thromb. Vasc. Biol., September 1, 1999; 19(9): 2214 - 2225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Gowri, D. R. Van der Westhuyzen, S. R. Bridges, and J. W. Anderson Decreased Protection by HDL From Poorly Controlled Type 2 Diabetic Subjects Against LDL Oxidation May Be Due to the Abnormal Composition of HDL Arterioscler. Thromb. Vasc. Biol., September 1, 1999; 19(9): 2226 - 2233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Forte, M. N. Oda, L. Knoff, B. Frei, J. Suh, J. A. K. Harmony, W. D. Stuart, E. M. Rubin, and D. S. Ng Targeted disruption of the murine lecithin:cholesterol acyltransferase gene is associated with reductions in plasma paraoxonase and platelet-activating factor acetylhydrolase activities but not in apolipoprotein J concentration J. Lipid Res., July 1, 1999; 40(7): 1276 - 1283. [Abstract] [Full Text]
|
|
|
|
|
|
B. Ivandic, L. W. Castellani, X.-P. Wang, J.-H. Qiao, M. Mehrabian, M. Navab, A. M. Fogelman, D. S. Grass, M. E. Swanson, M. C. de Beer, et al. Role of Group II Secretory Phospholipase A2 in Atherosclerosis : 1. Increased Atherogenesis and Altered Lipoproteins in Transgenic Mice Expressing Group IIa Phospholipase A2 Arterioscler. Thromb. Vasc. Biol., May 1, 1999; 19(5): 1284 - 1290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Sogorb, I. Sánchez, M. López-Rivadulla, V. Céspedes, and E. Vilanova EDTA-Resistant and Sensitive Phosphotriesterase Activities Associated with Albumin and Lipoproteins in Rabbit Serum Drug Metab. Dispos., January 1, 1999; 27(1): 53 - 59. [Abstract] [Full Text]
|
|
|
|
|
|
H. Cao, A. Girard-Globa, F. Berthezene, and P. Moulin Paraoxonase protection of LDL against peroxidation is independent of its esterase activity towards paraoxon and is unaffected by the Q->R genetic polymorphism J. Lipid Res., January 1, 1999; 40(1): 133 - 139. [Abstract] [Full Text]
|
|
|
|
|
|
M. Aviram, S. Billecke, R. Sorenson, C. Bisgaier, R. Newton, M. Rosenblat, J. Erogul, C. Hsu, C. Dunlop, and B. La Du Paraoxonase Active Site Required for Protection Against LDL Oxidation Involves Its Free Sulfhydryl Group and Is Different From That Required for Its Arylesterase/Paraoxonase Activities : Selective Action of Human Paraoxonase Allozymes Q and R Arterioscler. Thromb. Vasc. Biol., October 1, 1998; 18(10): 1617 - 1624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Pond, H. W. Chambers, C. P. Coyne, and J. E. Chambers Purification of Two Rat Hepatic Proteins with A-Esterase Activity Toward Chlorpyrifos-Oxon and Paraoxon J. Pharmacol. Exp. Ther., September 1, 1998; 286(3): 1404 - 1411. [Abstract] [Full Text]
|
|
|
|
|
|
C.-L. Kuo and B. N. L. Du Calcium Binding by Human and Rabbit Serum Paraoxonases. Structural Stability and Enzymatic Activity Drug Metab. Dispos., July 1, 1998; 26(7): 653 - 660. [Abstract] [Full Text]
|
|
|
|
|
|
K. Tougou, A. Nakamura, S. Watanabe, Y. Okuyama, and A. Morino Paraoxonase Has a Major Role in the Hydrolysis of Prulifloxacin (NM441), a Prodrug of a New Antibacterial Agent Drug Metab. Dispos., April 1, 1998; 26(4): 355 - 359. [Abstract] [Full Text]
|
|
|
|
|
|
B. Garner, A. R. Waldeck, P. K. Witting, K.-A. Rye, and R. Stocker Oxidation of High Density Lipoproteins. II. EVIDENCE FOR DIRECT REDUCTION OF LIPID HYDROPEROXIDES BY METHIONINE RESIDUES OF APOLIPOPROTEINS AI AND AII J. Biol. Chem., March 13, 1998; 273(11): 6088 - 6095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Hasselwander, D. McMaster, D. G. Fogarty, A. P. Maxwell, D. P. Nicholls, and I. S. Young Serum Paraoxonase and Platelet-Activating Factor Acetylhydrolase in Chronic Renal Failure Clin. Chem., January 1, 1998; 44(1): 179 - 181. [Full Text] [PDF]
|
|
|
|
|
|
D. I. Draganov, P. L. Stetson, C. E. Watson, S. S. Billecke, and B. N. La Du Rabbit Serum Paraoxonase 3 (PON3) Is a High Density Lipoprotein-associated Lactonase and Protects Low Density Lipoprotein against Oxidation J. Biol. Chem., October 20, 2000; 275(43): 33435 - 33442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ahmed, A. Ravandi, G. F. Maguire, A. Emili, D. Draganov, B. N. L. Du, A. Kuksis, and P. W. Connelly Apolipoprotein A-I Promotes the Formation of Phosphatidylcholine Core Aldehydes That Are Hydrolyzed by Paraoxonase (PON-1) during High Density Lipoprotein Oxidation with a Peroxynitrite Donor J. Biol. Chem., June 29, 2001; 276(27): 24473 - 24481. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
