Lysine Reacts with Cholesterol Hydroperoxide to Form Secosterol Aldehydes and Lysine-Secosterol Aldehyde Adducts
Two cholesterol secosterol aldehydes, namely, 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol A) and its aldolization product 3β-hydroxy-5β-hydroxy-B-norcholestane-6β-carboxyaldehyde (secosterol B), are highly bioactive compounds which have been detected in human tissues and potentially contribu...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2020/5862645 |
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| author | George Wafula Wanjala Arnold Nola Onyango David Rasugu Abuga John Kamathi Muchuna Calvin Onyango Moses Makayoto |
| author_facet | George Wafula Wanjala Arnold Nola Onyango David Rasugu Abuga John Kamathi Muchuna Calvin Onyango Moses Makayoto |
| author_sort | George Wafula Wanjala |
| collection | DOAJ |
| description | Two cholesterol secosterol aldehydes, namely, 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol A) and its aldolization product 3β-hydroxy-5β-hydroxy-B-norcholestane-6β-carboxyaldehyde (secosterol B), are highly bioactive compounds which have been detected in human tissues and potentially contribute to the development of physiological dysfunctions such as atherosclerosis, Alzheimer’s disease, diabetes, and cancer. They were originally considered to be exclusive products of cholesterol ozonolysis and thus to be evidence for endogenous ozone formation. However, it was recently postulated that primary amines such as lysine may catalyse their formation from cholesterol-5α-hydroperoxide (Ch-5α-OOH), the main product of the oxidation of cholesterol with singlet oxygen. This involves cyclization of Ch-5α-OOH to an unstable dioxetane intermediate, which decomposes to form secosterol aldehydes with triplet carbonyl groups, whose return to the singlet state is at least partly coupled to the conversion of triplet molecular oxygen to singlet oxygen. Here, we subjected cholesterol to photosensitized oxidation, which predominantly produces Ch-5α-OOH and minor amounts of the 6α- and 6β-hydroperoxides, exposed the hydroperoxide mixture to lysine in the presence of the antioxidant 2,6-ditertiary-butyl-4-hydroxytoluene (BHT), and analysed the reaction mixture by liquid chromatography-electrospray ionization-mass spectrometry. Consistent with the postulated lysine-catalysed formation of secosterol aldehydes, we detected formation of the latter and several types of their lysine adducts, including carbinolamines, Schiff’s bases, and amide-type adducts. We propose that the amide type adducts, which are major biomarkers of lipid oxidation, are mainly formed by singlet oxygen-mediated oxidation of the carbinolamine adducts. |
| format | Article |
| id | doaj-art-57966607afe04445af2a7089c9170321 |
| institution | Kabale University |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-57966607afe04445af2a7089c91703212025-02-03T06:06:27ZengWileyJournal of Chemistry2090-90632090-90712020-01-01202010.1155/2020/58626455862645Lysine Reacts with Cholesterol Hydroperoxide to Form Secosterol Aldehydes and Lysine-Secosterol Aldehyde AdductsGeorge Wafula Wanjala0Arnold Nola Onyango1David Rasugu Abuga2John Kamathi Muchuna3Calvin Onyango4Moses Makayoto5School of Food and Nutrition Sciences, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000-00200, Nairobi, KenyaSchool of Food and Nutrition Sciences, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000-00200, Nairobi, KenyaSchool of Food and Nutrition Sciences, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000-00200, Nairobi, KenyaSchool of Food and Nutrition Sciences, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000-00200, Nairobi, KenyaKenya Industrial Research and Development Institute, P.O. Box 30650 (00100), Nairobi, KenyaKenya Industrial Research and Development Institute, P.O. Box 30650 (00100), Nairobi, KenyaTwo cholesterol secosterol aldehydes, namely, 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol A) and its aldolization product 3β-hydroxy-5β-hydroxy-B-norcholestane-6β-carboxyaldehyde (secosterol B), are highly bioactive compounds which have been detected in human tissues and potentially contribute to the development of physiological dysfunctions such as atherosclerosis, Alzheimer’s disease, diabetes, and cancer. They were originally considered to be exclusive products of cholesterol ozonolysis and thus to be evidence for endogenous ozone formation. However, it was recently postulated that primary amines such as lysine may catalyse their formation from cholesterol-5α-hydroperoxide (Ch-5α-OOH), the main product of the oxidation of cholesterol with singlet oxygen. This involves cyclization of Ch-5α-OOH to an unstable dioxetane intermediate, which decomposes to form secosterol aldehydes with triplet carbonyl groups, whose return to the singlet state is at least partly coupled to the conversion of triplet molecular oxygen to singlet oxygen. Here, we subjected cholesterol to photosensitized oxidation, which predominantly produces Ch-5α-OOH and minor amounts of the 6α- and 6β-hydroperoxides, exposed the hydroperoxide mixture to lysine in the presence of the antioxidant 2,6-ditertiary-butyl-4-hydroxytoluene (BHT), and analysed the reaction mixture by liquid chromatography-electrospray ionization-mass spectrometry. Consistent with the postulated lysine-catalysed formation of secosterol aldehydes, we detected formation of the latter and several types of their lysine adducts, including carbinolamines, Schiff’s bases, and amide-type adducts. We propose that the amide type adducts, which are major biomarkers of lipid oxidation, are mainly formed by singlet oxygen-mediated oxidation of the carbinolamine adducts.http://dx.doi.org/10.1155/2020/5862645 |
| spellingShingle | George Wafula Wanjala Arnold Nola Onyango David Rasugu Abuga John Kamathi Muchuna Calvin Onyango Moses Makayoto Lysine Reacts with Cholesterol Hydroperoxide to Form Secosterol Aldehydes and Lysine-Secosterol Aldehyde Adducts Journal of Chemistry |
| title | Lysine Reacts with Cholesterol Hydroperoxide to Form Secosterol Aldehydes and Lysine-Secosterol Aldehyde Adducts |
| title_full | Lysine Reacts with Cholesterol Hydroperoxide to Form Secosterol Aldehydes and Lysine-Secosterol Aldehyde Adducts |
| title_fullStr | Lysine Reacts with Cholesterol Hydroperoxide to Form Secosterol Aldehydes and Lysine-Secosterol Aldehyde Adducts |
| title_full_unstemmed | Lysine Reacts with Cholesterol Hydroperoxide to Form Secosterol Aldehydes and Lysine-Secosterol Aldehyde Adducts |
| title_short | Lysine Reacts with Cholesterol Hydroperoxide to Form Secosterol Aldehydes and Lysine-Secosterol Aldehyde Adducts |
| title_sort | lysine reacts with cholesterol hydroperoxide to form secosterol aldehydes and lysine secosterol aldehyde adducts |
| url | http://dx.doi.org/10.1155/2020/5862645 |
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