INHIBITION OF PARAOXONASE1 BY KETONE BODIES: AN INVITRO STUDY

Authors

  • AUSTIN RICHARD S
  • CLETUS J M D’SOUZA

Abstract

Objective: In uncontrolled diabetes mellitus, concentration of ketone bodies is elevated to up to 25mM. This study aims to investigate the inhibitory action of ketone bodies on paraoxonase and arylesterase (ARE'ase) activity of Paraoxonase1 (PON1).

Method: The inhibition of PON1 by ketone bodies was determined spectrophotometrically by using paraoxon and phenyl acetate as substrates.

Result: Acetone decreased 32% of paraoxonase activity and 23% of ARE'ase activity. Sodium-3-hydroxybutyrate showed 20 % reduction in paraoxonase activity but it did not affect ARE'ase activity. In contrast, neither of the enzyme activities was affected by sodium acetoacetate.

Conclusion: Higher concentration of acetone and sodium-3- hydroxybutyrate contribute to the reduction of PON1 activity.

Keywords: Paraoxonase1, Arylesterase, High density lipoprotein, Ketone bodies, Sodium -acetoacetate, Acetone, Sodium-3-Hydroxybutyrate.

Downloads

Download data is not yet available.

References

La Du BN. Human serum paraoxonase/aryesterase. In: Kalow W, editor. Pharmacogenetics of Drug Metabolism. New York: Pergamon Press; 1992.p. 51–91

Mackness MI, Mackness B, Durrington PN, Connelly PW, Hegele RA. Paraoxonases biochemistry, genetics and relationship to plasma lipoproteins. Curr Opin Lipidol 1996;7: 69–76.

Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN. Paraoxonase inhibits high density lipoprotein (HDL) oxidation and preserves its functionsA possible peroxidative role for paraoxonase. J Clin Invest 1998; 101:1581–1590.

Jarvik GP, Rozek LS, Brophy VH, Hatsukami TS, Richter RJ, Schellenberg GD, et al. Paraoxonase (PON1) phenotype is a better predictor of vascular disease than is PON1 192 or PON1 155 genotype. Arterioscler Thromb Vasc Biol 2000; 20: 2441-2447.

Ferre N, Camps J, Cabre M, Paul A, Joven J. Hepatic paraoxonase activity alterations and free radical production in rats with experimental cirrhosis. Metabolism 2001;50(9):997–1000.

Camps J, Marsillach J, Joven J. The paraoxonases: role in human diseases and methodological difficulties in measurement. Crit Rev Clin Lab Sci 2009; 46(2):83-106.

Mackness B, Durrington PN, Abuashia B, Boulton AJM, Mackness MI. Low paraoxonase activity in type II diabetes mellitus complicated by retinopathy. Clin Sci (Lond) 2000;98:355–363.

Abbott CA, Mackness MI, Kumar S, Boulton AJ, Durrington PN. Serum paraoxonase activity, concentration and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. Arterioscler Thromb Vasc Biol 1995; 15:1812–1818.

Adepu R, Ari SM. Influence of structured patient education on therapeutic outcomes in diabetes and hypertensive patients. Asian J Pharm Clin Res 2010; 3 Suppl 3: 174-178.

Najmi A, Nasiruddin M, Khan RA, Haque SF. Therapeutic effect of nigella sativa in patients of poor glycemic control. Asian J Pharm Clin Res 2012; 5 Suppl 3: 224-228.

Redgrave TG, Roberts DCK, West CE. Separation of plasma lipoproteins by density-gradient ultracentrifugation. Anal Biochem 1975; 65: 42-49.

Beltowski J, Wojcicka G, Jamroz A. Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia. Atherosclerosis 2003; 170:21- 29.

La Du BN, Eckerson HW. The polymorphic paraoxonase/arylesterase isozymes of human serum. Fed am soc exp boil j 1984; 43:2338-2341.

Krebs HA, Eggleston LV. Metabolism of acetoacetate in animal tissues. Biochem 1945; 39: 408 - 419.

La Du B N. Structural and funtional diversity of paraoxonase. Nat Med 1996;2:1186-1187.

Watson AD, Berliner JA, Hama SY, La Du BN, Fauli KF, Fogelman AM, et al. Protective effect of high density lipoprotein associated paraoxonase: inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 1995;96:2882-2891.

Aviram M, Rosenblat M, Billecke S, Erogul J, Sorenson R, Bisgaier CL, et al. Human serum paraoxonase (PON1 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Rad Biol Med 1999; 26:892-904.

Aviram M, Hardak E, Vaya J, Mahmood S, Milo S, Hoffman A, et al. Human serum paraoxnase (PON1 1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase like activities. Circlulation 2000;101: 2510-2517.

Jaouad L, Milochevitch C, Khalil A. PON1 paraoxonase activity is reduced during HDL oxidation and is an indicator of HDL antioxidant capacity. Free Radic Res 2003;37:77-83.

Ruiz J, Blanche H, James RW, Blatter Garin MC, Vaise C, Charpeutier G, et al. Gln-Arg 191 polymorphism of paraoxonase and coronary heart disease in type 2 diabetes. Lancet 1995; 346: 869–872. a

Dinesh Puri, editor. Textbook of Medical Biochemistry.3rd Ed. India: Elsevier India Pvt Ltd; 2011.p.215

Janardhan A, Chen J, Crawford PA. Altered Systemic Ketone Body Metabolism in Advanced Heart Failure. Tex Heart Inst J 2011; 38(5): 533–538.

Lommi J, Kupari M, Koskinen P, Naveri H, Leinonen H, Pulkki K, et al. Blood ketone bodies in congestive heart failure. J Am Coll Cardiol 1996; 28:665-672.

Samra ZQ , Shabir S, Rehmat Z, Zaman M, Nazir A, Dar N, et al. Synthesis of Cholesterol-Conjugated Magnetic Nanoparticles for Purification of Human Paraoxonase 1. Appl Biochem Biotechnol 2010; 162:671–686.

Published

01-07-2013

How to Cite

RICHARD S, A., and C. J M D’SOUZA. “INHIBITION OF PARAOXONASE1 BY KETONE BODIES: AN INVITRO STUDY”. Asian Journal of Pharmaceutical and Clinical Research, vol. 6, no. 3, July 2013, pp. 119-21, https://journals.innovareacademics.in/index.php/ajpcr/article/view/128.

Issue

Section

Articles