Aldo-Keto Reductases and Toxicant Metabolism

Edited by Trevor M. Penning and J. Mark Petrash

Aldo-Keto Reductases and Toxicant Metabolism

Edited by Trevor M. Penning and J. Mark Petrash

Description

Aldo-Keto Reductases and Toxicant Metabolism provides an overview of the rapidly growing Aldo-Keto Reductase (AKR) superfamily and its role in the metabolism of endogenous and exogenous toxicants. This book discusses the ability of AKRs to metabolize endogenous toxicants including: sugar aldehydes, advanced glycosylation end products, and lipid aldehydes (products of lipid peroxidation decomposition).

The relevance to diabetic complications is also stressed. The role of AKRs to metabolize exogenous toxicants including tobacco carcinogens (tobacco specific nitrosamine ketones and trans-dihydrodiols derived from polycyclic aromatic hydrocarbons), mycotoxins (aflatoxin dialdehydes), and unnatural aldehydes is covered in detail. In the case of PAH trans-dihydrodiols, a clear example is given that AKRs may not always be chemoprotective; in this instance, reactive and redox-active quinones are formed. What emerges is that AKRs play a central role in toxicant metabolism.

Aldo-Keto Reductases and Toxicant Metabolism shows how evolutionary AKRs are conserved in prokaryotes through eukaroytes and can thus be considered primordial genes. They are also regulated by primordial stress signals (osmotic stress, reactive oxygen species, and electrophiles) to respond to toxic insult. The role of AKRs to respond to stress in vivo is given in a model of myocardial ischemia and re-perfusion injury. The power of functional yeast genomics is described to generate AKR null yeast strains and a resultant phenotype.

Aldo-Keto Reductases and Toxicant Metabolism

Edited by Trevor M. Penning and J. Mark Petrash

ACS Symposium Series

Section 1: General Overview
1:Introduction and Overview of the Aldo-Keto Reductase (AKR) Superfamily, Trevor M. Penning
Section 2: AKRs and Endogenous Toxicants
2:Aldo-Keto Reductase-Catalyzed Detoxication of Endogenous Aldehydes Associated With Diabetic Complications, David L. Vander Jagt, Lucy A. Hunsaker, Brian S. Young, and William M. Brown
3:Aldose Reductase Detoxifies Lipid Aldehydes and Their Glutathione Conjugates, Satish K. Srivastava, Kota V. Ramana, Sanjay Srivastava, and Aruni Bhatnagar
4:Role of Aldose Reductase in the Detoxification of Oxidized Phospholipids, Sanjay Srivastava, Kota V. Ramana, Satish K. Srivastava, Stanley E. D'Souza, and Aruni Bhatnagar
Section 3: AKRs and Exogenous Toxicants: Tobacco Related Carcinogens
5:Competing Roles of Reductases in the Detoxification of the Tobacco-Specific Nitrosamine Ketone NNK, Edmund Maser and Ursula Breyer-Pfaff
6:Aldo-Keto Reductases and the Metabolic Activation of Polycyclic Aromatic Hydrocarbons, Trevor M. Penning, Nisha T. Palackal, Seon-Hwa Lee, Ian Blair, Deshan Yu, Jesse A. Berlin, Jeffrey Field, and Ronald G. Harvey
7:Molecular Cloning and Characterization of Dihydrodiol Dehydrogenase from Mouse, Yoshihiro Deyashiki, Takahiro Takatsuji, and Akira Hara
8:Efficient Synthesis of the Active Metabolites of Carcinogenic Polycyclic Aromatic Hydrocarbons, Ronald G. Harvey, Quin Dai, Chongzaho Ran, and Trevor M. Penning
9:Chemistry of PAH o-Quinones Generated by the AKR Pathway of PAH Activation, Sridhar R. Gopishetty, Ronald G. Harvey, Seon-Hwa Lee, Ian A. Blair, and Trevor M. Penning
10:Analysis of Etheno-2'-Deoxyguanosine Adducts as Dosimeters of AKR Mediated Oxidative Stress, Seon-Hwa Lee and Ian A. Blair
Section 4: AKRs and Exogenous Toxicants: Mycotoxins, Aldehydes and Ketones
11:Aflatoxin Aldehyde Reductases, Vincent P. Kelly, Tania O'Connor, Elizabeth M. Ellis, Linda S. Ireland, Cara M. Slattery, Philip J. Sherratt, Dorothy H. Crouch, Christopher Cavin, Benoft Schilter, Andrea Gallina, and John D. Hayes
12:Competing Reactions of Aflatoxin B1-Dialdehyde: Enzymatic Reduction vs Adduction with Lysine, F. Peter Guengerich, Kevin M. Williams, Thomas R. Sutter, John D. Hayes, William W. Johnson, Kyle O. Arneson, Markus Voehler, Zhenwu Deng, and Thomas M. Harris
13:The use of mammalian cell lines to investigate the role of aldo-keto reductases in the detoxication of aldehydes and ketones, Rachel Gardner, Shubana Kazi, and Elizabeth Ellis
Section 5: AKRs, the Stress Response and Cell Signaling
14:Aldose Reductase and the Stress Response, Aruni Bhatnagar, Si-Qi Liu, Sanjay Srivastava, Kota V. Ramana, and Satish K. Srivastava
15:Aldose Reductase Regulates Reactive Oxygen Species Mediated-Inflammatory Signals, Kota V. Ramana, Deepak Chandra, Sanjay Srivastava, Aruni Bhatangar, and Barat Aggarwal
16:Aldo-Keto Reductases in the Stress Response of the Budding Yeast Saccharomyces cerevisiae, Qing Chang, Theresa Harter, Terry Griest, B.S.N. Murthy and J. Mark Petrash

Aldo-Keto Reductases and Toxicant Metabolism

Edited by Trevor M. Penning and J. Mark Petrash

ACS Symposium Series

Author Information

Edited by Trevor M. Penning, Professor of Pharmacology, Biochemistry, & Biophysics; Associate Dean of Postdoctoral Research Training, University of Pennsylvania School of Medicine, and J. Mark Petrash, Professor and Director of Research, Washington University School of Medicine