UDP-Glucuronosyltransferases (UGTs): Overview

Size: px
Start display at page:

Download "UDP-Glucuronosyltransferases (UGTs): Overview"

Transcription

1 UDP-Glucuronosyltransferases (UGTs): Overview Anna Radominska-Pandya Department of Biochemistry and Molecular Biology University of Arkansas for Medical Sciences Little Rock, Arkansas, US October 2010; Gdansk University of Technology

2 General Concept of Detoxification Endobiotics Xenobiotics Metabolism Inactive Excretion Products Urine Bile Phase I Oxidation (P450s) OH Phase II Conjugation (UGTs) HO HO COOH O OH H O Lipid Soluble Water Soluble

3 Biotransformation of Drugs and Endobiotics via Oxidation and Conjugation Pathways Phase 0: Absorption of Drugs and Endobiotics Phase I: Oxidation CYP450s Warfarin HO Phase II: Conjugation UGTs SULTs GSTs Phase III: Excretion to Bile and Urine Glucuronic Acid O 7-OH-warfarin glucuronide Abbreviations: CYP450 (Cytochrome P450); UGT (UDP-Glucuronosyltransferase); SULT (Sulfotransferase); GST (Glutathione Sulfatransferase)

4 Biotransformation via Glucuronidation Lipophilic Substrates UGT Therapeutic Drugs Carcinogens Environmental Toxins Dietary Constituents Bilirubin Steroids Bile Acids Retinoic Acids Fatty Acids Prostaglandins UDP-GlcUA Co-Substrate Cytoplasm _ COO - Lumen + H3 N _ ER Various Glucuronides Electophilic Glucuronides Acyl glucuronides (NSAIDs) N-O-glucuronides (Hydroxamic Acids) Hydrophilic β-d-glucuronides Bioactivated Glucuronides Retinoic Acid-gluc 6-O-Morphine-gluc 3-O-Lithocholic Acid-gluc D-ring glucuronides of estradiol, testosterone, DHEA

5 Substrate Specificity of UGTs Substrate specificity is broad and overlapping (promiscuous) Wide range of substrates: Phenols Endogenous substrates Xenobiotic substrates Drugs Dietary plant constituents Billirubin Carcinogens Bile acids Amines Types of glucuronides: Coumarins O-glucuronides Opioids Including acyl glucuronides Steroids N-glucuronides S-glucuronides C-glucuronides Simple Complex Aliphatic alcohols Anthraquinones/flavones Carboxylic acids Sapogenins Primary Secondary Tertiary Heterocyclic Estrogens Androgens Progestin Bile acids Tukey R.H

6 Glucuronidation Reactions Catalyzed by UGTs O-Glucuronidation N-Glucuronidation S-Glucuronidation C-Glucuronidation

7 UDP-Glucuronosyltransferases (UGTs) Large family of membrane bound glycosylated proteins located in the ER as well as inner and outer nuclear membranes Conjugate a wide range of endobiotics and xenobiotics with glucuronic acid Glucuronic acid moiety can attach via a hydroxyl, carboxyl, amino, thiol or carbonyl group on the substrates Generate more polar, water soluble metabolites which can be excreted in urine and bile

8 Biological Significance of Glucuronidation Detoxification increases hydrophobic properties soluble in blood/urine structure different from parent compound no favorable interaction with pharmacological target Detoxification leads to: Excretion of catabolic products Elimination of nucleophilic metabolites of carcinogens Inactivation of biologically active components AZT

9 Biological Significance of Glucuronidation Bioactivation of the parent compound Increases toxicity Increases pharmacological properties Metabolic activation leads to: Cholestatic glucuronides Lithocholic acid glucuronide Estradiol glucuronide Chemically reactive glucuronides: Acyl-glucuronides NSAID glucuronides Ketoprofen Zomepirax Metabolically-active glucuronides Morphine-6-O-glucuronide Irinotecan glucuronide Retinoid glucuronides

10 Biological Significance of Glucuronidation Control of homeostasis of the body and cells Control of steady state concentrations of ligands for nuclear receptors and signaling molecules Downregulation of UGTs results in pathological conditions such as: Cancer Alzheimer s Disease Hyperbiliruminemia Crigler-Najjar syndrome Obesity Other Alteration in Glucuronidation can be caused by: Genetic defects Polymorphisms Tissue-specific regulation

11 Elimination More undesired effects Elimination Elimination Increased toxicity and/or immunological reactions Detoxification Increased potency Detoxification Detoxification Increased potency Activation Toxins and Pollutants Olfactory Substances Drugs XENOBIOTICS UGTs ENDOBIOTICS Ligands for nuclear receptors Bilirubin, Steroids, etc Regulation of gene expression Detoxification Up/down regulation of Protein expression Elimination

12 Phylogenetic Tree of Mammalian UGTs Divergence of 49 mammalian UGT proteins Known mammalian UGTs have been separated into two families, UGT1 and UGT2. UGT1 family is localized on chromosome 2q37 and is divided into 2 subfamilies, UGT1A and UGT1B. UGT2 is localized on chromosome 4q13 and is divided into 3 subfamilies, UGT2A, UGT2B, and UGT2C (not shown). 20 human UGTs have been identified Guillemette C, DMR 2009

13 Guillemette C, DMR 2009

14 UGT1A Gene Cluster and Putative Protein Structure in Humans Ritter JK, 1992 Signal peptide Variable N-terminal domain amino acids Conserved C-terminal domain amino acids Transmembrane fragment UDP- NH 2 Substrates UDP-GlcUA COO - Substrate binding domain UDP-GlcUA binding domain Retention signal Radominska-Pandya A, 1999

15 Hypothetical Model of UGT Topology UDP-GT N + H 3 lumen Transmembrane fragment UDP- GlcUA binding domain Substrate binding domain ER cytosol COO - UGT UDP Gluc-O Lumen HO Transporter Cytosol UDP-GlcUA?? Gluc-O

16 Tissue-Specific Expression of Human UGTs Isoform UGT1A1 Protein Expression Biliary tissue, colon, intestine, liver, stomach, Tissue mrna expression Kidney, trachea, adrenal gland, lung, prostate, testis, thymus, thyroid UGT1A3 UGT1A4 UGT1A6 UGT1A7 UGT1A8 UGT1A9 UGT1A10 UGT2B4 UGT2B7 Biliary tissue, colon, liver, stomach, brain Biliary tissue, colon, liver, intestine, lung, Biliary tissue, colon, liver, stomach, brain, kidney, larynx, lung Orolaryngeal tissue, esophagus, stomach Colon, esophagus, intestine, kidney, larynx Breast, colon, esophagus, liver, kidney, ovary, prostate, skin, testis Orolaryngeal tissue, colon, biliary tissue, esophagus, intestine, stomach Adipose tissue, adrenals, breast, ovary, liver, lung, placenta, prostate, skin, testis, kidney Breast, brain, colon, esophagus, intestine, kidney, liver, lung, and pancreas Adrenal gland, placenta, prostate, salivary gland, small intestine, testis, thymus, thyroid gland, trachea, uterus. Breast Testis, uterus UGT2B10 Liver Adrenal gland, colon, heart, skeletal muscle, testis, uterus UGT2B11 UGT2B15 UGT2B17 Lung Breast, testis, uterus, prostate, lung, ovary, esophagus, kidney, liver, skin Liver, prostate Colon, pancreas, small intestine, stomach, testis, trachea Adrenal gland, bone marrow, brain, colon, lung, pancreas, peripheral leukocytes, salivary gland, small intestine, spinal cord, spleen, stomach, testis, thymus, trachea UGT2A1 Lung Trachea

17 UGT Polymorphisms and Genetic Deficiencies

18 Examples of UGT Polymorphisms UGT1A1 UGT1A1*28 A common variant [A(TA)7TAA] in the TATA-box region of the UGT1A1 promoter UGT1A1*1 Results in: Decrease level of UGT1A1 gene expression Increased breast cancer risk (due to estrogen metabolism), specifically in African American women UGT1A6 Metabolizes aspirin and other NSAIDs Two missense mutations leading to T181A and R184S amino acid substitution UGT1A6*2 Has a frequency of 30% in Caucasian pop. Positively modified protective effect of aspirin (decreased glucuronidation leads to higher levels of aspirin)

19 Examples of UGT Polymorphisms UGT1A7 Glucuronidates polycyclic aromatic hydrocarbons and dietary heterocyclic aromatic amines Three missense mutations in exon 1 result in four alleles: UGT1A7*1 (N129, R131, W208) UGT1A7*2 (K129, K131, W208) UGT1A7*3 (K129, K131, R208) Increased risk of orolaryngeal, liver, and colon cancer UGT1A7*4 (N129, R131, R208) Increased risk of orolaryngeal, liver, and colon cancer UGT2B7 Single nucleotide polymorphisms in coding and regulatory region of UGT2B7 gene are thought to play a role in morphine glucuronidation Cytosine to thymine polymorphism at 802 bp UGT2B7*1 (Y268) 3 times more likely Asian pop than 2B7*2. UGT2B7*2 (H268)

20 Genetic Deficiencies of UGT1A1 Crigler-Najjar disease: Severe, chronic, non-hemolytic, unconjugated hyperbilirubinemia Defect in the gene encoding bilirubin UGT1A1 Caused by mutations to common exons 2-5 or by a mutation to exon 1 Type I Complete loss of bilirubin-conjugating activity Type II Partial loss of bilirubin-conjugating activity (typically <10% of normal) Responds to phenobarbital treatment Gilbert s syndrome: Mild, unconjugated hyperbilirubinemia Defect in the gene encoding bilirubin UGT1A1 Missense mutation in the coding region Homozygous insertion into promoter

21 Conclusions

22 Practice Questions

BIOMARKERS 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 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 information

Endocrine Glands and the General Principles of Hormone Action

Endocrine Glands and the General Principles of Hormone Action Endocrine Glands and the General Principles of Hormone Action Cai Li, Ph.D. Assistant professor Touchstone Center for Diabetes Research Departments of Physiology and Internal Medicine The University of

More information

Lecture 4 Sunday 30/9/2012

Lecture 4 Sunday 30/9/2012 Inactivation and Detoxification of Xenobiotics and Metabolites in the Liver The liver is one of the most important organs in the body when it comes to detoxifying or getting rid of foreign substances or

More information

BIO 137: CHAPTER 1 OBJECTIVES

BIO 137: CHAPTER 1 OBJECTIVES BIO 137: CHAPTER 1 OBJECTIVES 1. Define the terms anatomy and physiology, and explain their relationship using an example of a human structure with its corresponding function. A. ANATOMY = the study of

More information

Chapter 22 Detoxification and Biotransformational Imbalances

Chapter 22 Detoxification and Biotransformational Imbalances Chapter 22 Detoxification and Biotransformational Imbalances DeAnn Liska, PhD, Michael Lyon, MD, David S. Jones, MD The Detoxification Systems Introduction The concept that toxins accumulate in the body

More information

DRUG METABOLISM CHAPTER. Frank J. Gonzalez and Robert H. Tukey

DRUG METABOLISM CHAPTER. Frank J. Gonzalez and Robert H. Tukey CHAPTER 3 DRUG METABOLISM Frank J. Gonzalez and Robert H. Tukey How Humans Cope with Exposure to Xenobiotics. The ability of humans to metabolize and clear drugs is a natural process that involves the

More information

Guidance for Industry Safety Testing of Drug Metabolites

Guidance for Industry Safety Testing of Drug Metabolites Guidance for Industry Safety Testing of Drug Metabolites U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) February 2008 Pharmacology

More information

INTRODUCTION TO HORMONES

INTRODUCTION TO HORMONES INTRODUCTION TO HORMONES UNIVERSITY OF PNG SCHOOL OF MEDICINE AND HEALTH SCIENCES DISCIPLINE OF BIOCHEMISTRY & MOLECULAR BIOLOGY PBL MBBS II SEMINAR VJ Temple What are hormones? Cells in multi-cellular

More information

Liver Function Tests. Dr Stephen Butler Paediatric Advance Trainee TDHB

Liver Function Tests. Dr Stephen Butler Paediatric Advance Trainee TDHB Liver Function Tests Dr Stephen Butler Paediatric Advance Trainee TDHB Introduction Case presentation What is the liver? Overview of tests used to measure liver function RJ 10 month old European girl

More information

Chapter 18. An Introduction to the Endocrine System. Hormone Chemistry

Chapter 18. An Introduction to the Endocrine System. Hormone Chemistry Chapter 18 An Introduction to the Endocrine System Hormone Chemistry Endocrine System Components endocrine system - glands, tissues, and cells that secrete hormones Copyright The McGraw-Hill Companies,

More information

CHAPTER 3 THE CHEMISTRY OF ORGANIC MOLECULES

CHAPTER 3 THE CHEMISTRY OF ORGANIC MOLECULES CHAPTER 3 THE CHEMISTRY OF ORGANIC MOLECULES 3.1 Organic Molecules The chemistry of carbon accounts for the diversity of organic molecules found in living things. Carbon has six electrons, four of which

More information

Metabolism. Functions of food. Metabolism is all the chemical reactions of the body. source of energy essential nutrients

Metabolism. Functions of food. Metabolism is all the chemical reactions of the body. source of energy essential nutrients Metabolism Functions of food source of energy essential nutrients Metabolism is all the chemical reactions of the body some reactions produce the energy stored in ATP that other reactions consume all molecules

More information

DetoxiGenomic Profile Patient's Copy

DetoxiGenomic Profile Patient's Copy TM DetoxiGenomic Profile Patient: JANE DOE DOB: April 09, 1969 Sex: F MRN: Order Number: Completed: February 26, 2014 Received: February 19, 2014 Collected: February 18, 2014 Security Code: PHASE I Detoxification:

More information

LIVER FUNCTION TESTS

LIVER FUNCTION TESTS LIVER FUNCTION TESTS University of PNG School of Medicine and Health Sciences, Division of Basic Medical Sciences, Discipline of Biochemistry & Molecular Biology VJ Temple 1 What are some of the functions

More information

Nursing 113. Pharmacology Principles

Nursing 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 information

Hormones & Chemical Signaling

Hormones & Chemical Signaling Hormones & Chemical Signaling Part 2 modulation of signal pathways and hormone classification & function How are these pathways controlled? Receptors are proteins! Subject to Specificity of binding Competition

More information

Hormones: Classification. Hormones: Classification. Peptide Hormone Synthesis, Packaging, and Release

Hormones: Classification. Hormones: Classification. Peptide Hormone Synthesis, Packaging, and Release Hormones: Classification Hormones: Classification Be able to give types and example. Compare synthesis, half-life and location of receptor 1. Peptide or protein hormones Insulin from amino acids 2. Steroid

More information

Preliminary MFM Quiz

Preliminary MFM Quiz Preliminary MFM Quiz 1. The major carrier of chemical energy in all cells is: A) adenosine monophosphate B) adenosine diphosphate C) adenosine trisphosphate D) guanosine trisphosphate E) carbamoyl phosphate

More information

Biological molecules:

Biological molecules: Biological molecules: All are organic (based on carbon). Monomers vs. polymers: Monomers refer to the subunits that, when polymerized, make up a larger polymer. Monomers may function on their own in some

More information

Detoxification Pathways. Theory and Application to Practice

Detoxification Pathways. Theory and Application to Practice Detoxification Pathways Theory and Application to Practice 1 Detoxification Pathways Failure to detoxify Accumulation of Toxins Detoxification mechanism Importance to practitioner Phase 1 Biotransformation

More information

Drug Excretion. Renal Drug Clearance. Drug Clearance and Half-Life. Glomerular Filtration II. Glomerular Filtration I. Drug Excretion and Clearance

Drug Excretion. Renal Drug Clearance. Drug Clearance and Half-Life. Glomerular Filtration II. Glomerular Filtration I. Drug Excretion and Clearance t/.drugexcretion AINTRAVENOUSDOSE 36848765430TIME(hours) t/ Drug Excretion Dr. Robert G. Lamb Professor Pharmacology & Toxicology Drug Excretion and Clearance Drug Excretion: is the movement of drug from

More information

Detoxification & Your Health

Detoxification & Your Health Detoxification & Your Health Detoxification is the metabolic process your body uses to transform and eliminate toxins. The process can occur in two steps, called Phase I and Phase II. Phase I is our first

More information

8/20/2012 H C OH H R. Proteins

8/20/2012 H C OH H R. Proteins Proteins Rubisco monomer = amino acids 20 different amino acids polymer = polypeptide protein can be one or more polypeptide chains folded & bonded together large & complex 3-D shape hemoglobin Amino acids

More information

NO CALCULATORS OR CELL PHONES ALLOWED

NO CALCULATORS OR CELL PHONES ALLOWED Biol 205 Exam 1 TEST FORM A Spring 2008 NAME Fill out both sides of the Scantron Sheet. On Side 2 be sure to indicate that you have TEST FORM A The answers to Part I should be placed on the SCANTRON SHEET.

More information

Sickle cell anemia: Altered beta chain Single AA change (#6 Glu to Val) Consequence: Protein polymerizes Change in RBC shape ---> phenotypes

Sickle cell anemia: Altered beta chain Single AA change (#6 Glu to Val) Consequence: Protein polymerizes Change in RBC shape ---> phenotypes Protein Structure Polypeptide: Protein: Therefore: Example: Single chain of amino acids 1 or more polypeptide chains All polypeptides are proteins Some proteins contain >1 polypeptide Hemoglobin (O 2 binding

More information

Drug Metabolism. Importance of Drug Metabolism. Importance of Drug Metabolism. Prof. Patrick Davis Basic Medicinal Chemical Principles

Drug Metabolism. Importance of Drug Metabolism. Importance of Drug Metabolism. Prof. Patrick Davis Basic Medicinal Chemical Principles Drug Metabolism Prof. Patrick Davis Basic Medicinal Chemical Principles PR 143M Fall-08 The basic premise: Lipophilic Drugs --> ydrophilic Metabolites (ot Excreted) (Excreted) Water soluble => increased

More information

Carbohydrates, proteins and lipids

Carbohydrates, proteins and lipids Carbohydrates, proteins and lipids Chapter 3 MACROMOLECULES Macromolecules: polymers with molecular weights >1,000 Functional groups THE FOUR MACROMOLECULES IN LIFE Molecules in living organisms: proteins,

More information

QSAR. The following lecture has drawn many examples from the online lectures by H. Kubinyi

QSAR. The following lecture has drawn many examples from the online lectures by H. Kubinyi QSAR The following lecture has drawn many examples from the online lectures by H. Kubinyi LMU Institut für Informatik, LFE Bioinformatik, Cheminformatics, Structure independent methods J. Apostolakis 1

More information

THE HUMAN BODY SYSTEMS

THE HUMAN BODY SYSTEMS Name Period Date THE HUMAN BODY SYSTEMS System Function Diagram Major Organs Digestive 1. take in food (ingestion) 2. digest food into smaller molecules and absorb nutrients 3. remove undigestable food

More information

Ionization of amino acids

Ionization of amino acids Amino Acids 20 common amino acids there are others found naturally but much less frequently Common structure for amino acid COOH, -NH 2, H and R functional groups all attached to the a carbon Ionization

More information

Chapter 3 Molecules of Cells

Chapter 3 Molecules of Cells Bio 100 Molecules of cells 1 Chapter 3 Molecules of Cells Compounds containing carbon are called organic compounds Molecules such as methane that are only composed of carbon and hydrogen are called hydrocarbons

More information

Lecture 6: Cholesterol (Ch. 9.1e, 9.2b, 19.7b,c) & Lipoproteins (Ch. 10.3*, 19.1, 19.7b,c)

Lecture 6: Cholesterol (Ch. 9.1e, 9.2b, 19.7b,c) & Lipoproteins (Ch. 10.3*, 19.1, 19.7b,c) Lecture 6: Cholesterol (Ch. 9.1e, 9.2b, 19.7b,c) & Lipoproteins (Ch. 10.3*, 19.1, 19.7b,c) Next lecture: Fatty Acid Oxidation (Ch. 19.2), Ketone Bodies (Ch. 19.3) and Fatty Acid Biosynthesis (Ch. 19.4)

More information

ORGAN SYSTEMS OF THE BODY

ORGAN SYSTEMS OF THE BODY ORGAN SYSTEMS OF THE BODY DEFINITIONS AND CONCEPTS A. Organ a structure made up of two or more kinds of tissues organized in such a way that they can together perform a more complex function that can any

More information

Overview of Lipid Metabolism

Overview of Lipid Metabolism Overview of Lipid Metabolism Learning Objectives By the end of this lecture the students should be able to understand: Classification of Lipids The digestion, absorption and utilization of dietary lipids

More information

A disaccharide is formed when a dehydration reaction joins two monosaccharides. This covalent bond is called a glycosidic linkage.

A disaccharide is formed when a dehydration reaction joins two monosaccharides. This covalent bond is called a glycosidic linkage. CH 5 Structure & Function of Large Molecules: Macromolecules Molecules of Life All living things are made up of four classes of large biological molecules: carbohydrates, lipids, proteins, and nucleic

More information

Chapter 3: Biological Molecules. 1. Carbohydrates 2. Lipids 3. Proteins 4. Nucleic Acids

Chapter 3: Biological Molecules. 1. Carbohydrates 2. Lipids 3. Proteins 4. Nucleic Acids Chapter 3: Biological Molecules 1. Carbohydrates 2. Lipids 3. Proteins 4. Nucleic Acids Elements in Biological Molecules Biological macromolecules are made almost entirely of just 6 elements: Carbon (C)

More information

Biological importance of metabolites. Safety and efficacy aspects

Biological 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 information

Proteins and Nucleic Acids

Proteins and Nucleic Acids Proteins and Nucleic Acids Chapter 5 Macromolecules: Proteins Proteins Most structurally & functionally diverse group of biomolecules. : o Involved in almost everything o Enzymes o Structure (keratin,

More information

Eating, pooping, and peeing THE DIGESTIVE SYSTEM

Eating, pooping, and peeing THE DIGESTIVE SYSTEM THE DIGESTIVE SYSTEM Ingested food is not technically in the body until it is absorbed so it needs to be: Mechanically and chemically reduced Transported by the blood to the cells Large portions are not

More information

Phase II Drug Metabolism

Phase II Drug Metabolism 2 Phase II Drug Metabolism Petra Jančová 1 and Michal Šiller 2 1 Department of Environmental Protection Engineering, Faculty of Technology, Tomas Bata University, Zlin, 2 Department of Pharmacology and

More information

Endocrine System: Practice Questions #1

Endocrine System: Practice Questions #1 Endocrine System: Practice Questions #1 1. Removing part of gland D would most likely result in A. a decrease in the secretions of other glands B. a decrease in the blood calcium level C. an increase in

More information

Chapter I Overview Chapter Contents

Chapter I Overview Chapter Contents Chapter I Overview Chapter Contents Table Number Contents I-1 Estimated New Cancer Cases and Deaths for 2005 I-2 53-Year Trends in US Cancer Death Rates I-3 Summary of Changes in Cancer Incidence and Mortality

More information

The Endocrine System

The Endocrine System Essentials of Human Anatomy & Physiology Elaine N. Marieb Seventh Edition Chapter 9 The Endocrine System Slides 9.1 9.48 Lecture Slides in PowerPoint by Jerry L. Cook The Endocrine System Second messenger

More information

FACT SHEET TESTETROL, A NOVEL ORALLY BIOACTIVE ANDROGEN

FACT SHEET TESTETROL, A NOVEL ORALLY BIOACTIVE ANDROGEN FACT SHEET TESTETROL, A NOVEL ORALLY BIOACTIVE ANDROGEN General Pantarhei Bioscience B.V. is an emerging specialty pharmaceutical company with a creative approach towards drug development. The Company

More information

Absorption of Drugs. Transport of a drug from the GI tract

Absorption of Drugs. Transport of a drug from the GI tract Absorption of Drugs Absorption is the transfer of a drug from its site of administration to the bloodstream. The rate and efficiency of absorption depend on the route of administration. For IV delivery,

More information

An overview of the relations between polymorphisms in drug metabolising enzymes and drug transporters and survival after cancer drug treatment

An overview of the relations between polymorphisms in drug metabolising enzymes and drug transporters and survival after cancer drug treatment Cancer Treatment Reviews (2009) 35, 18 31 available at www.sciencedirect.com journal homepage: www.elsevierhealth.com/journals/ctrv ANTI-TUMOUR TREATMENT An overview of the relations between polymorphisms

More information

1.4: Carbohydrates and Lipids pg. 29 38

1.4: Carbohydrates and Lipids pg. 29 38 UNIT 1: Biochemistry 1.4: Carbohydrates and Lipids pg. 29 38 Carbohydrates Function, primary energy source for the cell, can also be a structural component of cells and organisms. Carbohydrates are the

More information

The chemical reactions inside cells are controlled by enzymes. Cells may be specialised to carry out a particular function.

The chemical reactions inside cells are controlled by enzymes. Cells may be specialised to carry out a particular function. 12.1 What are animals and plants built from? All living things are made up of cells. The structures of different types of cells are related to their functions. to relate the structure of different types

More information

Worksheet 13.1. Chapter 13: Human biochemistry glossary

Worksheet 13.1. Chapter 13: Human biochemistry glossary Worksheet 13.1 Chapter 13: Human biochemistry glossary α-helix Refers to a secondary structure of a protein where the chain is twisted to form a regular helix, held by hydrogen bonds between peptide bonds

More information

REVIEW for BIOLOGY UNIT TEST

REVIEW for BIOLOGY UNIT TEST REVIEW for BIOLOGY UNIT TEST NOTE: The Unit Test will cover everything we have learned in the Biology Unit, starting from cell structures, cell division, various organ systems, disorders, organ donation,

More information

Detoxification & Your Health

Detoxification & Your Health Detoxification & Your Health Detoxification is the metabolic process your body uses to transform and eliminate toxins. The process can occur in two steps, called Phase I and Phase II. Phase I is our first

More information

H H N - C - C 2 R. Three possible forms (not counting R group) depending on ph

H H N - C - C 2 R. Three possible forms (not counting R group) depending on ph Amino acids - 0 common amino acids there are others found naturally but much less frequently - Common structure for amino acid - C, -N, and functional groups all attached to the alpha carbon N - C - C

More information

7 Answers to end-of-chapter questions

7 Answers to end-of-chapter questions 7 Answers to end-of-chapter questions Multiple choice questions 1 B 2 B 3 A 4 B 5 A 6 D 7 C 8 C 9 B 10 B Structured questions 11 a i Maintenance of a constant internal environment within set limits i Concentration

More information

Chapter 5. The Structure and Function of Macromolecule s

Chapter 5. The Structure and Function of Macromolecule s Chapter 5 The Structure and Function of Macromolecule s Most Macromolecules are polymers: Polymer: (poly: many; mer: part) Large molecules consisting of many identical or similar subunits connected together.

More information

Fundamentals of Anatomy & Physiology Course Outline, Objectives and Accreditation Information

Fundamentals of Anatomy & Physiology Course Outline, Objectives and Accreditation Information 201 Webster Building 3411 Silverside Road Wilmington, DE 19810 Phone: 1-888-658-6641 Fax: 1-302-477-9744 learn@corexcel.com www.corexcel.com Course Outline, Objectives and Accreditation Information Chapter

More information

Lecture Overview. Hydrogen Bonds. Special Properties of Water Molecules. Universal Solvent. ph Scale Illustrated. special properties of water

Lecture Overview. Hydrogen Bonds. Special Properties of Water Molecules. Universal Solvent. ph Scale Illustrated. special properties of water Lecture Overview special properties of water > water as a solvent > ph molecules of the cell > properties of carbon > carbohydrates > lipids > proteins > nucleic acids Hydrogen Bonds polarity of water

More information

Curriculum Overview:

Curriculum Overview: Curriculum Overview: The following courses must be completed by all Certified Nutrition Specialist candidates. Courses cannot fulfill multiple curriculum requirements, however, excess nutrition science

More information

Elements in Biological Molecules

Elements in Biological Molecules Chapter 3: Biological Molecules 1. Carbohydrates 2. Lipids 3. Proteins 4. Nucleic Acids Elements in Biological Molecules Biological macromolecules are made almost entirely of just 6 elements: Carbon (C)

More information

4. Which carbohydrate would you find as part of a molecule of RNA? a. Galactose b. Deoxyribose c. Ribose d. Glucose

4. Which carbohydrate would you find as part of a molecule of RNA? a. Galactose b. Deoxyribose c. Ribose d. Glucose 1. How is a polymer formed from multiple monomers? a. From the growth of the chain of carbon atoms b. By the removal of an OH group and a hydrogen atom c. By the addition of an OH group and a hydrogen

More information

How to create and interpret the predictive analysis of a compound

How to create and interpret the predictive analysis of a compound How to create and interpret the predictive analysis of a compound Platform with suite of tools Predict & understand biological effects of small molecules & compounds Predict targets and metabolites, potential

More information

Endocrine Responses to Resistance Exercise

Endocrine Responses to Resistance Exercise chapter 3 Endocrine Responses to Resistance Exercise Chapter Objectives Understand basic concepts of endocrinology. Explain the physiological roles of anabolic hormones. Describe hormonal responses to

More information

Pharmacotherapy in the Elderly. Judy MY Wong

Pharmacotherapy in the Elderly. Judy MY Wong Pharmacotherapy in the Elderly Judy MY Wong judywong@berkeley.edu Percentage of population with prescription and number of medication per individual increase with age Definitions Pharmacology: pharmakon

More information

Biochemistry of Cells

Biochemistry of Cells Biochemistry of Cells 1 Carbon-based Molecules Although a cell is mostly water, the rest of the cell consists mostly of carbon-based molecules Organic chemistry is the study of carbon compounds Carbon

More information

Lipids. There are 2 types of lipids; those that contain the structural component of a fatty acid; and

Lipids. There are 2 types of lipids; those that contain the structural component of a fatty acid; and Lipids Lipids are biomolecules that contain fatty acids or a steroid nucleus. soluble in organic solvents, but not in water. named for the Greek word lipos, which means fat. extracted from cells using

More information

Organic Functional Groups Chapter 7. Alcohols, Ethers and More

Organic Functional Groups Chapter 7. Alcohols, Ethers and More Organic Functional Groups Chapter 7 Alcohols, Ethers and More 1 What do you do when you are in Pain? What do you do when you are in a lot of pain? 2 Functional Groups A functional group is an atom, groups

More information

Energy Production In A Cell (Chapter 25 Metabolism)

Energy 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 information

CHAPTER 9 BODY ORGANIZATION

CHAPTER 9 BODY ORGANIZATION CHAPTER 9 BODY ORGANIZATION Objectives Identify the meaning of 10 or more terms relating to the organization of the body Describe the properties of life Describe the function for the structures of the

More information

AP BIOLOGY 2008 SCORING GUIDELINES

AP BIOLOGY 2008 SCORING GUIDELINES AP BIOLOGY 2008 SCORING GUIDELINES Question 1 1. The physical structure of a protein often reflects and affects its function. (a) Describe THREE types of chemical bonds/interactions found in proteins.

More information

Lecture 6: Single nucleotide polymorphisms (SNPs) and Restriction Fragment Length Polymorphisms (RFLPs)

Lecture 6: Single nucleotide polymorphisms (SNPs) and Restriction Fragment Length Polymorphisms (RFLPs) Lecture 6: Single nucleotide polymorphisms (SNPs) and Restriction Fragment Length Polymorphisms (RFLPs) Single nucleotide polymorphisms or SNPs (pronounced "snips") are DNA sequence variations that occur

More information

William Shaw, Ph.D. The Great Plains Laboratory, Inc., Lenexa, Kansas, USA

William 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 information

INSULIN RESISTANCE, POLYCYSTIC OVARIAN SYNDROME

INSULIN RESISTANCE, POLYCYSTIC OVARIAN SYNDROME 1 University of Papua New Guinea School of Medicine and Health Sciences Division of Basic Medical Sciences Discipline of Biochemistry and Molecular Biology PBL SEMINAR INSULIN RESISTANCE, POLYCYSTIC OVARIAN

More information

The Molecules of Cells

The Molecules of Cells The Molecules of Cells I. Introduction A. Most of the world s population cannot digest milk-based foods. 1. These people are lactose intolerant because they lack the enzyme lactase. 2. This illustrates

More information

Reproductive System & Development: Practice Questions #1

Reproductive System & Development: Practice Questions #1 Reproductive System & Development: Practice Questions #1 1. Which two glands in the diagram produce gametes? A. glands A and B B. glands B and E C. glands C and F D. glands E and F 2. Base your answer

More information

Name: Hour: Elements & Macromolecules in Organisms

Name: 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 information

Chemical Basis of Life Module A Anchor 2

Chemical Basis of Life Module A Anchor 2 Chemical Basis of Life Module A Anchor 2 Key Concepts: - Water is a polar molecule. Therefore, it is able to form multiple hydrogen bonds, which account for many of its special properties. - Water s polarity

More information

Chapter-21b: Hormones and Receptors

Chapter-21b: Hormones and Receptors 1 hapter-21b: Hormones and Receptors Hormone classes Hormones are classified according to the distance over which they act. 1. Autocrine hormones --- act on the same cell that released them. Interleukin-2

More information

Testosterone Therapy for Women

Testosterone Therapy for Women Testosterone Therapy for Women The Facts You Need Contents 2 INTRODUCTION: The Facts You Need... 3-4 CHAPTER 1: Testosterone and Women... 5-9 CHAPTER 2: Testosterone Therapy for Women... 10-14 CONCLUSION:

More information

Cyclooxygenase and NSAIDs

Cyclooxygenase and NSAIDs Cyclooxygenase and NSAIDs Cyclooxygenase An enzyme responsible for the production of prostaglandins Two forms, COX1 and COX2 Contains two separate active sites for prostaglandin synthase One side contains

More information

Name Class Date Laboratory Investigation 24A Chapter 24A: Human Skin

Name Class Date Laboratory Investigation 24A Chapter 24A: Human Skin Name Class Date Laboratory Investigation 24A Chapter 24A: Human Skin Human Anatomy & Physiology: Integumentary System You may refer to pages 386-394 in your textbook for a general discussion of the integumentary

More information

Special report. Chronic Lymphocytic Leukemia (CLL) Genomic Biology 3020 April 20, 2006

Special report. Chronic Lymphocytic Leukemia (CLL) Genomic Biology 3020 April 20, 2006 Special report Chronic Lymphocytic Leukemia (CLL) Genomic Biology 3020 April 20, 2006 Gene And Protein The gene that causes the mutation is CCND1 and the protein NP_444284 The mutation deals with the cell

More information

Integration of Metabolism

Integration of Metabolism I. Central Themes of Metabolism 1. ATP is the universal energy carrier. Integration of Metabolism Bryant Miles 2. ATP is generated by the oxidation of metabolic fuels Glucose Fatty Acids Amino Acids 3.

More information

Chapter 25: Metabolism and Nutrition

Chapter 25: Metabolism and Nutrition Chapter 25: Metabolism and Nutrition Chapter Objectives INTRODUCTION 1. Generalize the way in which nutrients are processed through the three major metabolic fates in order to perform various energetic

More information

Chapter 8. Summary and Perspectives

Chapter 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 information

Antioxidant Products. A comprehensive range of. Antioxidants

Antioxidant Products. A comprehensive range of. Antioxidants Antioxidant Products A comprehensive range of ALB BIL FERR GR Ransel Ransod antioxidant TAS testing TIBC kits TF BIL FERR GR Ransel Ransod TAS TIBC TF UA A FERR GR Ransel Ransod TAS TIBC TF UA ALB GR Ransel

More information

STEM CELL FELLOWSHIP

STEM CELL FELLOWSHIP Module I: The Basic Principles of Stem Cells 1. Basics of Stem Cells a. Understanding the development of embryonic stem cells i. Embryonic stem cells ii. Embryonic germ cells iii. Differentiated stem cell

More information

The harmful use of alcohol in Aboriginal and Torres Strait Islander communities Submission 6

The harmful use of alcohol in Aboriginal and Torres Strait Islander communities Submission 6 SUBMISSION TO INQUIRY INTO THE HARMFUL USE OF ALCOHOL IN ABORIGINAL AND TORRES STRAIT ISLANDER COMMUNITIES Summary Alcohol misuse results in well-known clinical conditions. Alcohol has recently been classified

More information

ANATOMY AND PHYSIOLOGY

ANATOMY AND PHYSIOLOGY ANATOMY AND PHYSIOLOGY Placement: First Year Theory - Anatomy: 60 Physiology: 60 Course Description -The course is designed to assist students to acquire the knowledge of the normal Structure of human

More information

glucose and fatty acids to raise your blood sugar levels.

glucose and fatty acids to raise your blood sugar levels. Endocrine & Cell Communication Part IV: Maintaining Balance (Homeostasis) TEACHER NOTES needs coding 1 Endocrine & Cell Communication Part IV: Maintaining Balance (Homeostasis) 2 AP Biology Curriculum

More information

(Woods) Chem-131 Lec-15 09-4 Carboxyllic acid 1. Carboxylic Acid Derivatives Esters, Acid Anhydrides, Amides, and Acid Halides

(Woods) Chem-131 Lec-15 09-4 Carboxyllic acid 1. Carboxylic Acid Derivatives Esters, Acid Anhydrides, Amides, and Acid Halides (Woods) Chem-131 Lec-15 09-4 Carboxyllic acid 1 Carboxylic Acid Derivatives Esters, Acid Anhydrides, Amides, and Acid Halides The oxidation state of carbon in a carboxylic acid is the highest of the organic

More information

LIVER FUNCTION TESTS

LIVER FUNCTION TESTS MODULE Liver Function Tests 17 LIVER FUNCTION TESTS 17.1 INTRODUCTION Liver function tests are a group of tests done to assess the functional capacity of the liver as well as any cellular damage to the

More information

1. What has a higher stored energy potential per gram, glycogen or triglycerides? Explain.

1. What has a higher stored energy potential per gram, glycogen or triglycerides? Explain. Lipid Metabolism 1. What has a higher stored energy potential per gram, glycogen or triglycerides? Explain. 2. How can excess acetyl CoA trapped in the mitochondria, be utilized as a substrate for fatty

More information

the nature and importance of biomacromolecules in the chemistry of the cell: synthesis of biomacromolecules through the condensation reaction lipids

the nature and importance of biomacromolecules in the chemistry of the cell: synthesis of biomacromolecules through the condensation reaction lipids the nature and importance of biomacromolecules in the chemistry of the cell: synthesis of biomacromolecules through the condensation reaction lipids and their sub-units; the role of lipids in the plasma

More information

BIOLOGICAL MOLECULES OF LIFE

BIOLOGICAL MOLECULES OF LIFE BIOLOGICAL MOLECULES OF LIFE C A R B O H Y D R A T E S, L I P I D S, P R O T E I N S, A N D N U C L E I C A C I D S The Academic Support Center @ Daytona State College (Science 115, Page 1 of 29) Carbon

More information

FGF-1 as Cosmetic Supplement

FGF-1 as Cosmetic Supplement FGF-1 as Cosmetic Supplement Ing-Ming Chiu, Ph.D. Professor, Internal Medicine and Molecular and Cellular Biochemistry The Ohio State University Columbus, Ohio, U.S.A. GENTEON USA Fibroblast Growth Factor

More information

Anatomy & Physiology Bio 2401 Lecture. Instructor: Daryl Beatty Day 1 Intro to Lecture 1

Anatomy & Physiology Bio 2401 Lecture. Instructor: Daryl Beatty Day 1 Intro to Lecture 1 Anatomy & Physiology Bio 2401 Lecture Instructor: Daryl Beatty Day 1 Intro to Lecture 1 Introduction: Daryl Beatty M.S. Microbiology 28 Years Dow, Research & TS&D. Family BC since 2007 More importantly:

More information

Disaccharides consist of two monosaccharide monomers covalently linked by a glycosidic bond. They function in sugar transport.

Disaccharides consist of two monosaccharide monomers covalently linked by a glycosidic bond. They function in sugar transport. 1. The fundamental life processes of plants and animals depend on a variety of chemical reactions that occur in specialized areas of the organism s cells. As a basis for understanding this concept: 1.

More information

Chapter 5: The Structure and Function of Large Biological Molecules

Chapter 5: The Structure and Function of Large Biological Molecules Name Period Concept 5.1 Macromolecules are polymers, built from monomers 1. The large molecules of all living things fall into just four main classes. Name them. 2. Circle the three classes that are called

More information

Gene mutation and molecular medicine Chapter 15

Gene mutation and molecular medicine Chapter 15 Gene mutation and molecular medicine Chapter 15 Lecture Objectives What Are Mutations? How Are DNA Molecules and Mutations Analyzed? How Do Defective Proteins Lead to Diseases? What DNA Changes Lead to

More information

Structure of proteins

Structure of proteins Structure of proteins Primary structure: is amino acids sequence or the covalent structure (50-2500) amino acids M.Wt. of amino acid=110 Dalton (56 110=5610 Dalton). Single chain or more than one polypeptide

More information

MOLECULAR CELL BIOLOGY: ESSAY OUTLINE. What are peroxisomes? What do they do? And, how are proteins targeted to them?

MOLECULAR CELL BIOLOGY: ESSAY OUTLINE. What are peroxisomes? What do they do? And, how are proteins targeted to them? MOLECULAR CELL BIOLOGY: ESSAY OUTLINE What are peroxisomes? What do they do? And, how are proteins targeted to them? Are they related to the ER/Golgi? Are they more like mitochondria? Or, are they completely

More information