MBMB 451b

Eric C. Niederhoffer, Ph.D.

Associate Professor of Biochemistry and Molecular Biology

Southern Illinois University School of Medicine

Rm 211 Neckers, 453-6467, eniederhoffer@siumed.edu

Copyright 2000, E.C. Niederhoffer. All Rights Reserved.
All trademarks and copyrights are the property of their respective owners.

Peter M. D. Hardwicke, Ph.D.

Professor of Biochemistry and Molecular Biology

Southern Illinois University School of Medicine

Rm 210 Neckers, 453-6469, phardwicke@siumed.edu

GENERAL INFORMATION:

MBMB 451b is the second semester of a two-semester biochemistry course for undergraduate and graduate students. We will cover enzymes, carbohydrate metabolism, membranes, lipid metabolism, amino acid metabolism, and nucleotide metabolism. Students should be familiar with analytical, organic, and physical chemistry as well as common mathematical approaches to problem solving. Familiarity with the internet is encouraged and recommended. Class meets on TR from 1-2:15 p.m. in the Life Science III Auditorium.

RESOURCES:

The course will use Biochemistry by Voet and Voet (2nd edition, John Wiley & Sons, Inc., 1995), which is available from the campus bookstore. Appropriate readings are indicated in this handout, but you may wish to include additional materials (the WWW is a good example, check http://www.wiley.com/college/voet586501/bookmarks.html).

Two alternatives or supplements are Fundamentals of Biochemistry by Voet, Voet & Pratt (John Wiley & Sons, Inc., 1999, ISBN 0-471-58650-1), which includes a useful Biochemical Interactions CD-ROM for guided and interactive exercises, and Biochemistry by Garrett & Grisham (2nd edition, Saunders College Publishing, 1999, ISBN 0-03-022318-0).

The KEGG graphical pathway maps may be of use in learning the material concerning the various metabolic pathways.

You may find it beneficial to practice the problems that are included in the textbook! Remember, it is up to you to develop a comprehensive understanding of all the material that is assigned and presented. Lectures will focus on important concepts and illustrate key points. Select materials may be posted to this course web page. To develop a comprehensive understanding (your key goal), we suggest that you read the material several times, attend class, ask appropriate questions, practice problems from various resources (see On-Line quiz and the sample problems that appear in the course outline), and check this MBMB 451b Web site frequently.

GRADING POLICY:

Your performance in this course will be based on 2 tests and the comprehensive final exam. Each of the two tests and the final exam will consist of a combination of short-answer, multiple-choice, and problem-solving questions. Tests are scheduled for Thursday 9 March and Thursday 4 May 2000. We will use the University's designated final exam day and time (Monday 8 May 2000 from 7:50-9:50 am).

As a general policy, there will be no make-up examinations.

COURSE OUTLINE:

This section will be presented by Eric C. Niederhoffer (18 January - 9 March 2000)

An On-line Quiz will allow you to assess your learning as you progress through the course material.

Lectures will be made available on-line within a reasonable length of time after the class meeting. In order to listen to the on-line lecture, you will need to have RealAudio installed on the computer. Follow the link to RealAudio and directions supplied by the company. Remember, you can scan through each lecture with RealAudio to the portion you want to listen to.

Introduction to enzymes (Read pp. 332-344)

• Historical perspective
• Substrate specificity
• Coenzymes
• Regulation of enzymatic activity
• Enzyme nomenclature
• Problems 1, 3, 4, 6, and 7

Rates of enzymatic reactions (Read pp. 345-370) (PDF file for topic)

• Chemical kinetics
• Enzyme kinetics (sample problem)
• Inhibition (sample problem)
• Effects of pH
• Bisubstrate reactions
• Problems 1, 3, 4, 6, 7, 8, 9, and 12

Enzymatic catalysis (Read pp. 371-410) (PDF file for topic)

• Catalytic mechanisms (sample problem)
• Lysozyme
• Serine proteases (sample problem)
• Glutathione reductase (sample problem)
• Problems 2, 3, 4, 9, 10, 11, 14, 19, 21, and 22

Sugars and polysaccharides (Read pp. 251-276) (PDF file for topic)

• Monosaccharides (sample problem, sample problem)
• Polysaccharides (sample problem)
• Glycoproteins (sample problem)
• Problems 1, 2, 5, 8, 9, 10, 12, 13, and 16

Introduction to metabolism (Read pp. 412-442) (PDF file for topic)

• Metabolic pathways (KEGG graphical pathway maps)
• Organic reaction mechanisms
• Experimental approaches to the study of metabolism
• Thermodynamics of phosphate compounds
• Oxidation-reduction reactions
• Thermodynamics of life
• Problems 1, 3, 4, 6, 7, 9, 11, 12, and 13

Glycolysis (Read pp. 443-483) (PDF file for topic)

• Glycolytic pathway
• Reactions of glycolysis (sample problem)
• Fermentation
• Control of metabolic flux (sample problem)
• Metabolism of other hexoses
• Problems 1, 2, 4, 5, 6, 7, 8, and 9

Glycogen metabolism (Read pp. 484-512) (PDF file for topic)

• Glycogen breakdown
• Glycogen synthesis
• Control of glycogen metabolism
• Glycogen storage diseases
• Problems 2, 3, 4, 6, and 7

Citric acid cycle (Read pp. 538-562) (PDF file for topic)

• Cycle overview
• Metabolic sources of acetyl-coenzyme A
• Citric acid cycle enzymes (sample problem)
• Citric acid cycle regulation
• Amphibolic nature of the citric acid cycle
• Problems 1, 2, 3, 7, 8, 9, and 10

Electron transport and oxidative phosphorylation (Read pp. 563-598) (PDF file for topic)

• The mitochondrion
• Electron transport
• Oxidative phosphorylation
• Control of ATP production
• Problems 1, 2, 3, 5, 6, 7, and 9

Other pathways of carbohydrate metabolism (Read pp. 599-625) (PDF file for topic)

• Gluconeogenesis (sample problem)
• Glyoxylate pathway
• Biosynthesis of oligosaccharides and glycoproteins
• Pentose phosphate pathway (sample problem)
• Problems 1, 2, 5, 6, and 7

Photosynthesis (Read pp. 626-661) (PDF file for topic)

• Chloroplasts
• Light reactions
• Dark reactions
• Problems 2, 3, 4, 5, 8, and 9

First Examination - Enzymes, sugars and polysaccharides, carbohydrate metabolism and photosynthesis
(Thursday 9 March 2000)

Exam answer key

Exam #1 3/9/00

answer key (pdf)  click here for my comments

SPRING BREAK

This section will be presented by Peter Hardwicke (21 March - 4 May 2000)

Lipids and membranes (Read pp. 277-329)

• Lipid classification
• Properties of lipid aggregates
• Biological membranes
• Membrane assembly and protein targeting
• Lipid-linked proteins and lipoproteins

Transport through membranes (Read pp. 513-537)

• Thermodynamics of transport
• Kinetics and mechanisms of transport
• ATP-driven active transport
• Ion gradient-driven active transport

Lipid metabolism (Read pp. 662-726)

• Lipid catabolism

Comparison of triglyceride and carbohydrate as energy stores

Effect of low blood sugar-activation of catabolism

• Effect of low blood sugar of triglyceride stores

Lipolysis, location in fat (and heart muscle), hormone sensitive lipase mediates the rate limiting step

Distribution of the products of lipolysis, role of serum albumin - use of free fatty acid and glycerol by different tissues

Use of glycerol for gluconeogenesis by liver and kidney

Activation of free fatty acids for metabolism-formation of acyl CoA

b-oxidation of even chain fatty acids in mitochondria, acetyl CoA cannot be directly converted into carbohydrate

b-oxidation of odd chain fatty acids - propionyl CoA, methylmalonyl CoA, succinyl CoA - requirement for vitamin B₁₂

b-oxidation of unsaturated fatty acids

b-oxidation of very long chain fatty acids in peroxisomes

Synthesis of ketone bodies-location in liver and kidney mitochondria

Utilization of ketone bodies by brain and muscles

a- and w-oxidation

• Lipid anabolism

Biotin

Accumulation of acetyl CoA in the form of citrate

Regulatory role of acetyl CoA carboxylase, malonyl CoA

Synthesis of palmitate by fatty acid synthase

Elongation of fatty acids

Desaturation of fatty acids

Synthesis of triglyceride

Synthesis of phospholipids - membrane biosynthesis

Synthesis of cholesterol

Amino acid metabolism (Read pp. 727-784, 785-794)

• Protein and amino acid catabolism

Effect of low blood sugar on protein catabolism - a third store of energy

Transaminases, transfer of most a-amino acid N to a-ketoglutarate to give glutamate, Ser to Thr directly deaminated to pyruvate and a-ketobutyrate, asparaginase and glutaminase

Oxidative deamination of glutamate by glutamate dehydrogenase yields energy/reducing power (NADH/NADPH) plus NH₄⁺

Conversion of NH₄⁺ to urea in liver, the urea cycle, location of enzymes, NH₄⁺ and AspNH₂ used to form urea, fumarate, oxaloacetate and a-ketoglutarate link urea formation and the citric acid cycle

Use of carbon skeletons to give energy (and/or glucose in liver and kidney) - ketogenic and glucogenic amino acids

Ala, Ser, Cys, Gly and Thr (glucogenic) give pyruvate

Asp and Asn (glucogenic) give oxaloacetate

Gln, Glu, Pro, Arg and His (glucogenic) give a-ketoglutarate

Leu and Lys (ketogenic) give acetoacetate and/or acetyl CoA

Ile (glucogenic and ketogenic), Val (glucogenic) and Met (glucogenic) give succinyl CoA - requirement for Vit B₁₂

Trp (glucogenic and ketogenic) gives Ala and acetoacetate

Phe and Tyr (glucogenic and ketogenic) give fumarate and acetoacetate, phenylketonuria

Leu, Ile and Val grouped as branched chain amino acids - maple syrup disease

Use of alanine and lactate from muscles for gluconeogenesis in liver (alanine-glucose and Cori cycles)

Utilization of branched chain amino acids in the brain

• Amino acid synthesis

C1 carriers, tetrahydrofolate, S-adenosylmethionine

Essential and non-essential amino acids

Purine and pyrimidine bases, nucleosides, nucleotides (Read pp. 795-828)

• Basic chemistry
• Purine and pyrimidine catabolism
• Purine and pyrimidine biosynthesis - role of 5-phosphoribosyl-1-pyrophosphate (PRPP)

Second Examination - Membranes, lipid metabolism, amino acid metabolism, and nucleotide metabolism
(Thursday 4 May 2000)

Final Comprehensive Examination
Monday 8 May 2000
7:50 to 9:50 a.m.

Biochemistry and Molecular Biology Home Page

For more information or comments about this page contact:
eniederhoffer@siumed.edu