CHAPTER 1 Foundations of Biochemistry

Learning Objectives• Distinguishing features of living organisms• Structure and function of cells and organelles• Roles of small and large biomolecules• Energy transformation in living organisms• Regulation of metabolism and catalysis• Coding of genetic information in DNA• Mutation, selection and evolution• Molecular phylogeny

Biochemistry

Chapter 1:Fundamentals of Biochemistry

What is Biochemistry? In previous classes you have encountered aspects of this subject in

Chemistry and Biology

In this course you will be introduced more complex but exciting concepts in Biochemistry

Biochemists use basic laws of

Chemistry, Biology and Physics to explain?

Processes of living cells

Even though the word Biochemistry has become common place in our language, a concise meaningful definition is difficult

Simplest definition is:

“The chemistry of the living cell”Overall goal of biochemistry is to describe:

“life’s processes at the level of molecules”

Therefore, in order to describe these processes …? One must have a

i. Knowledge of chemical structures of participating molecules (Conformational study)

ii. Understanding of the biological function of cellular molecules (Informational)

iii. study of energy flow is living system ---- (Bioenergetics)

All biological processes including

vision, digestion, thinking, motion, immunity and disease conditions result from the actions of molecules

Physical Science (Chemistry, Physics)

Biological Science

Brief History of Biochemistry

The term molecular biology was first coined in 1938 by Rockefeller Foundation

Biochemistry and molecular biology have similar goals; however, their approaches to solving problems have been different in the past:

Molecular biologists– emphasize the study of genetic materials (RNA and DNA), especially its role in biological information transfer and they use more biological experimental approaches involving organisms, recombinant DNA and molecular genetics

Biochemists– focus on the structure and function of all biomolecules and energy relationships among them.

In fact, most scientists consider the fields to be the same.

Both becoming indistinguishable because they seek answers to the same question: what is life?

Biochemistry- Molecular Biology

Cells: Universal Building Blocks • Living organisms are

made of cells• Simplest living

organisms are singe-celled

• Larger organisms consists many cells with different functions

• Not all the cells are the same

Three Domains of Life

• Differences in cellular and molecular level define three distinct domains of life

Bacterial, Plant, and Animal Cells are Different

• The internal structure and properties of cells from organisms in different kingdoms are rather different but fundamental macromolecules are highly conserved

Structure Composition Function

Cell wall Peptidoglycan Mechanical support

Cell membrane Lipid + protein Permeability barrier

Nucleoid DNA + protein Genetic information

Ribosomes RNA + protein Protein synthesis

Pili Protein Adhesion, conjugation

Flagella Protein Motility

Cytoplasm Aqueous solution Site of metabolism

Components of Bacterial Cell

Eukaryote Cells: More Complexity• Have nucleus by definition

– protection for DNA; site of DNA metabolism– selective import and export via nuclear membrane pores– some cells become anuclear (red blood cells)

• Have membrane-enclosed organelles– Mitochondria for energy in animals, plants and fungi– Chloroplasts for energy in plant– Lysosome for digestion of un-needed molecules

• Spatial separation of energy-yielding and energy consuming reactions helps cells to maintain homeostasis and stay away from equilibrium

Components of Animal Cells

Chemical Composition of Cell

Cytoplasm and Cytoskeleton

• Cytoplasm is highly viscous solution where many reactions take place

• Cytoskeleton consists of microtubules, actin filaments, and intermediate filaments– cell shape– transport paths– movement

Living Systems Extract Energy

• From sunlight– plants– green bacteria– cyanobacteria

• From fuels– animals– most bacteria

• Energy input is needed in order to maintain complex structures and be in a dynamic steady state, away from the equilibrium

Energy and Carbon Sources• All organisms require energy and carbon for life• We can also classify based in the sources of

energy and carbon

Today’s topics

• Elementals of life• Biological molecules• Thermodynamics• Biochemical Reactions• Chemical and Molecular Evolution

Elements of life• Elements H, O, N, P, S are also common• Metal ions (e.g. K+, Na+, Ca++, Mg++, Zn++, Fe++)

play important roles in metabolism• Together, about 30 elements are essential for life

Elemental composition of Life: Unique Role of Carbon

• Biomolecules are carbon-based

Biological Molecules Typically Have Several Functional Groups

Structure of Biological Molecules is Important

• The function of molecules strongly depend on three-dimensional structure

Stereoisomers have Different Biological Properties

• Cis and trans isomers have also different physical and chemical properties

Optical Isomers have Different Biological Properties

• Enantiomers have identical physical properties (except regard to polarized light) and react identically with achiral reagents.

• Diastereomers have different physical and chemical

R = rectus (right-handed)S = sinister (left-handed)

Interactions between Biomolecules are Specific

• Macromolecules have unique binding pockets• Only certain molecules fit in well and can bind• Binding of chiral biomolecules is stereospecific

Thermodynamics -Energetic Driving Forces

G = H – TSFree Energy = Enthalpy – (T × Entropy)

• Spontaneous Chemical Processes are characterized by reduction in Free Energy

Reactants => Products• GProducts – GReactants = ΔG = ΔH – TΔS

• Spontaneous if ΔG is negative

Free Energy

• Every Chemical Compound has a standard Free Energy of Formation G°

• The standard state is typically 1 M, 25°C• For biochemical reactions pH (7.0) is

specified as well • The conversion of 1 mole of:• A + B => C + D• ΔG° = (G°C + G°D ) - (G°A + G°B )

Chemical Equilibrium• A + B <==> C + D

• ΔG = ΔG° + RT ln

• At equilibrium forward and reverse reactions balance, ΔG = 0

• ΔG° = - RT ln Keq

Unfavorable and Favorable Reactions

• Synthesis of complex molecules and many other metabolic reactions requires energy (endergonic)– A reaction might be thermodynamically unfavorable (G° > 0)

• Creating order requires work and energy

• Breakdown of some metabolites releases significant amount of energy (exergonic)– Such metabolites (ATP, NADH, NADPH) can be synthesizes using

the energy from sunlight and fuels– Their cellular concentration is far higher than their equilibrium

concentration.

ATP: Chemical Currency of Energy

Energy Coupling• Chemical coupling of exergonic and endergonic

reactions allows otherwise unfavorable reaction

• The “high-energy” molecule (ATP) reacts directly with the metabolite that needs “activation”

Kinetics – Reaction Rate Acceleration

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

Catalysis

• A catalyst is a compound that increases the rate of a chemical reaction

• Catalysts lower the activation free energy G‡

• Catalysts does not alter G° • Catalysis offers:

– Acceleration under mild conditions– High specificity– Possibility for regulation

Energy Flows through ATP and redox carriers to

couple Catabolic and

Anabolic Pathways

Metabolic Pathwayproduces energy or valuable materials

Signal Transduction Pathwaytransmits information

Series of Related 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

Pathway for the flow of genetic information:DNA → RNA → Protein

DNA stores information

RNA transmits information

Protein function manifests information

The Central “Dogma” of Biochemistry

Genetic and Evolutionary Foundations

• Life on Earth arose 3.5 – 3.8

billion years ago• Formation of self-replicating

molecules a key step• DNA? – Info, Self Template• Proteins? – Function• RNA? – Both

• Evolutionary Evidence is in

DNA sequences TODAY!

RNA World?

• RNA can acts both as the information carrier and biocatalyst

• There is something fascinating about science. One gets such wholesale returns of conjecture out of such a trifling investment of fact.

Evolution of Eukaryotes through Endosymbiosis

Natural SelectionFavors Some Mutations

• DNA replication is amazingly, but not absolutely, error-free

• Mutations occur more or less randomly• Most mutations are “silent”• Many are deleterious• Rare mutations that yield an advantage in a

given environment are more likely to be propagated

Assignment• Define the following terms

– Vital force theory - Enantiomers– Gene and genetic code - Aquaporin– Recombinant DNA - Bioinformatics

• Out of 100 plus chemical elements, only about 31 (28%) occur naturally in plants and animals, How these elements were selected?

• Make a list of Nobel Laureates in Chemistry and Physiology from 2005 to 2013 and enlist their key findings relevant to Biochemistry

Note: prepare hand written assignment on assignment pages

Assignment• What are advanced DNA sequencing techniques, make a

list

• Differentiate between Chemical Reactions and Biochemical Reactions

• What are features of archeae bacteria?

• What do you mean by mycoplasma?

• Differentiate Chemical, Molecular and Biological Evolution

Note: prepare hand written assignment on assignment pages