Annie Borgne-Sanchez, PhD CEO-CSO
|
|
- Elizabeth Atkins
- 8 years ago
- Views:
Transcription
1 Annie Borgne-Sanchez, PhD CEO-CSO Combinaison de tests sur mitochondries isolées et cellules HepaRG pour la prédiction des risques d hépatotoxicité chez l homme Hôpital Robert Debré- 48, Bd Sérurier Paris Parc Biocitech - 102, Av Gaston Roussel Romainville
2 Propidium iodide Propidium iodide Innovative screening platforms MiToxView Predictive toxicity assays MitoPathway Efficacy assays on tumor mitochondria (Bcl-2 antagonists, RC inhibitors ) AnnexinV-fitc MitoXpert Mitochondrial targeting and protection assays (mptp, MitoK-ATP, OS) AnnexinV-fitc 2
3 Drug-induced Mitochondrial Injuries Swelling & Dy m Loss FAO Inhibition Cyto c Release MMP ATP Production mtdna Quantification RC Complex Activity (COX, F0-F1 ATPase) Respiratory Chain Activity ROS Production From Begriche et al. J. Hepatol. (2011) Mitochondrial dysfunctions = key mechanism of hepatotoxicity (DILI)
4 Assays require high quality mitochondria Isolating Pure, Functional and Stable Mitochondria Whatever the Source Rodent organs Liver Heart Kidney Brain Isolated mouse liver mitochondria Purity: 95% Integrity: >90% Functional PTP: swelling with Ca 2+ Functional PTP: Ca 2+ + CsA Respiratory control index (4,2) Human cell lines HepaRG Wi-38 HT-29 PC3 Jurkat HepG2 Purity: 95% Integrity: >90% Isolated tumor mitochondria Functional PTP: swelling with Ca 2+ Functional PTP: Ca 2+ + CsA Respiratory control index (2,5)
5 Screening assays on isolated mitochondria Process to detect acute and direct compound mitochondrial toxicity Compound Predicting Drug-induced Organo-toxicity Rodent organs or Cell lines Isolated mitochondria Isolated & Functional Mitochondria Multiparametric assays (Spectrofluorimetry) in Human 200 compounds on 5 parameters / week Small molecules, peptides, recombinant proteins, natural extracts
6 O.D. RFU Cyto c (%) RFU Membrane Integrity & Functionality First stage screening to assess compound toxicity Membrane Integrity Functionality + Time (min.) Time (min.) Time (min.) Swelling Dy DY m loss Cyt. c release Oxygen consumption Complex (CI, CII) I & II Membranes permeabilization Proton flow alteration Outer membrane permeabilization Apoptosis marker Respiratory chain function Ctrl 100% : Calcium ClCCP Alamethicin Rotenone Oligomycin A
7 Additional Functional Parameters Second stage screening to assess compound toxicity Fatty acid b-oxidation ROS production ATP production Lipid metabolism (Subtrate: palmitoyl L carnitine) Oxidative stress (superoxide anion O 2 ) Metabolic activity 100% Ctrl : Rotenone Antimycin A Antimycin A 7
8 Respiratory chain complex activity Complex I (NADH quinone oxidoreductase) Complex II (succinate deshydrogenase) Complex III (coenzyme Q - cytochrome c oxidoreductase) Complex IV (cytochrome c oxidase) Complex V (F0-F1 ATP synthase) O.D 550nm Cox activity (KCN) 8
9 High Predictivity Demonstrated on 124 Compounds
10 DILI Prediction Study Design 124 Drugs 87 Hepatotoxic drugs 37 Non-Hepatotoxic Drugs Screening of mitochondrial dysfunction with multiparametric assays on isolated mouse liver mitochondria: swelling, membrane potential, cytochrome c release, respiration (CI and CII) 2 Cut-off: EC x Cmax variability, liver, multiple doses (Xu et al., 2008) EC µm MitochondrioToxic drug when: EC20 cut-off for at least 1 parameter Non MitochondrioToxic drug when: EC20 > cut-off for the 5 parameters
11 Examples of Dose-response Alpidem Diclofenac Perhexiline Troglitazone
12 Correlation with DILI & Mechanisms of Toxicity in vitro mitochondrial toxicity Compound Therapeutic Swelling DY m loss Cyto c O 2 cons CII O 2 cons CI Human class EC 20 µm EC 20 µm EC 20 µm EC 20 µm EC 20 µm hepatotoxicity Amantadine Anti-viral >800 >200 >400 >400 >400 N Amiodarone Anti-arythmic ND 2.6 < ND Y Clotrimazole Anti-fungal ND 23.9 > ND Y Diclofenac NSAID > > Y Gentamicin Antibiotic > >200 >200 ND Y Ketoconazole Anti-fungal > >400 > Y Lumiracoxib NSAID > > Y Manganese chloride Nutritive agent >800 >800 >800 >400 >400 N Methyldopa Antihypertensive >400 >400 ND > Y Molsidomine Anti-anginal >400 >400 >400 >200 >200 N Perhexiline Anti-anginal < Y Saquinavir Antiretroviral ND 10.3 > * 30.4* Y Sucrose Anti-asthenic >800 >800 >800 >800 >800 N Sulindac NSAID >200 >200 >200 > Y Tamoxifen Anti-cancer ND ND Y Tramadol Analgesic > >400 > * N Porceddu M, Buron N, Roussel C, Labbe G, Fromenty B and Borgne-Sanchez A. Prediction of Liver Injury induced by chemicals in Human with a Multiparametric Assay on Isolated Mouse Liver Mitochondria. Toxicol. Sci Positive predictive value >82% (p<0.001) Sensitivity: 92%
13 Detection of hepatotoxicity risks using HepaRG mitochondria Isolated HepaRG mitochondria HepaRG = hepatocyte-like cells Metabolic performances of primary hepatocytes Indefinite growth capacity of hepatic cell lines Purity: 95% Integrity: >90% Functional PTP: swelling with Ca 2+ Functional PTP: Ca 2+ + CsA High respiratory control index Suitable for screening Transmembrane potential O2 consumption (CII)
14 Detection of Hepatotoxicity using HepaRG Cells Assays on HepaRG treated cells for detection of: - long term mitochondrio-toxicity - metabolites mitochondrio-toxicity Dose-response and time-course (2, 7, 12 days) Cell viability Transmembrane potential ADP/ATP ratio mtros and global ROS production Global cellular respiration Quantification of mtdna (qpcr) Long term effects of AZT and ddc (12 days treatment)
15 Summary Multiparametric study on isolated mitochondria combined with time-courses on HepaRG differentiated cells allows identification of compounds with: Direct and acute mitochondrial toxicity of the parent drug Isolated Mito HepaRG 2d HepaRG 7d HepaRG 12d Cpd 1 Direct mitochondrial toxicity of a metabolite Isolated Mito HepaRG 2d HepaRG 7d HepaRG 12d Cpd 2 Direct but long term mitochondrial toxicity (mtdna) Isolated Mito HepaRG 2d HepaRG 7d HepaRG 12d Cpd 3 Cytotoxic effect with downstream mitochondrial damages Isolated Mito HepaRG 2d HepaRG 7d HepaRG 12d Cpd 4 no apparent mitochondrial toxicity : Moderate effect : Strong effect
16 Mitologics SAS Robert Debre Hospital 48, Bd Serurier Paris France Annie BORGNE-SANCHEZ, PhD For further information, visit our web site
Chapter 19a Oxidative Phosphorylation and Photophosphorylation. Multiple Choice Questions
Chapter 19a Oxidative Phosphorylation and Photophosphorylation Multiple Choice Questions 1. Electron-transfer reactions in mitochondria Page: 707 Difficulty: 1 Ans: E Almost all of the oxygen (O 2 ) one
More informationOxidative Phosphorylation
Oxidative Phosphorylation NADH from Glycolysis must be transported into the mitochondrion to be oxidized by the respiratory electron transport chain. Only the electrons from NADH are transported, these
More informationSeahorse XF Cell Mito Stress Test Kit
Seahorse XF Cell Mito Stress Test Kit Part # 103015-100 User Guide For use with Seahorse XF e and XF Extracellular Flux Analyzers For Research Use Only 1 Table of Contents Product Description... 2 Introduction...
More informationBiochemistry of cellular organelles
Kontinkangas, L101A Biochemistry of cellular organelles Lectures: 1. Membrane channels; 2. Membrane transporters; 3. Soluble lipid/metabolite-transfer proteins; 4. Mitochondria as cellular organelles;
More informationChem 306 Chapter 21 Bioenergetics Lecture Outline III
Chem 306 Chapter 21 Bioenergetics Lecture Outline III I. HOW IS ATP GENERATED IN THE FINAL STAGE CATABOLISM? A. OVERVIEW 1. At the end of the citric acid cycle, all six carbons of glucose have been oxidized
More informationThe Physiology of Hyperbaric Oxygen Therapy. Free Radicals and Reactive Oxygen Species. I. Introduction Definition, Source, function and Purpose
The Physiology of Hyperbaric Oxygen Therapy Free Radicals and Reactive Oxygen Species I. Introduction Definition, Source, function and Purpose A. Definition of free radicals and reactive oxygen species
More informationEnergy Production In A Cell (Chapter 25 Metabolism)
Energy Production In A Cell (Chapter 25 Metabolism) Large food molecules contain a lot of potential energy in the form of chemical bonds but it requires a lot of work to liberate the energy. Cells need
More information12 Tra. Seahorse XF Stress Test Report Generator User Guide. Seahorse XF Stress Test Report Generator. User Guide
12 Tra Seahorse XF Stress Test Report Generator User Guide Seahorse XF Stress Test Report Generator User Guide Table of Contents Introduction... 3 Assay Parameter Calculations... 3 Preparing Assay Result
More informationThe correct answer is d C. Answer c is incorrect. Reliance on the energy produced by others is a characteristic of heterotrophs.
1. An autotroph is an organism that a. extracts energy from organic sources b. converts energy from sunlight into chemical energy c. relies on the energy produced by other organisms as an energy source
More informationElectron transport chain, oxidative phosphorylation & mitochondrial transport systems. Joško Ivica
Electron transport chain, oxidative phosphorylation & mitochondrial transport systems Joško Ivica Electron transport chain & oxidative phosphorylation collects e - & -H Oxidation of foodstuffs oxidizes
More informationElectron Transport and Oxidative Phosphorylation
CHM333 LECTURES 37 & 38: 4/27 29/13 SPRING 2013 Professor Christine Hrycyna Electron Transport and Oxidative Phosphorylation Final stages of aerobic oxidation of biomolecules in eukaryotes occur in the
More informationChapter 16 The Citric Acid Cycle
Chapter 16 The Citric Acid Cycle Multiple Choice Questions 1. Which of the following is not true of the reaction catalyzed by the pyruvate dehydrogenase complex? A) Biotin participates in the decarboxylation.
More informationCellular Respiration Stage 4: Electron Transport Chain
Cellular Respiration Stage 4: Electron Transport Chain 2006-2007 Cellular respiration What s the point? The point is to make ATP! ATP ATP accounting so far Glycolysis 2 ATP Kreb s cycle 2 ATP Life takes
More informationChapter 9 Mitochondrial Structure and Function
Chapter 9 Mitochondrial Structure and Function 1 2 3 Structure and function Oxidative phosphorylation and ATP Synthesis Peroxisome Overview 2 Mitochondria have characteristic morphologies despite variable
More information1. Explain the difference between fermentation and cellular respiration.
: Harvesting Chemical Energy Name Period Overview: Before getting involved with the details of cellular respiration and photosynthesis, take a second to look at the big picture. Photosynthesis and cellular
More informationAP BIOLOGY CHAPTER 7 Cellular Respiration Outline
AP BIOLOGY CHAPTER 7 Cellular Respiration Outline I. How cells get energy. A. Cellular Respiration 1. Cellular respiration includes the various metabolic pathways that break down carbohydrates and other
More informationChapter 8. Summary and Perspectives
Chapter 8 Summary and Perspectives 131 Chapter 8 Summary Overexpression of the multidrug resistance protein MRP1 confer multidrug resistance (MDR) to cancer cells. The contents of this thesis describe
More informationThe amount of cellular adenine is constant. -It exists as either ATP, ADP, or AMP (the concentration of these vary)
Electron transport chain Final stage of aerobic oxidation! Also known as: -oxidative phosphorylation(when coupled to ATP synthase) -respiration (when coupled to ATP synthase) Purpose: -Recycle reduced
More informationSteatosis Colorimetric Assay Kit
Steatosis Colorimetric Assay Kit Item No. 10012643 www.caymanchem.com Customer Service 800.364.9897 Technical Support 888.526.5351 1180 E. Ellsworth Rd Ann Arbor, MI USA TABLE OF CONTENTS GENERAL INFORMATION
More informationLactic Acid Dehydrogenase
Lactic Acid Dehydrogenase Pyruvic Acid Dehydrogenase Complex Pyruvate to ACETYL coa CC CoA + CO 2 Mitochondria 3 carbon Pyruvate to 2 carbon ACETYL Coenzyme A Pyruvate Acetyl CoA + CO 2 + NADH + H + CO2
More informationBIOMARKERS AND TOXICITY MECHANISMS 06 Mechanisms Metabolism & Detoxification. Luděk Bláha, PřF MU, RECETOX www.recetox.cz
BIOMARKERS AND TOXICITY MECHANISMS 06 Mechanisms Metabolism & Detoxification Luděk Bláha, PřF MU, RECETOX www.recetox.cz Metabolism and detoxification Chemicals enter body... mostly via food Pass directly
More informationIncorporation of a Novel 3D Cell Culture System to Perform in vitro Cytotoxicity Analyses using Human Primary Hepatocytes
A p p l i c a t i o n N o t e Incorporation of a Novel 3D Cell Culture System to Perform in vitro Cytotoxicity Analyses using Human Primary Hepatocytes Brad Larson, Senior Scientist, Applications Department,
More informationBottlenecks in Clinical Source Material Acquisition. Aby J. Mathew, PhD May 5, 2009 ISCT Annual Meeting San Diego, CA amathew@biolifesolutions.
Bottlenecks in Clinical Source Material Acquisition Aby J. Mathew, PhD May 5, 2009 ISCT Annual Meeting San Diego, CA amathew@biolifesolutions.com Biopreservation What s the issue? Biopreservation considerations
More informationCellular Respiration and Fermentation
LECTURE PRESENTATIONS For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson Chapter 9 Cellular Respiration and Fermentation
More informationChapter 7 Active Reading Guide Cellular Respiration and Fermentation
Name: AP Biology Mr. Croft Chapter 7 Active Reading Guide Cellular Respiration and Fermentation Overview: Before getting involved with the details of cellular respiration and photosynthesis, take a second
More informationSummary of Metabolism. Mechanism of Enzyme Action
Summary of Metabolism Mechanism of Enzyme Action 1. The substrate contacts the active site 2. The enzyme-substrate complex is formed. 3. The substrate molecule is altered (atoms are rearranged, or the
More informationStudent name ID # 2. (4 pts) What is the terminal electron acceptor in respiration? In photosynthesis? O2, NADP+
1. Membrane transport. A. (4 pts) What ion couples primary and secondary active transport in animal cells? What ion serves the same function in plant cells? Na+, H+ 2. (4 pts) What is the terminal electron
More informationBasic Overview of Preclinical Toxicology Animal Models
Basic Overview of Preclinical Toxicology Animal Models Charles D. Hebert, Ph.D., D.A.B.T. December 5, 2013 Outline Background In Vitro Toxicology In Vivo Toxicology Animal Models What is Toxicology? Background
More informationChapter 9 Cellular Respiration
Chapter 9 Cellular Respiration Electrons carried in NADH Mitochondrion Glucose Glycolysis Pyruvic acid Krebs Cycle Electrons carried in NADH and FADH 2 Electron Transport Chain Cytoplasm Mitochondrion
More informationAnabolic and Catabolic Reactions are Linked by ATP in Living Organisms
Chapter 5: Microbial Metabolism Microbial Metabolism Metabolism refers to all chemical reactions that occur within a living a living organism. These chemical reactions are generally of two types: Catabolic:
More informationCell Injury, Adaptation and Death
Harvard-MIT Division of Health Sciences and Technology HST.035: Principle and Practice of Human Pathology Dr. Badizadegan Cell Injury, Adaptation and Death HST.035 Spring 2003 Overview of Cell Injury Cells
More informationWhat affects an enzyme s activity? General environmental factors, such as temperature and ph. Chemicals that specifically influence the enzyme.
CH s 8-9 Respiration & Metabolism Metabolism A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction. An enzyme is a catalytic protein. Hydrolysis of sucrose by
More information21.8 The Citric Acid Cycle
21.8 The Citric Acid Cycle The carbon atoms from the first two stages of catabolism are carried into the third stage as acetyl groups bonded to coenzyme A. Like the phosphoryl groups in ATP molecules,
More informationElectron Transport System. May 16, 2014 Hagop Atamian hatamian@ucdavis.edu
Electron Transport System May 16, 2014 Hagop Atamian hatamian@ucdavis.edu What did We learn so far? Glucose is converted to pyruvate in glycolysis. The process generates two ATPs. Pyruvate is taken into
More informationMetabolism Poster Questions
Metabolism Poster Questions Answer the following questions concerning respiration. 1. Consider the mitochondrial electron transport chain. a. How many hydrogen ions can be pumped for every NADH? b. How
More informationNursing 113. Pharmacology Principles
Nursing 113 Pharmacology Principles 1. The study of how drugs enter the body, reach the site of action, and are removed from the body is called a. pharmacotherapeutics b. pharmacology c. pharmacodynamics
More informationTHE ELECTRON TRANSPORT CHAIN. Oxidative phosphorylation
THE ELECTRON TRANSPORT CHAIN Oxidative phosphorylation Overview of Metabolism Mitochondria Structure -Schematic Mitochondria Structure -Photomicrograph Overview of ETC Impermiable to ions Permiable via
More informationChapter 14- RESPIRATION IN PLANTS
Chapter 14- RESPIRATION IN PLANTS Living cells require a continuous supply of energy for maintaining various life activities. This energy is obtained by oxidizing the organic compounds (carbohydrates,
More informationChapter 7 Cellular Respiration
Phases of aerobic cellular respiration 1. Glycolysis 2. Transition or Acetyl-CoA reaction 3. Krebs cycle 4. Electron transport system Chapter 7 Cellular Respiration These phases are nothing more than metabolic
More information- Oxygen is needed for cellular respiration [OVERHEAD, fig. 6.2, p. 90 / 4th: 6.1] - lungs provide oxygen to blood, blood brings oxygen to the cells.
Cellular respiration - how cells make energy - Oxygen is needed for cellular respiration [OVERHEAD, fig. 6.2, p. 90 / 4th: 6.1] - ATP - this is provided by the lungs - lungs provide oxygen to blood, blood
More informationPhotosystems I and II
Photosystems I and II March 17, 2003 Bryant Miles Within the thylakoid membranes of the chloroplast, are two photosystems. Photosystem I optimally absorbs photons of a wavelength of 700 nm. Photosystem
More informationChapter 8: Energy and Metabolism
Chapter 8: Energy and Metabolism 1. Discuss energy conversions and the 1 st and 2 nd law of thermodynamics. Be sure to use the terms work, potential energy, kinetic energy, and entropy. 2. What are Joules
More informationRole Of Mitochondria In Mesenchymal Stem Cells
Role Of Mitochondria In Mesenchymal Stem Cells Roman Eliseev, MD, PhD, Tamara Raymond, Regis O'Keefe, MD, PhD. University of Rochester, Rochester, NY, USA. Disclosures: R. Eliseev: None. T. Raymond: None.
More informationThe diagram below summarizes the effects of the compounds that cells use to regulate their own metabolism.
Regulation of carbohydrate metabolism Intracellular metabolic regulators Each of the control point steps in the carbohydrate metabolic pathways in effect regulates itself by responding to molecules that
More informationChapter 3 The respiratory electron transport chain
6 Chapter 3 The respiratory electron transport chain In this chapter, I will describe function and location of the native cytochrome b (Cb) in the mitochondrial electron transport chain. In the frame of
More informationFigure 5. Energy of activation with and without an enzyme.
Biology 20 Laboratory ENZYMES & CELLULAR RESPIRATION OBJECTIVE To be able to list the general characteristics of enzymes. To study the effects of enzymes on the rate of chemical reactions. To demonstrate
More informationApplication Note No. 2 / July 2012. Quantitative Assessment of Cell Quality, Viability and Proliferation. System
Application Note No. 2 / July 2012 Quantitative Assessment of Cell Quality, Viability and Proliferation System Quantitative Assessment of Cell Quality, Viability and Proliferation Introduction In vitro
More informationIs ATP worth the investment?
Is ATP worth the investment? ATP (adenosine tri-phosphate) can be thought of as the currency of the cell. Most cellular metabolic processes cost a certain amount of ATP in order to happen. Furthermore,
More informationDo mitochondria play a role in ME/CFS?
Do mitochondria play a role in ME/CFS? Karl Morten Nuffield Dept of Obstetrics & Gynaecology University of Oxford ME/CFS Awareness Week May 10 th 2016 Mitochondrial dysfunction associates with many chronic
More informationAAGPs TM Anti-Aging Glyco Peptides. Enhancing Cell, Tissue and Organ Integrity Molecular and biological attributes of lead AAGP molecule
AAGPs TM Anti-Aging Glyco Peptides Enhancing Cell, Tissue and Organ Integrity Molecular and biological attributes of lead AAGP molecule 1 Acknowledgements This presentation was prepared by Dr. Samer Hussein
More informationPantesin Effective support for heart healthy cholesterol levels*
Pantesin Effective support for heart healthy cholesterol levels* { Pantesin Effective support for heart healthy cholesterol levels* Many health-conscious adults keeping a watchful eye on their cholesterol
More informationPhotosynthesis takes place in three stages:
Photosynthesis takes place in three stages: Light-dependent reactions Light-independent reactions The Calvin cycle 1. Capturing energy from sunlight 2. Using energy to make ATP and NADPH 3. Using ATP and
More informationRESPIRATION AND FERMENTATION: AEROBIC AND ANAEROBIC OXIDATION OF ORGANIC MOLECULES. Bio 171 Week 6
RESPIRATION AND FERMENTATION: AEROBIC AND ANAEROBIC OXIDATION OF ORGANIC MOLECULES Bio 171 Week 6 Procedure Label test tubes well, including group name 1) Add solutions listed to small test tubes 2) For
More informationATP accounting so far ELECTRON TRANSPORT CHAIN & CHEMIOSMOSIS. The Essence of ETC: The Electron Transport Chain O 2
accounting so far The final stage of cellular respiration: ELECTRON TRANSPORT CHAIN & CHEMIOSMOSIS Glycolysis 2 Kreb s cycle 2 Life takes a lot of energy to run, need to extract more energy than 4! There
More informationMitigation Strategies for Reactive Intermediates in
Mitigation Strategies for Reactive Intermediates in Drug Discovery ew Perspectives in DMPK: Informing Drug Discovery Royal Society of Chemistry, London February 10-11, 2014 Thomas A. Baillie School of
More informationOxygen Metabolism and Oxygen Toxicity
xygen Metabolism and xygen Toxicity February 26, 2003 Bryant Miles Chemiosmotic Theory Chemiosomitic Theory state that the free energy of electron transport is coupled to the pumping of protons from the
More informationElectron Transport and Oxidative Phosphorylation. The Mitochondrion. Electron Transport. Oxidative Phosphorylation. Control of ATP Production
Electron Transport and Oxidative Phosphorylation The Mitochondrion Electron Transport Oxidative Phosphorylation Control of ATP Production C 6 H 12 O 6 + 6O 2 6CO 2 + 6H 2 O G ' = -2823 kj. mol -1 C 6 H
More informationName: Hour: Elements & Macromolecules in Organisms
Name: Hour: Elements & Macromolecules in Organisms Most common elements in living things are carbon, hydrogen, nitrogen, and oxygen. These four elements constitute about 95% of your body weight. All compounds
More informationCopyright 2000-2003 Mark Brandt, Ph.D. 54
Pyruvate Oxidation Overview of pyruvate metabolism Pyruvate can be produced in a variety of ways. It is an end product of glycolysis, and can be derived from lactate taken up from the environment (or,
More informationAnimal Cell Culture. Third Edition. A Practical Approach OXJORD VNIVVRSITY 1'RVSS
Animal Cell Culture Third Edition A Practical Approach Edited by John R. W. Masters 3rd Floor Research Laboratories, University College London OXJORD VNIVVRSITY 1'RVSS Contents List of protocols page xiii
More informationSyllabus Chemistry 431B Biochemistry Winter 2013. Course Prerequisite: Grade of C- or better in Biochemistry I (Chem 431A)
Syllabus Chemistry 431B Biochemistry Winter 2013 Instructor: Jamil Momand, Ph.D. Class location and time: Salazar Hall, C-265 MWF 11:40-12:30 Office Hours: La Kretz Hall, Room 270 M 10-11, T 10-11 Email:
More informationThe Need for a PARP in vivo Pharmacodynamic Assay
The Need for a PARP in vivo Pharmacodynamic Assay Jay George, Ph.D., Chief Scientific Officer, Trevigen, Inc., Gaithersburg, MD For further infomation, please contact: William Booth, Ph.D. Tel: +44 (0)1235
More informationCellular Respiration & Metabolism. Metabolism. Coupled Reactions: Bioenergetics. Cellular Respiration: ATP is the cell s rechargable battery
Cellular Respiration & Metabolism Metabolic Pathways: a summary Metabolism Bioenergetics Flow of energy in living systems obeys: 1 st law of thermodynamics: Energy can be transformed, but it cannot be
More informationTodays Outline. Metabolism. Why do cells need energy? How do cells acquire energy? Metabolism. Concepts & Processes. The cells capacity to:
and Work Metabolic Pathways Enzymes Features Factors Affecting Enzyme Activity Membrane Transport Diffusion Osmosis Passive Transport Active Transport Bulk Transport Todays Outline -Releasing Pathways
More informationFighting the Battles: Conducting a Clinical Assay
Fighting the Battles: Conducting a Clinical Assay 6 Vocabulary: In Vitro: studies in biology that are conducted using components of an organism that have been isolated from their usual biological surroundings
More informationIn Vivo and In Vitro Screening for Thyroid Hormone Disruptors
In Vivo and In Vitro Screening for Thyroid Hormone Disruptors Kevin M. Crofton National lhealth and Environmental Research Laboratory California Environmental Protection Agency Human Health Hazard Indicators
More information2.1.2 Characterization of antiviral effect of cytokine expression on HBV replication in transduced mouse hepatocytes line
i 1 INTRODUCTION 1.1 Human Hepatitis B virus (HBV) 1 1.1.1 Pathogenesis of Hepatitis B 1 1.1.2 Genome organization of HBV 3 1.1.3 Structure of HBV virion 5 1.1.4 HBV life cycle 5 1.1.5 Experimental models
More informationElectron Transport Generates a Proton Gradient Across the Membrane
Electron Transport Generates a Proton Gradient Across the Membrane Each of respiratory enzyme complexes couples the energy released by electron transfer across it to an uptake of protons from water in
More informationIs Exercise the Best Antioxidant Supplement? Len Kravitz, Ph.D.
Is Exercise the Best Antioxidant Supplement? Len Kravitz, Ph.D. As an unexpected consequence of the metabolic steps that convert food into energy, the body produces molecules commonly called free radicals.
More informationBCOR 011 Exam 2, 2004
BCOR 011 Exam 2, 2004 Name: Section: MULTIPLE CHOICE. Choose the one alternative that best completes the statement or answers the question. 1. According to the first law of thermodynamics, A. the universe
More informationAnaerobic and Aerobic Training Adaptations. Chapters 5 & 6
Anaerobic and Aerobic Training Adaptations Chapters 5 & 6 Adaptations to Training Chronic exercise provides stimulus for the systems of the body to change Systems will adapt according to level, intensity,
More informationSOME Important Points About Cellular Energetics by Dr. Ty C.M. Hoffman
SOME Important Points About Cellular Energetics by Dr. Ty C.M. Hoffman An Introduction to Metabolism Most biochemical processes occur as biochemical pathways, each individual reaction of which is catalyzed
More informationAP Bio Photosynthesis & Respiration
AP Bio Photosynthesis & Respiration Multiple Choice Identify the letter of the choice that best completes the statement or answers the question. 1. What is the term used for the metabolic pathway in which
More informationMethods of Grading S/N Style of grading Percentage Score 1 Attendance, class work and assignment 10 2 Test 20 3 Examination 70 Total 100
COURSE: MIB 303 Microbial Physiology and Metabolism (3 Units- Compulsory) Course Duration: Three hours per week for 15 weeks (45 hours). Lecturer: Jimoh, S.O. B.Sc., M.Sc, Ph.D Microbiology (ABU, Zaria)
More informationThe Electron Transport Chain
The Electron Transport hain February 19, 2003 Bryant Miles The citric acid cycle oxidizes acetate into two molecules of 2 while capturing the electrons in the form of 3 NAD molecules and one molecule of
More informationIII. Metabolism Oxidative Phosphorylation
Department of Chemistry and Biochemistry University of Lethbridge Biochemistry 3020 III. Metabolism Oxidative Phosphorylation Biochemical Anatomy of Mitochondria Transmembrane channels allow small molecules
More informationCreatine Kinase Activity Colorimetric Assay Kit ABE5487 100 assays; Store at -20 C
Creatine Kinase Activity Colorimetric Assay Kit ABE5487 100 assays; Store at -20 C I. Introduction: Creatine Kinase (CK) also known as creatine phosphokinase (CPK) and ATP: creatine N- phosphotransferase
More informationHarvesting Energy: Glycolysis and Cellular Respiration. Chapter 8
Harvesting Energy: Glycolysis and Cellular Respiration Chapter 8 Overview of Glucose Breakdown The overall equation for the complete breakdown of glucose is: C 6 H 12 O 6 + 6O 2 6CO 2 + 6H 2 O + ATP The
More informationCytotoxic and Biotherapies Credentialing Programme Module 2
Cytotoxic and Biotherapies Credentialing Programme Module 2 1. The Cell Cycle 2. Cancer Therapies 3. Adjunctive Therapies On completion of this module the RN will State the difference between a normal
More informationUnit 5 Photosynthesis and Cellular Respiration
Unit 5 Photosynthesis and Cellular Respiration Advanced Concepts What is the abbreviated name of this molecule? What is its purpose? What are the three parts of this molecule? Label each part with the
More informationBiology 20 Cellular Respiration Review NG Know the process of Cellular Respiration (use this picture if it helps):
Biology 20 Cellular Respiration Review NG Know the process of Cellular Respiration (use this picture if it helps): 1) How many ATP molecules are produced for each glucose molecule used in fermentation?
More informationCellular Respiration An Overview
Why? Cellular Respiration An Overview What are the phases of cellular respiration? All cells need energy all the time, and their primary source of energy is ATP. The methods cells use to make ATP vary
More informationHow To Treat The Sando Syndrome
Consultation on Drugs for Rare Diseases Rare Disease Day Symposium Hannover Medical School (MHH), Solidarity Rare but Strong Together Roland Seifert, MHH @ Dear Sir, I am writing hoping that there might
More information1. The diagram below represents a biological process
1. The diagram below represents a biological process 5. The chart below indicates the elements contained in four different molecules and the number of atoms of each element in those molecules. Which set
More information1. Enzymes. Biochemical Reactions. Chapter 5: Microbial Metabolism. 1. Enzymes. 2. ATP Production. 3. Autotrophic Processes
Chapter 5: Microbial Metabolism 1. Enzymes 2. ATP Production 3. Autotrophic Processes 1. Enzymes Biochemical Reactions All living cells depend on biochemical reactions to maintain homeostasis. All of the
More informationBiological importance of metabolites. Safety and efficacy aspects
Biological importance of metabolites Safety and efficacy aspects Bernard Walther Technologie Servier Biological importance of metabolites Safety testing of drug metabolites Bioanalytical strategy Structural
More informationCompartmentalization of the Cell. Objectives. Recommended Reading. Professor Alfred Cuschieri. Department of Anatomy University of Malta
Compartmentalization of the Cell Professor Alfred Cuschieri Department of Anatomy University of Malta Objectives By the end of this session the student should be able to: 1. Identify the different organelles
More informationReactive Oxygen Species Production by Forward and Reverse Electron Fluxes in the Mitochondrial Respiratory Chain
Reactive Oxygen Species Production by Forward and Reverse Electron Fluxes in the Mitochondrial Respiratory Chain Vitaly A. Selivanov 1,2, Tatyana V. Votyakova 3 *, Violetta N. Pivtoraiko 4, Jennifer Zeak
More informationElements & Macromolecules in Organisms
Name: Date: Per: Table # Elements & Macromolecules in rganisms Most common elements in living things are carbon, hydrogen, nitrogen, and oxygen. These four elements constitute about 95% of your body weight.
More informationClassical drug resistance in the molecular age
Classical drug resistance in the molecular age Robert O Connor, Ph.D. Senior Programme Leader, Translational Cancer Pharmacology Lecturer in Biological Sciences, School of Nursing Chair ICORG Translational
More informationWilliam Shaw, Ph.D. The Great Plains Laboratory, Inc., Lenexa, Kansas, USA
Inhibition of dopamine conversion to norepinephrine by Clostridia metabolites appears to be a (the) major cause of autism, schizophrenia, and other neuropsychiatric disorders. All these factors can now
More informationHP8 herbal formula selectively inhibits prostate cancer cell line proliferation by inducing G2/M cell cycle arrest.
HP8 herbal formula selectively inhibits prostate cancer cell line proliferation by inducing G2/M cell cycle arrest. Flowers A, Banbury L, Leach D and Waterman P. Centre for Phytochemistry and Pharmacology,
More informationAnatomy and Physiology Placement Exam 2 Practice with Answers at End!
Anatomy and Physiology Placement Exam 2 Practice with Answers at End! General Chemical Principles 1. bonds are characterized by the sharing of electrons between the participating atoms. a. hydrogen b.
More information* Is chemical energy potential or kinetic energy? The position of what is storing energy?
Biology 1406 Exam 2 - Metabolism Chs. 5, 6 and 7 energy - capacity to do work 5.10 kinetic energy - energy of motion : light, electrical, thermal, mechanical potential energy - energy of position or stored
More informationTeriflunomide is the active metabolite of Leflunomide, a drug employed since 1994 for the treatment of rheumatoid arthritis (Baselt, 2011).
Page 1 of 10 ANALYTE NAME AND STRUCTURE TERIFLUNOMIDE Teriflunomide TRADE NAME Aubagio CATEGORY Antimetabolite TEST CODE PURPOSE Therapeutic Drug Monitoring GENERAL RELEVANCY BACKGROUND sclerosis. The
More informationAP BIOLOGY 2015 SCORING GUIDELINES
AP BIOLOGY 2015 SCORING GUIDELINES Question 2 Figure 1. Glycolysis and pyruvate oxidation Figure 2. Krebs cycle Figure 3. Electron transport chain Cellular respiration includes the metabolic pathways of
More informationCytotoxicity and Apoptosis Produced by Cytochrome P450 2E1 in Hep G2 Cells
0026-895X/98/040638-11$3.00/0 Copyright by The American Society for Pharmacology and Experimental Therapeutics All rights of reproduction in any form reserved. MOLECULAR PHARMACOLOGY, 53:638 648 (1998).
More informationRegulation of the Citric Acid Cycle
Regulation of the itric Acid ycle I. hanges in Free Energy February 17, 2003 Bryant Miles kj/mol 40 20 0 20 40 60 80 Reaction DGo' DG TA Free Energy hanges 1 2 3 4 5 6 7 8 9 1.) itrate Synthase 2.) Aconitase
More informationMULTIPLE CHOICE. Choose the one alternative that best completes the statement or answers the question.
Ch23_PT MULTIPLE CHOICE. Choose the one alternative that best completes the statement or answers the question. 1) All of the following statements concerning digestion are correct except A) The major physical
More information