5.07. BIOLOGICAL CHEMISTRY

Fall Semester, 2015

Lecture 1

Course Instructors:

Professor Alexander M. Klibanov, klibanov@mit.edu, office hours by appointmentProfessor Alice Y. Ting, ating@mit.edu, office hours by appointment

Teaching Assistants: Lisa S. Cunden (lcunden@mit.edu) Nicholas A. DeLateur (delateur@mit.edu)

Textbook: Voet, Voet & Pratt, Fundamentals of Biochemistry, 3rd (or 4th) edition (“Voet“).

Lectures: Monday, Wednesday, and Friday from 9 to 10 AM in room 4-370.

Recitations (“R”):

R#1 MW 1 (36-372) – Lisa Cunden R#3 TR 10 (36-144) – Nicholas DeLateur R#2 MW 2 (36-372) – Lisa Cunden R#4 TR 11 (36-144) – Nicholas DeLateur

Some sections may be different than those assigned to you by Registrar. If you have not been

assigned a section, just pick one. Recitations start NEXT WEEK.

Expectations:

Exams: There will be three one-hour exams during the term. The exams are closed book,

closed notes; any necessary information will be included at the end of the exam. The dates are in

your syllabus: Monday, October 5; Monday October 26; and Monday, November 23. Please look at

the dates and determine if you have conflicts. Contact us immediately and we wish to make

alternative arrangements. Each exam is worth 100 points.

Final Exam: There will be a three-hour final exam held during the exam period. The exam

will cover the material for the entire semester and it is also closed book, closed notes. In this course

everything builds on the information from the preceding lectures. The final exam is worth 300

points.

Problem Sets: Every week you will be given a problem set. Each problem set is worth 10

points. The main goal of the problem sets is to focus you on important concepts covered in the

lectures and the textbook. A second goal is to help you keep up with the material covered. It is

acceptable (and indeed encouraged) for you to collaborate with your classmate(s) on the problem

sets, but you must not copy another student’s work. Problem sets are due as indicated in your

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syllabus and should be turned right before the lecture (9 AM) the day they are due in 4-370.

Answers to the problem sets will be posted on the web site within one day after the due date.

Relationship between 5.07 and 7.05: These courses offer two perspectives on the same discipline.

5.07 is offered only in the Fall, 7.05 in the Spring. You cannot take both courses for credit.

Computers and other electronic devices may not be used in the class room. They are not needed and

may be distracting to you and those sitting near you. You will be provided with hard copies of the

handouts prior to each lecture; therefore, just bring a pen or a pencil to make additional notes on

them.

Website: All relevant course information (syllabus, announcements, lecture notes, power point

lecture presentations, study materials, problem sets) is available on the 5.07 stellar website:

http://stellar.mit.edu/S/course/5/fa15/5.07/

Lecture materials: You will receive two sets of lecture materials for each lecture. One is lecture

notes containing the corresponding Voet chapters/pages. They will be posted in an electronic form

on our Stellar web site (see above) each Friday to cover all the lectures to be given the following

week. You are strongly encouraged to review the lecture notes before each respective lecture. In

addition, immediately before each lecture you will be given hard copies of the power point slides to

be used during that lecture; just bring a pen or pencil to make additional notes on them. This power

point presentation also will be posted electronically right after each lecture.

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Lecture 1 (Voet, 3rd edn., Chapter 1, 4th edn., Chapter 1)

What is Biochemistry? Chemistry of life (i.e., life at the molecular level).

A. What is Life? The ability to reproduce and to make order from chaos.

How do environmental changes alter the metabolic pathways in the chart below?

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What are the general principles that control these changes to maintain order to suit the organisms

need?

We will return to the chart above over and over again (the TCA cycle, glycolysis,

gluconeogenesis, fatty acid biosynthesis and degradation, the pentose phosphate pathway, and the

respiratory pathway are shaded). While it seems like metabolism is an incredible jungle, it is not.

This is the case even though some 4,000 known metabolic reactions known, each catalyzed by a

distinct enzyme.

B. All known life forms share certain properties. At the level of our studies, all living organisms

(whether animals, fungi, eubacteria, plants, etc.) share many similarities. We will focus on these

similarities.

1. All living organisms have the same morphological unit of life: the cell. Flees and

elephants have similarly sized cells.

Cell interior: Is the living cell a bag of enzymes and nucleic acids? A bacterial cell

magnified 106 fold.

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The crowded interior of the cell looks like a jungle. However, as with metabolism, studies in the past

two decades are revealing amazing organization within what appears to be chaos. How and when

we look and removing redundancy of function is essential to seeing intracellular organization. The

crowdedness also requires one to think critically about the concept of “free” proteins or “free” small

molecules. Disruption or dilution of the cell environment, required for biochemical analysis,

changes all the reaction equilibria. Recent estimates suggest that in the cell macromolecules are

present at concentrations as high as 350 mg/mL and that small molecules are present at up to 300

mM concentrations.

2. The solvent of life is H2O due to its unique properties.

3. All the building blocks in living organisms are the same. All organisms use nucleotides to

make DNA (deoxyribonucleic acids) and RNA (ribonucleic acids). They all use acetyl-CoA to make

fatty acids and triacylglycerols. They all use sugars to make polysaccharides and amino acids to

make proteins (polypeptides). The chemistry of life is conserved.

4. All the vitamins are conserved. Derivatives of vitamins – coenzymes – expand the

repertoire of protein catalysts (enzymes) to make the molecules of life and produce energy necessary

for life.

5. All organisms share the same mechanism of information transfer: DNA is transcribed

into RNA, which is then translated into protein.

6. The energy currency, required to make order out of chaos, is the same in all organisms:

mainly ATP. A 70-kg person makes (and expends) 45 kg of ATP every 24 h. The machinery to

make ATP is conserved among living organisms.

7. Essentially all metabolic reactions in all organisms are catalyzed by enzymes. Key

enzymatic mechanisms are conserved among organisms.

8. Primary (main) metabolic pathways, both biosynthetic (anabolic) and degradative

(catabolic) pathways are also conserved. In 5.07 we will investigate this semester

glycolysis/gluconeogenesis; fatty acid degradation/biosynthesis; the TCA cycle; the respiratory

chain and how the energy provided by reducing equivalents is used to make ATP; and the pentose

phosphate pathway.

C. Pathways are tightly regulated. How do we control if, say, sugars and fatty acids in the cell are

synthesized or degraded? Regulatory mechanisms have also been conserved; however, in general,

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the more complex the organism, the more complex its regulatory mechanisms. We will discuss the

general mechanisms of regulation:

1. Allosteric regulation: small molecules bind outside the site where chemistry occurs in an

enzyme and affect the rate at which the enzyme converts a substrate to a product.

2. Feedback inhibition: an end product of a pathway may bind to the first enzyme in the

pathway to turn the pathway off when too much of the end product is present.

3. Post-translational modification: many activities of enzymes are profoundly affected by

covalently modifying the protein after it is made by the translational process. Enzymes and other

proteins can be phosphorylated, acetylated, hydroxylated, ubiquitinated, methylated, glycosylated,

etc.

4. Hormonal regulation: binding of hormones (extracellular) to receptors in membranes that

transmit information to the cellular interior. Examples encountered will be epinephrine, insulin,

adrenaline, and glucagon.

D. Biological relevance. Why should we care about biochemistry, which encompasses all of the

above topics? Understanding regulation of the “Fed” and the “Fasting” states and how a living

organism switches its metabolism to accommodate these states is central to elucidating chronic

disease mechanisms and hence treating such diseases. Since most diseases are associated with

metabolic mis-regulation, understanding biochemistry plays a central role in dealing with,

alleviating, and reversing, diseased states.

E. Explicit goals of 5.07

1. To introduce you to all of the chemical players of life: their structures and chemistry and,

consequently, function. Remember that “structure begets function”. Without this background, one

cannot understand biochemistry.

2. Since nearly all metabolic reactions are catalyzed by enzymes, to rationalize metabolism

one must understand how enzymes work.

3. To introduce you to the central pathways of metabolism. At first glance, metabolism can

be daunting but you will see that most of biochemistry is made up of a surprisingly small number of

chemical transformations, which in various forms are used again and again. Understanding these

transformations is sufficient to allow us to predict most metabolic interconversions.

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4. Once the metabolic pathways have been introduced, then one needs to understand their

regulation and their integration under different environmental conditions.

F. The path ahead. As one prominent biochemist said, “The more we learn about these complex

systems, the more we realize that our knowledge is dwarfed by our ignorance.” Biochemistry is a

fascinating discipline with deep roots in both basic and applied science … and there still is much to

do.

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