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”
All biological processes including
vision, digestion, thinking, motion, immunity and disease
conditions result from the actions 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)
Brief History of Biochemistry


Physical Science
(Chemistry, Physics)
Biological Science
Biochemistry- Molecular Biology
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?
Cells: Universal Building Blocks
• Living organisms are
made of cells
• Simplest living
organisms are singecelled
• 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
Components of Bacterial Cell
Structure
Cell wall
Cell membrane
Nucleoid
Ribosomes
Pili
Flagella
Cytoplasm
Composition
Peptidoglycan
Lipid + protein
DNA + protein
RNA + protein
Protein
Protein
Aqueous solution
Function
Mechanical support
Permeability barrier
Genetic information
Protein synthesis
Adhesion, conjugation
Motility
Site of metabolism
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
•
•
•
•
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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 – TS
Free 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 “highenergy”
molecule (ATP)
reacts directly
with the
metabolite that
needs
“activation”
Kinetics – Reaction Rate Acceleration
Higher temperatures
Stability of macromolecules is limiting
Higher concentration of reactants
Costly as more valuable starting material is
needed
Change the reaction by coupling to a fast one
Universally used by living organisms
Lower activation barrier by catalysis
Universally 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
Series of Related Reactions
Forms a Pathway
Metabolic Pathway
produces energy or valuable materials
Signal Transduction Pathway
transmits information
Pathways Are Controlled in Order to
Regulate Levels of Metabolites
Example of a negative regulation:
Product of enzyme 5 inhibits enzyme 1
The Central “Dogma” of Biochemistry
Pathway for the flow of genetic information:
DNA → RNA → Protein
DNA stores information
RNA transmits information
Protein function manifests
information
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 Selection
Favors 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
– Gene and genetic code
– Recombinant DNA
- Enantiomers
- Aquaporin
- 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