Karabina, S.-A. P., Lehner, A. N., Frank, E., Parthasarathy, S. and Santanam, N. (2005) Oxidative inactivation of paraoxonase - implications in diabetes mellitus and atherosclerosis. Biochimica et Biophysica Acta (BBA) - General Subjects. 1725(2), pp. 213-221. 0304-4165.
| Item Type: | Article |
|---|---|
| Abstract: | Human serum paraoxonase (PON1) has been implicated to play an important role in cardiovascular disease and diabetes. Studies in the literature indicate that PON1 has two different enzyme activities, i.e., esterase and hydroperoxide reducing activities. The objective of this study was to establish the importance of these two activities and to distinguish between them. As the addition of copper immediately inactivated the enzyme, we used auto-oxidation as the model system. Auto-oxidation of HDL resulted in more than 80% reduction of the esterolytic activity, which was protected by antioxidants, Vitamin E (50%) and PDTC (95%) and completely by 1 M glucose. In contrast, the hydroperoxide reducing activity, using unesterified hydroperoxides remained unaffected with time. We also used pNPHPODE (novel substrate) to establish that hydrolysis might be a prerequisite for the enzyme to act on the esterified hydroperoxide. The results indicated that the hydrolysis of the substrate was inhibited under oxidizing conditions with no reduction of the hydroperoxide. Overall, our findings suggest that protecting the esterolytic activity of PON1 by antioxidants might be important in preserving its action on phospholipid peroxides and a concerted reaction involving the esterolytic and hydroperoxide reducing activities might be suggested for the action of PON1 |
| Uncontrolled Keywords: | Lipid hydroperoxide; High density lipoprotein; Antioxidant; Glucose; Esterase; Low density lipoprotein |
| Subjects: |
Q Science > QP Physiology > QP501 Animal biochemistry > QP514.2 Biochemistry R Medicine > RC Internal medicine > RC666 Diseases of the circulatory (Cardiovascular) system R Medicine > RC Internal medicine > RC660 Diabetes |
| Creators: | Karabina, Sonia-Athina P, Lehner, Alexander N, Frank, Elizabeth, Parthasarathy, Sampath and Santanam, Nalini |
| Faculties, Divisions and Institutes: |
University Faculties, Divisions and Research Centres - OLD > Faculty of Health & Society > Sports, Exercise & Life Sciences University Faculties, Divisions and Research Centres - OLD > Research Centre > Institute of Health and Wellbeing > Ageing Research Centre University Faculties, Divisions and Research Centres - OLD > Research Centre > Institute of Health and Wellbeing > Centre for Physical Activity and Chronic Disease Faculties > Faculty of Health & Society > Sports, Exercise & Life Sciences Research Centres > Centre for Health Sciences and Services Research Centres > Centre for Physical Activity and Life Sciences |
| Date: | 15 September 2005 |
| Date Type: | Publication |
| Page Range: | pp. 213-221 |
| Journal or Publication Title: | Biochimica et Biophysica Acta (BBA) - General Subjects |
| Volume: | 1725 |
| Number: | 2 |
| Language: | English |
| DOI: | https://doi.org/10.1016/j.bbagen.2005.07.005 |
| ISSN: | 0304-4165 |
| Status: | Published / Disseminated |
| Refereed: | Yes |
| Related URLs: | |
| URI: | http://nectar.northampton.ac.uk/id/eprint/7 |
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