Lecture 1

Introduction

Chapter 1

BCHS 3304: General Biochemistry I - Spring 2012

Section 10637

1:00 - 2:30 PM Mondays / Wednesdays SEC101

Dr. Hye-Jeong YeoPh.D.(Biochemistry): Universit Montpellier II, MontpellierPost-doc (Protein Crystallography): Washington Univ. School of Medicine, St. Louis

Protein Crystallography / Molecular Structural Biology

http://www.bchs.uh.edu/~yeo/ (my research group)http://www.uh.edu/blackboard(course home page)Office: HSC 448 phone 713-743-8377; E-mail hyeo@uh.eduOffice hours: Mondays 2:30 - 3:30 or by appointment3 Exams and a Comprehensive Final (See Syllabus)

Homework-to be COMPLETED but not turned in!!!Three mid-term exams are required!!

Course Instructions:

The Exams are based on the book, class notes, and homework.Those who do the homework honestly and persistently will earnthe better grades.

I encourage group homework and study sections (groups of 3-4 arethe best size). But each person in a group must pull their ownweight. Copying the homework and not fully participating cheatsyourself.

You will need to know the material! You can not just be familiarwith it. You will need to study about 2-3 hours a day! This is anupper-level PROFESSIONAL COURSE.

Most of figures used in these class notes were taken from theinstructor CD provided with the class textbook (Voet, Voet, andPratt). I am not, in any way, taking credit for having created thesefigures!

Answer keys to homework will be placed on the course web site.

500 pts.Total Points Possible for the

Semester

200 pts.May 9

(2 PM - 5 PM)

Comprehensive Final Exam

(required)

100 pts.April 16Exam III

100 pts.March 17Exam II

100 pts.Feb 13Exam I

A: 100-90% A-: 89 - 86%

B+: 85-81% B: 80 -75% B-: 74 - 70%

C+: 69-66% C: 65-60% C-: 59 - 55%

D+: 54-50% D: 49-45%

F: below 44%

The lecture notes

Try to attend every lecture! Chronic lack of attendance willseverely impact your course grade. These notes are not asubstitute for class participation. These notes are posted onthe web, although they may be altered before class. They areintended to make you pay attention in class, so take thesenotes with you. Dont just sit in class and just copy notes!!

I will TRY, but do not promise, to have the course notesavailable on the class web site by 5:00 in the afternoon theday before the lecture is given.

Read the assigned material before the lecture.

Collect Homework 1 and START IT!!!

Foundations of Biochemistry

Chapter 1: Life

Biochemistry is the study of the chemistry of life.Biochemistry is an interdisciplinary science overlapping with

chemistry, cell biology, genetics, immunology, microbiology,pharmacology, and physiology.

Main issues of Biochemistry1. What are the chemical and three-dimensional structures of

biological molecules?2. How do biological molecules interact with each other?3. How does the cell synthesize and degrade biological molecules?4. How is energy conserved and used by the cell?5. What are the mechanisms for organizing biological molecules

and the coordinating of their activities?6. How is genetic information stored, transmitted, and expressed?

The Physical Laws of Life

Living organisms operate within the same physical laws thatapply to physics and chemistry:

Conservation of mass, energy Laws of thermodynamics Laws of chemical kinetics Principles of chemical reactions

Living organisms are composed of lifeless molecules thatconform to the physical laws of nature.

However, the collective behavior of these many molecules andtheir combined interactions yield extraordinary properties.

Molecular Logic of Life

These physical laws describe several axioms that make up theMolecular Logic of Life. These axioms define:

Energy converted to work Catalytic chemical transformations Assembly of molecules with great complexity from simple

subunits. Complex molecules combine to form supra molecular

components, organelles and finally assemble into a cell. Store and pass on instructions for the assembly of all future

generations from simple non-living precursors

Prebiotic World

Living matter consists of a small number of elements (see Table 1-1, p.3) Elemental composition of the human body (98%)

Carbon (C) 61.7%; Nitrogen (N) 11.0%; Oxygen (O) 9.3%Hydrogen (H) 5.7%; Calcium (Ca) 5.0%; Phosphorous (P) 3.3%Potassium (K) 1.3%; Sulfur (S) 1.0%; Chlorine (Cl) 0.7%Sodium (Na) 0.7%; Magnesium (Mg) 0.3%Trace: B, F, Si, V, Cr, Mn, Fe, Co, Cu, Zn, Se, Mo, Sn, I

Most organisms are ca. 70% water

The earth is ca. 4.6 billion years old.

Earliest known fossil is ca. 3.5 billion years old (filamentousbacterium).

Prebiotic World

Early atmosphere probably consisted of H2O, N2, CO2, with smallamounts of CH4, NH3, SO2, and H2

Sparking of a mixture of CH4, NH3, H2O, and H2 for 1 week yielded Acids (formic, glycolic, lactic, propionic, acetic, succinic, aspartic,

glutamic, etc.) Amino acids (glycine, alanine, aspartic, glutamic) Others (urea, sarcosine, N-methyl-alanine, N-methyl-urea, etc.)

The above experiments were meant to mimic the effects oflightening on the prebiotic atmosphere.

Common Functional GroupsArise from simple organic compounds

Organic Functional Groups - you must know these

They will show up time and time again in Biochemistry

Note that the charge state of some of the groups above will be different underphysiological conditions (COOH; COO-)

Many enzymes catalyze hydrolysis andcondensation reactions

In prebiotic times, clay may haveprovided the environment for catalyticreactions

In particular, the condensation reactionhas been very useful throughout evolutionfor increasing biological complexity

Of course, the hydrolysis carries out thereverse reaction, leading to a loss inbiological complexity

Chemical Evolution

Complementarity allows for (self) replication through templating

Base complementarity in DNA is an example of templating

Replication through complementarity

Specific pairing of functionalgroups gives rise tocomplementarity

More complex moleculesincreases chemical versatility

Complementarity makes itpossible for macromolecules toreplicate

Over time natural selectionfavored molecules that madeaccurate copies of themselves

Association of complementary molecules

Replication through complementarity

Vesicles (fluid-filled sacs) are thought to be the precursors to cells

These entities would have had the ability to shield self-replicatingchemical reactions and catalyzed reactions so that they were takingplace in a sheltered environment, giving them a competitiveadvantage

This process is called compartmentation

This compartment then has the opportunity to further evolve inorder to enhance its advantage.

A typical animal cell contains as many as 100,000 different types ofmolecules

A common bacterium, E. coli, contains millions of molecules,representing 3000-6000 different compounds.

Cellular Architecture

E. coli

All modern organisms are based on the same morphological unit,the cell

Prokaryotes lack a nucleus (e.g., bacteria) Eukaryotes membrane enclosed nucleus encapsulating their DNA

Viruses are not cells and are not living since they lack the apparatusto reproduce outside of their host cells

Prokaryotes range in size from 1 to 10 M Eukaryotes range in size from 10 to 100 M and thus have a

thousand to a million times as much volume as a prokaryotic cell

Prokaryotes and Eukaryotes

Representative Prokaryotes

Eukaryotic cell

A typical animal cell

Eukaryotic cell

A typical plant cell

BiologicalLengthScales

Phylogenetic tree

How do organisms evolve?

1. Evolution is not directed toward a particular goal.It proceeds via random changes. Organisms that are better suitedto their environment flourish.

2. Evolution requires some built-in sloppiness.This is the source of the random changes. It allows foradjustment to unforeseen changes in the environment.

3. Evolution is constrained by its past.The new arises from the old.

4. Evolution is ongoing.Not always toward increasing complexity.

What distinguishes living organisms?

1. Structurally complicated and highly organizedproteins, DNA, RNA, starches, and lipids etc. (inanimate objectssand clay are mixtures of simple compounds)

2. Living organisms:

a. extractb. transformc. stored. Use

3. Most characteristic attribute of living things is self-replication andself assembly - it is the quintessence of the living state

1 single bacteria 109 in 24 hr (inanimate matter does not do this)also the near-perfect fidelity of this process is awesome!Life is a set of relationships characterizing the nature, function and

interaction of biomolecules.

EnergyEnergy is needed to build and maintain structures. mechanical energy ---muscles chemical energy --- electric eel light energy --- bioluminescence

Cell multi cell, varied and diverse and evolutionary processeslead to diversity but life has many common themes and processes.

Organic compounds found in living organisms are a product ofBiological Activity

Biomolecules are selected by evolution- the fit are kept, the not fitare discarded.

The more fit remain and continue to evolve.

Physical Units of Space, Time, and Energy.

LENGTH

You must know this and be comfortable using them.Length is very important!!

C - C bond is 1.54 Hemoglobin 65Ribosomes 300Viruses 100 - 1000Cells 7 m or 7 x 104 (70,000 )

1 10 100 1000 104 10510-10m 10-9m 10-8m 10-7m 10-6m 10-5m

Limit of a light microscope = 2000 or 0.2m

1 104 knowledge comes from X-ray crystallography, electronmicroscope or atomic force microscope

Life is in constant fluxSubstrates Products 10-3 sec - milli sec (ms)Unwinding of DNA 10-6 sec - micro sec (s)

10-15 s 10-12 s 10-9 s 10-8 s 10-6 s 10-3 s 10 s 103sfemto pico nano micro milli sec

femto, fs excitation of chlorophyllpico, ps charge separation in photosynthesisnano, ns hinge protein action10-8 (10 ns) fluorescence lifetimemicro, s DNA unwindmilli, ms enzymatic reactions103 s generation of bacteria2.3 x 109 s average human life span

EnergyUltimate source of energy is the sun

E = h 57 kcal/mol of photons green lightor

238.5 kJ/mol1 kcal = 4.184 kJoules

0.239 kcal = 1 kJYou must know how to convert between the two. (We will be using(kJ/mol))ATP energy carrier, for hydrolysis to ADP + Pi= 7.3 kcal/mol or 30.5 kJ/molWhile vibrational energy infrared = 0.6 kcal/mol or 2.5 kJ/mol

C - C bond = 83 kcal/mol or 348 kJ/molthe framework of a carbon skeleton is thermally stable

but

non-covalent bonds are only a few kcal/mol

Thermodynamics First Law

The First Law of Thermodynamics

Energy (U) is conserved it can be neither created nordestroyed

Most biological processes take place under constantpressure (P) and variable volume (V)

The Enthalpy (H) of a process is defined as follows:

H = U + PV H = U + PV (under constant pressure, the volume

will change like the expansion of a gas)

The volume changes in biological processes arepractically negligible so H U

Thermodynamics Second Law

The Second Law of Thermodynamics

Spontaneous processes are characterized by the conversion oforder to disorder

A process is spontaneous if it can occur without the input ofadditional energy from the outside of the system

Entropy (S) is the measure of the degree of disorder in a system

In the system to the right, the firstsystem has higher order than thesecond.

The second is more disordered.

The entropy increases on going fromthe first to the second system.

The change in entropy is measuredby: S = H/T (T=temperature)