lehninger(sixth edition) ch 01: the foundations of biochemistry

CHAPTER-1

Adopted from Nilsen and cox – Lehninger principles of biochemistry (sixth edition)

Learning Objectives

• Prokaryotic and eukaryotic cell structure and functions of each structure.

• Organic chemical bonds and functional groups.• Stereoisomers and cis-trans conformations.• Basics of Thermodynamics and Chemical Kinetics.• Basics of Catabolism and Anabolism.• Biochemical hierarchy from monomerspolymerscell

structure.• Evolution of cells: endosymbiosis; vertical and horizontal

gene transfer.• Evolution of proteins: orthologs and paralogs.

Prokaryote and Eukaryote Cells

what size you see in a microscope? what’s its volume and how much actin and mitochondria could it hold? how many molecules?

Prokaryotic Cell

calculate the length of DNA in a bacterial cell…here it is all folded up!

Bacterial Cytoplasm Is Full of Molecules

Prokaryotic Cell Envelope

Eukaryotic Cell

Muscle Cells

Eukaryotic Cytoskeleton: Actin (red), Microtubules (green) Surround the Nucleus (blue). Fluorescence Microscopy.

Cytoskeleton Elements

Bacteria also have filaments (actin like) and microtubules to organize their cytoplasm.

Biological Monomers

What to Look For = What’s Important:

Functional Groups: amino, carboxyl, carbonyls (both), alcohol, methyl, phosphate, sulfhydryl, and others.

Covalent Bonds – single, double, triple.

Ionization state, or not.

Solubility

How Monomers are Polymerized

Weak Bonds = H-bonds, Ionic bonds, hydrophobic interactions, van der Waals forces.

The Monomers

Structure to Molecular Hierarchy

Periodic Chart

Carbon Bonding

Carbon Bonding

Geometry of carbon bonding

Common Functional Groups of Biological Molecules

several functional groups in single biomolecule.

Molecular Weight or Mass

Biochemistry uses both Molecular Weight (Mr) or Molecular

Mass (m) in “Daltons”

Carbon has Mr = 12 or m = 12D

Very Small Proteins have a mass of 10,000D = 10kD

Very Large ones have mass of >1million D = 1,000kD

(Titin a muscle protein ~3 million D)

Representation of molecules

Ball-and-stick model

Space-filling modelStructural formula in perspective form

Cis and Trans(Configurations of geometric isomers)

Cis and Trans – Conformational Change

Chirality

Problem 11 is about two pharmacological drugs and fits right in here with chirality and drug dosage.

This is Pasteur Looking at Dried Rabbit Spinal Chord….used as a Rabies Vaccine

Tartaric acid precipitates out of aging wine into two types of crystals that Pastuer separated with tweezers and determined the optical rotation of polarized light.

Chiral Rotation

Rectus (right) Sinister (left)

Rotation by Priorities

Priorities of Some Biochemical Functional Groups

-OCH2 > -OH > -NH2 > -COOH > -CHO > -CH2OH > -CH3 > -H

Interactions between biomolecules are specific

Stereoisomers Have Different Biological Effects

ATP

Thermodynamics You Already Know

Endothermic vs Exothermic

ΔG = ΔH – T ΔS

ΔG is related to the Equilibrium ConstantΔG = G products – G reactants Reactants = Substrates

ΔGo = standard free energy change (we will change this later)

for aA + bB cC + dD

ΔG = ΔGo + RT ln K eq

AAA

: Hexokinase Rxn

How to speed reactions up

Higher temperaturesStability of macromolecules is limiting

Higher concentration of reactantsCostly as more valuable starting material is needed

Change the reaction by coupling to a fast oneUniversally used by living organisms

Lower activation barrier by catalysisUniversally used by living organisms

Metabolic Pathway• produces energy or valuable materials

Signal Transduction Pathway• transmits information

Series of related enzymatically catalyzed reactions forms a pathway

Example of a negative regulation:Product of enzyme 5 inhibits enzyme 1

Pathways are controlled in order to regulate levels of metabolites

Anabolism and Catabolism

Metabolic Diversity

Information Codes

Prism of Sennacherib Bacterial DNA

~700 BC, Assyrian

DNA Replication

Central DogmaDNA code Transcription Translation Protein

A

Miller and Urey Experimentin a Garage,

1953

RNA World to DNA/RNA/Protein

World

Current Year

Endosymbiotic Origin of Mitochondria and Chloroplasts

From Darwin to Orthologous and Paralogous Genes

Paralogous Selection Required Gene Duplication

Things You must have to know• To understand what defines living organisms and how

biochemists isolate cell structures • To know cell structures and their functions• To know the organic structure of biomolecule’s

functional groups and bonds• To grasp principles of bioenergetics and chemical

kinetics• To know basics of catabolism and anabolism and

biochemical hierarchy• To review the forces driving evolution and know the

difference between orthologous and paralogous evolution of proteins.

• To be able to do Problems 1, 3, 5, 8, 11, 12