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 Yeo
Ph.D.(Biochemistry): Universit Montpellier II, Montpellier Post-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.edu Office hours: Mondays 2:30 - 3:30 or by appointment 3 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 earn the better grades. I encourage group homework and study sections (groups of 3-4 are the best size). But each person in a group must pull their own weight. Copying the homework and not fully participating cheats yourself. You will need to know the material! You can not just be familiar with it. You will need to study about 2-3 hours a day! This is an upper-level PROFESSIONAL COURSE. Most of figures used in these class notes were taken from the instructor CD provided with the class textbook (Voet, Voet, and Pratt). I am not, in any way, taking credit for having created these figures! Answer keys to homework will be placed on the course web site.

Exam I Exam II Exam III Comprehensive Final Exam (required) Total Points Possible for the Semester

Feb 13 March 17 April 16 May 9 (2 PM - 5 PM)

100 pts. 100 pts. 100 pts. 200 pts. 500 pts.

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 will severely impact your course grade. These notes are not a substitute for class participation. These notes are posted on the web, although they may be altered before class. They are intended to make you pay attention in class, so take these notes with you. Dont just sit in class and just copy notes!! I will TRY, but do not promise, to have the course notes available on the class web site by 5:00 in the afternoon the day 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 Biochemistry 1. 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 that apply 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 that conform to the physical laws of nature. However, the collective behavior of these many molecules and their combined interactions yield extraordinary properties.

Molecular Logic of Life These physical laws describe several axioms that make up the Molecular 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 (filamentous bacterium).

Prebiotic World
Early atmosphere probably consisted of H2O, N2, CO2, with small amounts 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 of lightening on the prebiotic atmosphere.

Common Functional Groups

Arise 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 under physiological conditions (COOH; COO-)

Chemical Evolution
Many enzymes catalyze hydrolysis and condensation reactions In prebiotic times, clay may have provided the environment for catalytic reactions In particular, the condensation reaction has been very useful throughout evolution for increasing biological complexity Of course, the hydrolysis carries out the reverse reaction, leading to a loss in biological complexity

Complementarity allows for (self) replication through templating Base complementarity in DNA is an example of templating

Replication through complementarity

Specific pairing of functional groups gives rise to complementarity More complex molecules increases chemical versatility Complementarity makes it possible for macromolecules to replicate Over time natural selection favored molecules that made accurate copies of themselves

Association of complementary molecules

Replication through complementarity

Cellular Architecture
Vesicles (fluid-filled sacs) are thought to be the precursors to cells These entities would have had the ability to shield self-replicating chemical reactions and catalyzed reactions so that they were taking place in a sheltered environment, giving them a competitive advantage This process is called compartmentation This compartment then has the opportunity to further evolve in order to enhance its advantage. A typical animal cell contains as many as 100,000 different types of molecules A common bacterium, E. coli, contains millions of molecules, representing 3000-6000 different compounds.

E. coli

Prokaryotes and Eukaryotes

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 apparatus to 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

Representative Prokaryotes

Eukaryotic cell

A typical animal cell

Eukaryotic cell

A typical plant cell

Biological Length Scales

Phylogenetic tree

How do organisms evolve?

1. Evolution is not directed toward a particular goal. It proceeds via random changes. Organisms that are better suited to their environment flourish. 2. Evolution requires some built-in sloppiness. This is the source of the random changes. It allows for adjustment 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 organized proteins, DNA, RNA, starches, and lipids etc. (inanimate objects sand clay are mixtures of simple compounds) 2. Living organisms: a. extract b. transform Energy c. store d. Use
Energy is needed to build and maintain structures. mechanical energy ---muscles chemical energy --- electric eel light energy --- bioluminescence

3. Most characteristic attribute of living things is self-replication and self 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.

 Cell multi cell, varied and diverse and evolutionary processes lead to diversity but life has many common themes and processes. Organic compounds found in living organisms are a product of Biological Activity Biomolecules are selected by evolution- the fit are kept, the not fit are 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 65 Ribosomes 300 Viruses 100 - 1000 Cells 7 m or 7 x 104 (70,000 ) 1 10-10m 10 10-9m 100 10-8m 1000 10-7m 104 10-6m 105 10-5m

Limit of a light microscope = 2000 or 0.2m 1 104 knowledge comes from X-ray crystallography, electron microscope or atomic force microscope

Life is in constant flux

Substrates Products 10-3 sec - milli sec (ms) Unwinding of DNA 10-6 sec - micro sec (s)

10-15 s femto

10-12 s pico femto, fs pico, ps nano, ns 10-8 (10 ns) micro, s milli, ms 103 s 2.3 x 109 s

10-9 s nano

10-8 s

10-6 s 10-3 s micro milli

10 s sec

103s

excitation of chlorophyll charge separation in photosynthesis hinge protein action fluorescence lifetime DNA unwind enzymatic reactions generation of bacteria average human life span

Energy
Ultimate source of energy is the sun

E = h 57 kcal/mol of photons green light

or 238.5 kJ/mol 1 kcal = 4.184 kJoules 0.239 kcal = 1 kJ You 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/mol While vibrational energy infrared = 0.6 kcal/mol or 2.5 kJ/mol

C - C bond = 83 kcal/mol or 348 kJ/mol

the 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 nor destroyed Most biological processes take place under constant pressure (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 are practically negligible so H U

Thermodynamics Second Law

The Second Law of Thermodynamics Spontaneous processes are characterized by the conversion of order to disorder A process is spontaneous if it can occur without the input of additional 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 first system has higher order than the second. The second is more disordered. The entropy increases on going from the first to the second system. The change in entropy is measured by: S = H/T (T=temperature)