Welcome to MCB 102!

"Survey of the Principles of Biochemistry & Molecular Biology" Fall, 2012

Biochemistry is essential to understand cell function

DEFINITION

Biochemistry
(also called biological chemistry or physiological chemistry)

The aim of Biochemistry is to obtain a detailed level of mechanistic understanding about all of the molecules and all of the chemical reactions that constitute the life processes that occur in cells and organisms.

DEFINITION

Molecular Biology
Molecular Biology comprises the branch of Biochemistry that is devoted to understanding the formation, structure, and function of biological macromolecules, particularly nucleic acids (DNA and RNA), and processes like chromosome replication, gene transcription, mRNA translation, and genome structure, as well as methods to manipulate ("engineer") these macromolecules.

DEFINITION

Structural Biology
Structural Biology comprises the branch of Biochemistry concerned with elucidating the three-dimensional architecture and dynamics of biological molecules and macromolecular assemblies at atomic resolution, and the physical and chemical principles that dictate biomolecular structure and function.

Course Logistics
Prerequisites: Biol. 1A & Biol. 1AL; Chem. 3A-Chem. 3B Required textbook: Nelson DL, Cox MM (2008) 5th Edition, Lehninger Principles of Biochemistry, W.H. Freeman Co., New York, NY. Required Reading Lecture #1: vii (in Preface); Ch. 1; Ch. 2 bSpace: Syllabus, future reading assignments, special announcements, practice problems, PowerPoint presentations, exam dates, office hours, etc., will be posted. Exam Dates: RECORD & REMEMBER Exam Policies: READ & REMEMBER Discussion Sections: ATTEND ONLY THE DISCUSSION SECTION IN WHICH YOU ARE ENROLLED Reading: DON'T FALL BEHIND, STAY UP TO DATE Problem Sets: DO- My practice problems DO- Practice problems at end of each chapter

Basis of Assessing Student Performance in MCB 102 Three Exams (100 points each) = Five (out of Six) Quizzes (6 points each) = Disc. Session Attendance & Participation = TOTAL 300 pts. 30 pts. 3 pts. 333 pts

Reading for Lecture #1 p. vii in Preface: science, scientist, scientific method Chapter 1: Cellular, chemical, physical, genetic and evolutionary foundations of biochemistry Chapter 2: Water, bonding in aqueous solutions, pH, acid-base properties, buffers These readings are basically a thorough review of things you have already been exposed to in Chem. 1, Chem. 3A-3B, and Biol. 1A, 1AL, to bring everyone up to speed.

Three ways of visualizing the structure of a carbon compound

Structural formula (with stereochemistry)

Ball-and-stick model (in perspective)

Space-filling representation (van der Waals radii shown)

Stereoisomers and Chirality

(Stereoisomers that are mirror images are called "enantiomers")

Unambiguous Assignment of Stereochemistry 4

CH3

1 NH2
COOH

Priorities: OCH3 > OH > NH2 > COOH > CHO > CH2OH > CH3 > H
Group of lowest priority is placed at the back. In which direction do the other three groups proceed in descending priority order? Clockwise (rectus, Latin for 'rightward') or counter-clockwise (sinister, Latin for leftward')? By these rules, this molecule (L-alanine) has the S configuration.

Acid-Base Equilibria, pH, pKa, and the Principle of Buffering

pKa ~ 2 pKa ~ 9

pH 7

Covalent Bonding and Non-Covalent Interactions

UNITY OF LIFE AT THE BIOCHEMICAL LEVEL All cells are composed of the same sets of smallmolecule, mainly carbon-based, building blocks (and only a few other elements, including nitrogen, phosphorus, sulfur, calcium, magnesium, iron, etc.).

Deciphering the composition of a cell is a finite problem

UNITY AT THE BIOCHEMICAL LEVEL All cells use the same Genetic Code (with only a few rare exceptions) and the same mechanism for decoding DNA (mRNA, amino acyl-tRNAs, ribosomes).

Gln Gln

START

UNITY OF LIFE AT THE BIOCHEMICAL LEVEL All cells are constructed with similar successive levels of hierarchical organization.

Levels of Cellular Organization: Top-Down & Bottom-Up

Proteins

Miscellaneous low-MW metabolites 10% Nucleic acids

60%

5% Inorganic ions
3% 6% Glycans

16%

Lipids

Based on data from Alberts B. et al. (2002) Molecular Biology of the Cell, 4th Ed.

FUNCTIONS OF PROTEINS IN CELLS AND TISSUES

Physiological Role Metabolism Energy Production Movement Protein Function Catabolism Anabolism Oxidation ATP Generation Molecular Motors Example Glyceraldehyde 3-P dehydrogenase Aspartate transcarbamoylase Cytochrome c oxidase F1F0-ATPase Dynein Myosin Kinesin Tubulin Actin Vimentin Cadherins Proteoglycans Collagens DNA polymerase UV endonuclease Rad51 protein RNA polymerase II Methionyl-tRNAMet ligase Hemoglobin Transferrin Histidine permease Ca2+-ATPase Voltage-gated potassium channel Aquaporin Phosvitin Zein Insulin Platelet-derived growth factor Enkephalin -Adrenergic receptor Grb2 Mitogen-activated protein kinase Immunoglobulin- Fibrinogen Phycobiliprotein Green fluorescent protein Trypsin Proteasome Hsp70

Architecture

Cytoskeleton

Cell Contacts Mechanical Support Information Flow

Adhesion Endoskeleton Gene replication Gene repair Gene recombination Gene decoding mRNA decoding Oxygen carriers Iron carrier Permeases Ion pumps Ion channels Water channels Egg yolk Plant seeds Peptide hormones Growth factors Neurotransmitters Receptors Adapters Amplifiers Antibodies Clot formation Light-harvesting Coloration Proteolysis Folding

Nutrient Distribution Transmembrane Transport Channels Storage Signaling

Protection

Pigmentation
Degradation Chaperone

UNITY AT THE BIOCHEMICAL LEVEL Conservation of Protein Function: This feature of living systems arises from the fact that all organisms are related to each other at a deeply rooted level because all life on planet Earth arose by the process of evolution.

Could you repair an antique Model T Ford with parts from your Chevrolet Camaro?

NO WAY!

A conserved protein kinase is a master regulator of the eukaryotic cell cycle

Permissive temperature (25C)

Growth & Proliferation

Restrictive temperature (37C)

NO GROWTH

Schizosaccharomyces pombe ("fission yeast")

cdc2ts mutant

+ [pSpcdc2+]

Growth & Proliferation

Growth & Proliferation

+ [pHsCDK1 cDNA]

A conserved transcription factor is a master regulator of eye development

Ey expressed in the eye primodium promotes normal eye development

Drosophila melanogaster wild-type

Fly Ey expressed in the antenna primodium drives development of extra abnormal eyes

Drosophila melanogaster eyeless (ey) mutant

Mouse Pax6 expressed in the antenna primodium also drives development of extra abnormal eyes

Time flies like an arrow, but fruit flies like bananas!

Ectopic eye on antenna

Homology alone is not always a reliable indicator of conservation of function

Four Levels of Structure in Proteins

Primary Structure

Secondary Structure

Tertiary Structure

Quaternary Structure