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:
Introduction to Biochemistry

By: Dr. Sobia Mushtaq

 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 in 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 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
 Components of Bacterial Cell

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
 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 plants
– 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
– It also helps support the organelles, like
the nucleus and mitochondria,
– The cytoskeleton is the "skeleton" of the
cell. ...Cytoplasm is the jelly-like material
found inside all cells. It is mostly water,
and it provides a place for the cells
essential chemical reactions to take
place.
 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
 Further…….

• Elements 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 asymmetric in such a way that the structure
and its mirror image are superimposable
• Diastereomers have different physical and chemical
properties (stereoisomers that are not mirror images of
one another and are non-superimposable on one
another)

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
 Unfavorable and Favorable
Reactions
• Synthesis of complex molecules and many other metabolic
reactions requires energy (endergonic)

• Creating order requires work and energy

• Breakdown of some metabolites releases significant amount

of energy (exergonic)
– Such metabolites (ATP, NADH, NADPH) can be synthesized using
the energy from sunlight and fuels
ATP: Chemical Currency of Energy
 Energy Coupling

• The “high-
energy”
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

• Catalysis offers:
– Acceleration under mild conditions
– High specificity
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
 • Regulates away from active site
Inactive Active Substrate
Enzyme Enzyme Now fits

Positive Active Site

Regulator Changed
Positive regulation - activates the enzyme.
Negative regulation - deactivates the enzyme.
 Inactive Negative
Enzyme Feedback Control
Regulator

E11 End Product

Stops E11

B C D

A
E11 E11 E22 E33
Active
Allosteric
Enzyme
The Central “Dogma” of Biochemistry

Pathway for the flow of genetic information:

DNA → RNA → Protein

DNA stores information

Transcription
RNA transmits information
Translation

Protein function manifests

information
Except for water most of the molecules found in the
cell are lipids or macromolecules and classified
into four categories:

 Lipids
 Carbohydrates
 Proteins
 Nucleic acids

 Each type of macromolecule possesses distinct

chemical properties that suit it for the functions it
serves in the cell.
Macrolmolecules fold into complex three-dimentional
structures:
 Making/breaking covalent linkages
 Rather folding process is dictated by the
i. Primary structure
ii. The way in which different elements of the molecules interact
with each other and water.

Water is the primary factor in determining the type of structures

that forms:
 Major component of living system
 Interact with many biomolecules

 Hydrophilic/hydrophobic/amphipathic
· Good solvent for polar and ionic material such as salts, small
polar molecules (amino acids, sugars, nucleic acids …) and the
exterior of proteins.

· Solubility enhanced for molecules that can form H-bonds i.e.

hydroxy, keto, carboxy, amino groups, and these are termed
hydrophilic (water loving) groups.

· Solubility reduced for molecules that cannot form H-bonds (i.e.

hydrocarbons such as alkanes, alkenes), and these are termed
hydrophobic (water fearing) compounds.
Molecular properties of Water
 The water molecule is bent.
 O (3.5) is more electronegative than H (2.2)
 H2O is highly polar with a net dipole.
 has 33% ionic character.




O O
H
H H H 
104.5oC
 Hydrogen bonding in ice.

Each H2O forms 4 H-bonds.

In liquid water,
each H2O forms, on average,
3.4 H-bonds.

This is why less dense ice

floats in liquid water, and why
water expands when frozen.
Formation of micelles
Not favorable
G > 0
Favorable
G < 0
Hydrophobic Interactions
The pH Scale
1
pH = log
[H+]

= ‒ log [H+]

pH 7 is neutral,
[ H+] = [OH‒]
pH < 7 is acidic,
[ H+] > [OH‒]
pH > 7 is basic,
[OH‒] > [ H+]

pH + pOH = 14
• The pH must be controlled in
an organism; where the breakdown
in pH regulation can lead to serious
metabolic disturbances:
• The pH of blood is normally kept
within 7.35~7.45.
Outside the narrow range, the
organism can not function.
• The pH of the cytosol of most
cells is ~ 7.4, however, in the
lysosomal organelles the pH is ~
5.0. This is the pH at which the
degradative enzymes (proteases)
of the lysosome function best, and
they are actually inactive at
cytosolic pH!
 Negative pH ? YES
Most substances have a pH in the range 0 to 14, although
extremely acidic or extremely basic substances may have pH less
than 0 or greater than 14.

An example is acid mine runoff, with a pH = –3.6

Buffers
A system whose pH changes only slightly when small
amounts of acid or base is added.
 Used to control the pH within a system

How buffer works?

Buffer works because the added H+ or OH‒ ions
are consumed and do not directly affect the pH.
Concepts and types of
Metabolism
 A. Basic Concepts
• Definitions
– Metabolism: The processes of catabolism and
anabolism
– Catabolism: The processes by which a living
organism obtains its energy and raw materials
from nutrients
– Anabolism: The processes by which energy
and raw materials are used to build
macromolecules and cellular structures
(biosynthesis)
Metabolism Relationships
Metabolism Pathways
 A. Basic Concepts

2.Reduction and Oxidation

– An atom becomes more reduced when it
undergoes a chemical reaction in which it
• Gains electrons
• By bonding to a less electronegative atom
• And often this occurs when the atom becomes
bonded to a hydrogen
 A. Basic Concepts
2.Reduction and Oxidation
b)An atom becomes more oxidized when it
undergoes a chemical reaction in which it
• Loses electrons
• By bonding to a more electronegative atom
• And often this occurs when the atom becomes
bonded to an oxygen
2.Reduction and Oxidation
c)In metabolic pathways, we are often
concerned with the oxidation or reduction of
carbon.
d)Reduced forms of carbon (e.g. hydrocarbons,
methane, fats, carbohydrates, alcohols) carry
a great deal of potential chemical energy
stored in their bonds.
e)Oxidized forms of carbon (e.g. ketones,
aldehydes, carboxylic acids, carbon dioxide)
carry very little potential chemical energy in
their bonds.
 A. Basic Concepts
2.Reduction and Oxidation
f) Reduction and oxidation always occur
together. In a reduction-oxidation reaction
(redox reaction), one substance gets reduced,
and another substance gets oxidized. The
thing that gets oxidized is called the electron
donor, and the thing that gets reduced is
called the electron acceptor.
3.Enzymatic Pathways for Metabolism
– Metabolic reactions take place in a step-
wise fashion in which the atoms of the raw
materials are rearranged, often one at a
time, until the formation of the final product
takes place.
– Each step requires its own enzyme.
– The sequence of enzymatically-catalyzed
steps from a starting raw material to final
end products is called an enzymatic
pathway (or metabolic pathway)
4. Cofactors for Redox Reactions

NAD(oxidized) + H+ + Pair of electrons 

NADH(reduced)

FAD(oxidized) + H+ + Pair of electrons 

FADH(reduced)
5. ATP: A “currency of energy” for many cellular
reactions
– ATP stands for adenosine triphosphate. It is a
nucleotide with three phosphate groups linked in a
small chain.
– The last phosphate in the chain can be removed by
hydrolysis (the ATP becomes ADP or adenosine
diphosphate).
This reaction is energetically favorable: it has a DG°' of
about –7.5 kcal/mol
ATP + H2O ® ADP + Phosphate + Energy (7.5
kcal/mol)
Metabolism
Summary