Biochemical Toxicology I
EVHS 401A
 
Fall 1998
Thursdays, 5:15 - 6:30 p.m.
Medical School, WG-315
Lecturers:
G. David McCoy, PhD [368-5963] Rm. WG-19
Hasan Mukhtar, PhD [368-1127] Rm. SOM BRB #521

Referenced Texts:

A Textbook in Modern Toxicology, Hodgson and Levi (2nd ed)
Introduction to Drug Metabolism, Gibson and Skett

Topics to Be Covered:

Week Lecture Lecturer Reference
I
INTRODUCTION TO TOXICOLOGY
a. Course organization
b. Definitions and scope
McCoy
Chap. 1 Hodgson
and 6 Gibson
II
INTRODUCTION TO XENOBIOTIC METABOLISM
a. Cellular and subcellular fractionation
b. Enzyme kinetics
c. Enzyme purification
d. Marker enzymes
McCoy (Handouts)
III
BIOLOGICAL OXIDATION I
a. Definition of oxidative processes
b. Redox reactions
c. Enzyme classes catalyzing biological oxidations
McCoy Chap. 3 Hodgson
IV
BIOLOGICAL OXIDATION II
a. Role of oxygen in biological oxidations
b. Biological reduction of oxygen
c. Enzymes which utilize reduced forms of oxygen
d. Role of biological oxidation in xenobiotic metabolism
McCoy Chap. 1 Gibson
V
PHASE I REACTIONS; CYTOCHROME P-450
a. Endoplasmic reticulum electron transport components
b. Reactions catalyzed by the enzyme system
c. Mechanism and regulation of the enzyme activity
d. P450 as an enzyme family
McCoy Chap. 4 Hodgson and 2 Gibson
VI
PHASE I REACTIONS: OTHER BIOLOGICAL OXIDASES
a. Flavin mono-oxygenase - reactions and tissue distribution
b. Aldehyde oxidase - reactions catalyzed
c. Alcohol dehydrogenase - reactions catalyzed
d. Prostaglandin syntheses - reactions catalyzed and
role in extrahepatic oxidations
McCoy Chap. 3 Hodgson and 1, 2 Gibson
VII EXAM I McCoy  
VIII
MODIFICATION OF METABOLISM - I
a. Nutritional effects
b. Physiological effects
c. Genetic effects
d. Chemical an environmental effects
McCoy Chap. 6 Hodgson and 3 Gibson
IX
PHASE II REACTIONS
a. Role of glutathione in detoxification
b. Glutathione transferases
c. Other enzymes involved in glutathione metabolism
d. Epoxide hydrase
e. Enzymes involved in conjugation reactions
Mukhtar Chap. 3 Hodgson and 2 Gibson
X
FUNDAMENTALS OF BIOLOGICAL MEMBRANE LIPID PEROXIDATION
a. Importance of lipid peroxidation in toxicology
b. Chemistry of lipid peroxidation: Initiation by carbon-centered and by oxygen-centered radicals; role of iron
c. Propagation of lipid peroxidation; importance of iron in autocatalytic spread of lipid peroxidation
d. Termination of lipid peroxidation; biological consequences of termination
e. Role of vitamin E and glutathione in protection against lipid peroxidation
f. Role of superoxide dismutase and glutathione peroxidases in protection against lipid peroxidation
g. Sequestration of iron
d. Definition of oxidative stress
h. Xenobiotics (drugs, poisons, solvents, etc.)
i. Iron overload
j. Lipid peroxidation initiated by partially reduced species of oxygen (superoxide and hydroxyl radicals).
Mukhtar Chap. 3 and 8 Hodgson

Handouts - book chapter

XI
MODIFICATION OF METABOLISM - II
a. Effects of activators, inducers and inhibitors
McCoy Chap. 6 Hodgson, 4 and 5 Gibson
XII EXAMPLES OF TOXIC ACTION I McCoy Chap. 7 Hodgson
XIII EXAMPLES OF TOXIC ACTION II McCoy Chap. 8 Hodgson
XIV EXAM II McCoy  

Back to the Graduate Courses Page

[Toolbar]