PHRM 3050

The Biochemical Basis of Disease and Drug Action

Michael G. Bartlett, Ph.D.

PHRM 3050 Fall 2014

The Biochemical Basis of Disease and Drug Action

Instructor: Michael G. Bartlett, Ph.D. Office: RC Wilson Room 420

Class: M 11:15-12:05, W 10:10-12:05 Phone: 542-5390

Room: 120 College of Pharmacy E-mail: mgbart@uga.edu

The purpose of this course is to train you in biochemistry. Biochemistry is the basis of

physiological function, which determines the pharmacology of drugs. It is the basis of

chemotherapy for infectious diseases where the biochemical differences of the infectious

agents (bacteria, fungi, protozoa and virus) are exploited in order to bring about the death

of the organism without affecting the host. It is the basis of the chemotherapy for cancer

where the biochemical differences between the cancer cell and the normal cell are

exploited to bring about cell death. Finally, it is the basis of some pharmacotherapies

where the target of the drug is an enzyme, which is inhibited. The importance of

knowledge of biochemistry in the understanding of diseases, of how drugs work, the role

of vitamins and minerals in metabolism and the rational selection of pharmacotherapies

cannot be over emphasized.

Method of Evaluation

There will be 3 hourly exams during the semester plus a comprehensive final exam

during finals week, each will count 24% of your final grade. These may consist of a

combination of multiple choice, multiple-multiple choice (keyed questions), short answer,

numerical problems and essay questions. You are expected to know the names of

enzymes, the structure and name of the substrates, the products of enzymatic reactions

and the name and structure of any known inhibitors of the process.

Exam Dates

Exam I 8 am, Monday September 15th

, 2014

Exam II 8 am, Friday September 26th

, 2014

Exam III 8 am, Friday October 17th

, 2014

Final Exam 8 am, Monday November 11th

, 2014

The remaining four percent of your grade will be determined by your completion of

minute papers assigned throughout the semester. Minute papers are used to quickly

determine the impact of any lecture and to allow the instructor make adjustments to the

course prior to examinations. For these papers, you are asked to answer three questions:

1) What is the most significant fact that you learned today; 2) What is the most unclear

point from todays lecture; and 3) What is the most interesting point from todays lecture.

The minute paper is a pass/fail type of assignment with no correct or incorrect answers.

The class is divided into four laboratory sections for skills labs. One section will be

responsible for turning in a paper each day. Therefore, each student should only have to

turn in a minute paper once every two weeks.

Grading Scale for PHRM 3050

Grade %

A 92.00-100

A- 89.50-91.99

B+ 87.00-89.49

B 82.00-86.99

B- 79.50-81.99

C+ 77.00-79.49

C 72.00-76.99

C- 69.50-72.00

D 59.50-69.49

F 0.00-59.49

Regrading Policy

Students who believe that an error has occurred in the grading of an assignment should

alert the instructor within two weeks of the date of the assignment. Additional points

may be awarded at the discretion of the instructor. No grades will be changed once the

two-week period for regrading has passed.

Make-Up Examination Policy

Students may be permitted to take a make-up examination under the following

conditions. 1) The student was medically unable to be in school and appropriate proof is

provided to the instructor. 2) There is a conflict with another University or College

academic function and the student has informed the instructor at least 48 hours prior to

the examination. 3) Other personal emergencies will be handled on a case-by-case basis.

Make-up tests will not contain any multiple choice questions and will be primarily essay

in nature. The examinations may take longer than the time normally allotted for standard

assignments. Make-up examinations must occur within a week of the original test date or

the student will receive a zero for the assignment.

Calculator Policy

Calculators may be permitted on some exams. During the exams, only basic scientific

calculators with simple functions such as addition, subtraction, multiplication, division,

logarithms and exponents will be allowed. Examples of acceptable calculators are the

Casio 100-300, Sharp 500 and TI-30 series. The instructor must approve other

calculators 24 hours before the exam begins. Calculators with graphing and

differentiating capabilities are NOT allowed. Use of calculators on cell phones or PDAs

is NOT allowed. Use of an unauthorized calculator will result in a zero for the

examination and will be considered a violation of the UGA academic honesty policy and

the College of Pharmacy Professionalism Policy.

Class Attendance and Absences

Students are expected to attend class regularly. A student who incurs an excessive

number of absences may be dismissed from a class at the discretion of the instructor. If

the student must miss an exam due to illness or another emergency, the instructor should

be informed, either directly or through the Deans office, of the situation prior to the

exam being given. The student will then be given a make-up exam as soon as possible

after the student returns to class. An unexcused absence from an exam will result in a

zero for that exam at the discretion of the instructor.

Academic Honesty

The University of Georgia Honor Code, Academic Policy and the College of Pharmacy

Professionalism Policy provide the framework for all assignments and interactions

associated with this course. In addition, all academic work must meet the standards

contained in "A Culture of Honesty." Students are responsible for informing themselves

about those standards before performing any academic work.

Texts

Harpers Illustrated Biochemistry, 29th Edition by Murray, Bender, Botham, Kennelly,

Rodwell and Weil.

Supplemental Reading Sources

Biochemistry by Berg, Tymoczko and Stryer

Medical Biochemistry by Bhagavan

Principles of Biochemistry with a Human Focus by Garrett and Grisham

Biochemistry by Garrett and Grisham

Medicinal Chemistry Edward Foye

Textbook of Biochemistry with Clinical Correlations by Thomas Devlin

Biochemistry by Donald and Judith Voet

The Pharmacological Basis of Therapeutics by Goodman and Gilman

Biochemistry and Disease by Cohn and Roth

Topical Outline of Material to be Covered

I. Characteristics of Proteins (Ch. 3-5)

A. Amino Acids

B. Peptide Bond

C. Protein Structure and Function

II. The Role of Enzymes in Biochemical Processes (Ch. 7-9)

A. Regulation of Enzymes

B. Catalytic Properties of Enzymes

C. Enzyme-Substrate Interactions

D. The Active Site of an Enzyme

E. Enzyme Kinetics (Michaelis-Menten)

F. Enzyme Inhibition Mechanisms

G. Enzyme Regulation

III. The Metabolism of Carbohydrates (Ch. 14)

A. Glycolysis (Ch. 18)

B. Gluconeogenesis (Ch. 20)

C. The Tricarboxylic Acid Cycle (Ch. 17)

D. Electron Transport Chain & Ox. Phos. (Ch. 13)

IV. Storage and Retrieval of Glucose (Ch. 19)

A. Glycogen Formation

B. Glycogen Metabolism

V. The Metabolism of Lipids (Ch. 15, 22, 25)

A. Lipids as an Energy Source and Energy Storage

1. Nomenclature

2. Cell Membranes

B. Mobilization of Fatty Acids

C. Fate of Glycerol

D. -Oxidation

1. Saturated Fatty Acids

2. Unsaturated Fatty Acids

E. Diabetes Mellitus

VI. Metabolism of Amino Acids (Ch. 28-30)

A. Essential versus Non-essential Amino Acids

B. Metabolic Fate of Amino Acids

C. Pyridoxal Phosphate

D. Urea Cycle

E. Utilization of Amino Acids for the Synthesis of Other Biomolecules

1. Neurotransmitters

a. Acetylcholine, Dopamine, Norepinephrine,

Serotonin, GABA

b. Phenylketouria

2. Autocoids and Hormones

a. Histamine, Thyroxin, Epinephrine

3. Creatine, Phosphocreatine, Creatinine

4. Heme, Bilirubin, Jaundice

VII. One Carbon Transfers (Ch. 30)

A. Tetrahydrofolic Acid and One-Carbon Unit Transfers.

B. Folic Acid Pathway

C. S-Adenosylmethionine (SAM) and Methyl Group Transfers.

D. The Active Methyl Cycle.

VIII. Biosynthesis & Metabolism of Nucleotides and Nucleosides (Ch. 32-33)

A. De Novo Synthesis

1. Pyrimidine Nucleotides

2. Purine Nucleotides

B. Salvage Pathway

1. Pyrimidines

2. Purines

3. Metabolic Defects in Purine and Pyrimidine Metabolism

4. Targets for Chemotherapeutic Intervention

IX. Vitamins, Cofactors for Metabolism (Ch. 44 and Handout)

A. Water Soluble Vitamins

1. The B Complex Vitamins

2. Vitamin C

B. Fat Soluble Vitamins

Note: The course syllabus is a general plan for the course; deviations announced to the

class by the instructor may be necessary.

o-

o-

o-

o O

M

to

O=

O o

l O

-O

J-

O-

O-

O X

I

I

I

0

=0

o

tit

tO o

o

0=0 o

x-

o I

I 0=

0 o

0>

2

O-

O-

O-

O-

O +

I I

I I

X M

IO

N>

K>

I 0

=0

o

I

\\ l O

-O

-O

0=

0 O

l O

-O

-O

X

XX

0

=0

o

l 0

-0

X

X

0

I 0=

0

I I

\ l p

z

-0

-0

-0

-0

//

I I

X I

X X

10

+

\\ l + 0

0

0

-0

o

1 0=

0 o

X w

o l -

o X

I 0

=0

o

o

o

0=

0

o

z W

M O

-O

-O

0=

0 o

l co

-0-0

to

0=

0 o

XX

IO

I 0=

0

redu

ctio

n

oxid

atio

n

OH

OH

FAD

FADH

2

00

HO

OH

H2N

redu

cUon

oxid

atio

n

HQ

vv

H2

N

OH

I o

NAD*

NA

DH

ATP

ADP

hexo

kina

se

OH Gl

ucos

c-6-

phos

phal

e

O II O

-P

-

phos

phog

luco

se is

omei

ase

.OH

'OH

ATP

ADP

I Fr

ucto

sc-6

-pho

spha

te

6-ph

osph

ofru

cto-

1 -ki

nasc

O O-

R

OH fn

icto

se-1

,6-b

ipho

spha

le (F

BP)

Prim

ing s

tage

o-p-

o.

.O-P

-O O

R H

O-

OH

fruc

tose

-1.6

-bip

hosp

hale

(F

BP)

hcmi

keta

l fur

anos

e for

m

Clea

vage

Stag

e

Glyc

etal

dehy

de 3-

phos

phai

c (G

AP)

I

GAP

Dehy

drog

cnas

e OH

O O-

P-O 6 Gl

ycer

alde

hyde

3-ph

osph

ale (G

AP)

Ott

-O

P-0

Phos

phog

lyce

rale

ki

nase

\

NAD+

NA

DH

o 1,

3-Bi

phos

phog

lyce

ratc

(1

.3-B

GA)

ADP

ATP

-0

-IO

H O

3-ph

osph

ogly

cera

le (3

-PGA

)

Phos

phog

lycc

ratc

Mu

tase

Ener

gy Pr

oduc

tion

stag

e

X

0-

O

1 OH

O 2-

phos

phog

lyce

rate

(2

-PGA

) eno

lase

H20

~-c-o

. ""in

, L-

Laci

ale

Laci

ale d

ehyd

roge

nase

h CH, Py

niva

te

*C-O- I

NAD+

NA

DH

Pymv

ate

Kina

se

ATP

ADP

Phosph

ocnolp

yruvat

e (P

EP)

-10-

Galactose Metabolism CHjOH

OH -O H ATP ADP CHjOH

H OH

Galactose

Galactokinase oh h

0POjJ

H OH Galactose-1 -phosphate

CHjOH

OH

CH2OH

UDP-Glucose

OH H

| H OH

UDP-Galaetose

OPOjJ Galactose-1-phosephate CH0H Uridyl Transferase H oh

Galactose-1 -phosphate

OPOj3

CHjOH

OH

Glucose-1 -phosphate

CHjOH

OH H

0. H

UOP UDP-Galactose 4-Epimerase OH

H OH

UDP-Galactose

UDP

H oh

UDP-Glucose

CHjOPOj'

Phosphoglucomutase OPO,J

OH H

OH

H OH

Glucose-1 -phosphate

OH

H OH

Glucose-6-phosphate

Fructose Metabolism

CH2OH CH2OH ATP HO

CH2OH CH2OPO3 -2

OH Fructokinase

HO

OH

OH Fructose

OH

Fructose-1 -phosphate

CH2OH CH2OPO3-2

HO.

OH Fructose-1 -phosphate Aldolase

-opo,-2

:O

OH

CHO

OH

CH2OH

OH

Fructose-1 -phosphate Dihydroxyacetone phosphate Glyceraldehyde

CHO ATP ADP

-OH

CHO

CH2OH Triose Kinase -OH

-OPO,"2

Glyceraldehyde Glyceraldehyde-3 -phosphate

COj

NADH

Dihy

drol

ipoy

l Deh

ydro

geiu

se

NAD*

TPP=

thim

ninc

pyro

phos

plul

c Li

ps L

tpoa

miJe

Co

A-SH

= C

ocru

ymc

A

Acet

yl C

oA's

abili

ty to

ente

r the

TCA

cycl

e de

pend

s on

the c

once

ntra

tion

and

availa

bility

of Ox

aloa

ceta

te. Wh

en ca

rboh

yrat

es in

take

is lo

w, as

in fa

sting

or sta

rvatio

n, or

impr

oper

ly ut

ilized

as in

Diab

etes

. Ox

aloa

ceta

te is

unav

aila

ble t

o mak

e th

e cyc

le run

. Ace

tyl C

oA u

nder

goes

anot

her f

ate

COO"

NADH

Mala

te De

hydr

ogen

ase

FADH

2

N3 I

coo-' S

ucdn

yl C

oA S

ynth

etas

e | CH

2 H

IH

GTP

-C-S

CoA

Succ

inyl

CoA

COO"

CH2 H

JH O

:=

C CO

O" a-

Kelo

gluu

rale

a-

Keto

glul

arat

e Deh

ydro

gena

se

CO2 NA

DH

Elec

tron

Tran

spor

t Cha

in

NADH

-CoE

nzym

e Q

CoEn

zyme

Q -

Cyt

C Re

duct

ase

Redu

ctas

e N

AD

H

NADH

Fatt

y Acy

l Co

A De

hydr

ogen

ase (F

AD)

Cyto

chro

me C

Ox

idas

e

CytC

CytC

Gly c

erol

-3 -p

hosp

hate

De

hydr

ogen

ase (F

AD)

Succ

inyl

Deh

ydro

gena

se (F

AD)

H2O

Oxid

ativ

e Pho

spho

ryla

tion

Ma

trix

AT

P Sy

ntha

se

ADP

+ Pi

AT

P

Comp

lex

I Co

mple

x III

Co

mple

x IV

H+

H+

H+

IMS

HH

Cyto

sol

PHRM 3050 Fall 2014 Course PacketPHRM 3050 Syllabus 2014PHRM 3050 Fall 2013 Course PacketPHRM 3050 Syllabus 2013PHRM 3050 Fall 2012 Course PacketPHRM 3050 Syllabus 2012.pdfPHRM 3050 Fall 2012 Course PacketPHRM 3050 Syllabus 2012.pdfPHRM 3050 Fall 2012 Course PacketPHRM 3050 Syllabus 2012.pdfPHRM 3050 Fall 2011 Course PacketPHRM 3050 1.pdfPHRM 3050 2PHRM 3050 3PHRM 3050 4PHRM 3050 5

PHRM 3050 2011 Test 1PHRM 3050 2012 Test 1PHRM 3050 2011 Test 2PHRM 3050 2012 Test 2PHRM 3050 2011 Test 3PHRM 3050 2012 Test 3

PHRM 3050 2013 Test 1PHRM 3050 2013 Test 2PHRM 3050 2013 Test 3