Interaction of bile pigments and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with CYP2A6 and CYP2A13 / Nurnadia Majid

Bilirubin and biliverdin are bile pigments produced from the breakdown of senescent red blood cells. Other than mainly known to aid in the digestion of fats, the free radical scavenging property and the inverse relationship between serum bilirubin levels and cancer risk has been widely reported. The...

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Main Author:	Majid, Nurnadia
Format:	Thesis
Language:	English
Published:	2023
Subjects:	QP Physiology
Online Access:	https://ir.uitm.edu.my/id/eprint/88844/1/88844.pdf
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id	my-uitm-ir.88844
record_format	uketd_dc
spelling	my-uitm-ir.888442024-07-22T08:19:52Z Interaction of bile pigments and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with CYP2A6 and CYP2A13 / Nurnadia Majid 2023 Majid, Nurnadia QP Physiology Bilirubin and biliverdin are bile pigments produced from the breakdown of senescent red blood cells. Other than mainly known to aid in the digestion of fats, the free radical scavenging property and the inverse relationship between serum bilirubin levels and cancer risk has been widely reported. The 4-(methylnitrosamino)-1-(3-pyridyl)-1butanone (NNK) is a procarcinogen found in tobacco smoke. Metabolism of NNK mediated by CYP2A6 and CYP2A13 resulted in formation of free radical with DNA damaging property. Inhibitor of NNK metabolism has been of interest to decrease the production of free radicals that contribute to the development of tobacco products induced lung cancer. The interactions of bile pigments with CYP2A6 and CYP2A13 enzymes still largely unknown. Fundamental knowledge on the interaction of bile pigments and NNK with CYP2A6 and CYP2A13 enzymes, is important as part of understanding the protective role of bile pigments in human during NNK-induced carcinogenesis. Therefore, in this study, the interaction of bile pigments with the active site and other possible binding sites in the enzyme structures of CYP2A6 and CYP2A13 was explored. The inhibitory effect of bilirubin and NNK on the coumarin 7hydroxylation mediated by CYP2A6 was also investigated. Molecular docking using AutoDock (ADV) software was performed to computationally dock the bile pigments to the active sites of CYP2A6 and CYP2A13 enzymes. Next, the interactions between the top docked poses of ligands produced by ADV was visualized by PyMOL and PoseView software. Based on the binding energy, NNK exhibited lower binding energy to active sites of CYP2A6 compared to bile pigments, but bile pigments exhibited lower binding energy to CYP2A13 active sites than NNK. Nevertheless, the ligands were found interacted with key amino acid residues at the active sites of CYP2A6 and CYP2A13 crystal structures. DoGSiteScorer was used to predict allosteric sites of both enzymes. 2023 Thesis https://ir.uitm.edu.my/id/eprint/88844/ https://ir.uitm.edu.my/id/eprint/88844/1/88844.pdf text en public masters Universiti Teknologi MARA (UiTM) Faculty of Pharmacy Ramli, Salfarina
institution	Universiti Teknologi MARA
collection	UiTM Institutional Repository
language	English
advisor	Ramli, Salfarina
topic	QP Physiology
spellingShingle	QP Physiology Majid, Nurnadia Interaction of bile pigments and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with CYP2A6 and CYP2A13 / Nurnadia Majid
description	Bilirubin and biliverdin are bile pigments produced from the breakdown of senescent red blood cells. Other than mainly known to aid in the digestion of fats, the free radical scavenging property and the inverse relationship between serum bilirubin levels and cancer risk has been widely reported. The 4-(methylnitrosamino)-1-(3-pyridyl)-1butanone (NNK) is a procarcinogen found in tobacco smoke. Metabolism of NNK mediated by CYP2A6 and CYP2A13 resulted in formation of free radical with DNA damaging property. Inhibitor of NNK metabolism has been of interest to decrease the production of free radicals that contribute to the development of tobacco products induced lung cancer. The interactions of bile pigments with CYP2A6 and CYP2A13 enzymes still largely unknown. Fundamental knowledge on the interaction of bile pigments and NNK with CYP2A6 and CYP2A13 enzymes, is important as part of understanding the protective role of bile pigments in human during NNK-induced carcinogenesis. Therefore, in this study, the interaction of bile pigments with the active site and other possible binding sites in the enzyme structures of CYP2A6 and CYP2A13 was explored. The inhibitory effect of bilirubin and NNK on the coumarin 7hydroxylation mediated by CYP2A6 was also investigated. Molecular docking using AutoDock (ADV) software was performed to computationally dock the bile pigments to the active sites of CYP2A6 and CYP2A13 enzymes. Next, the interactions between the top docked poses of ligands produced by ADV was visualized by PyMOL and PoseView software. Based on the binding energy, NNK exhibited lower binding energy to active sites of CYP2A6 compared to bile pigments, but bile pigments exhibited lower binding energy to CYP2A13 active sites than NNK. Nevertheless, the ligands were found interacted with key amino acid residues at the active sites of CYP2A6 and CYP2A13 crystal structures. DoGSiteScorer was used to predict allosteric sites of both enzymes.
format	Thesis
qualification_level	Master's degree
author	Majid, Nurnadia
author_facet	Majid, Nurnadia
author_sort	Majid, Nurnadia
title	Interaction of bile pigments and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with CYP2A6 and CYP2A13 / Nurnadia Majid
title_short	Interaction of bile pigments and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with CYP2A6 and CYP2A13 / Nurnadia Majid
title_full	Interaction of bile pigments and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with CYP2A6 and CYP2A13 / Nurnadia Majid
title_fullStr	Interaction of bile pigments and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with CYP2A6 and CYP2A13 / Nurnadia Majid
title_full_unstemmed	Interaction of bile pigments and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with CYP2A6 and CYP2A13 / Nurnadia Majid
title_sort	interaction of bile pigments and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (nnk) with cyp2a6 and cyp2a13 / nurnadia majid
granting_institution	Universiti Teknologi MARA (UiTM)
granting_department	Faculty of Pharmacy
publishDate	2023
url	https://ir.uitm.edu.my/id/eprint/88844/1/88844.pdf
_version_	1811768731296071680

Interaction of bile pigments and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with CYP2A6 and CYP2A13 / Nurnadia Majid

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