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Biochemistry I (PHA 156)
Lecture 1 – Introduction & Scope of
Biochemistry
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Objectives
• At the end of the lecture the student should be able
to:
– Define biochemistry and state the scope of
biochemistry
– Explain the principles of biochemistry
– State some useful applications of biochemistry
– Explain the organization of life
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Background
• Combination of ‘Bio-’ and ‘chemistry’; Bio means life
• Simply - Biochemistry is the chemistry of life.
– a branch of chemistry concerned with the chemical reactions
occurring in living organism
• It emerged as a distinct discipline around the beginning of the
20th century when scientists combined chemistry, physiology,
and biology to investigate the chemistry of living systems
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Definition #2:
• Biochemistry is the application of chemistry to the
study of biological processes at the cellular and
molecular level
• Overall goal of biochemistry:
a. Studying the structure and behaviour of the complex
molecules found in biological material and
b. the ways these molecules interact to form cells, tissues
and whole organism
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Principal areas of Biochemistry
• …essentially, biochemistry is the study of cells.
o Structure and function of biological macromolecules
o Metabolism – anabolic and catabolic processes
o Molecular Genetics – How life is replicated. Regulation of
protein synthesis
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How Biochemistry impacts you
• Medicine
• Agriculture
• Industrial applications
• Environmental applications
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Principles of Biochemistry = Foundational truths
• Cells are highly organized and constant source of energy
is required to maintain the ordered state.
• Living processes contains thousands of chemical
reactions. Precise regulation and integration of these
reactions are required to maintain life
• Certain important reactions, e.g. Glycolysis, is found in
almost all organisms.
• All organisms use the same type of molecules:
carbohydrates, proteins, lipids & nucleic acids.
• Instructions for growth, reproduction and developments
for each organism is encoded in their DNA
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Review Questions
1. What is Biochemistry?
2. What is the goal of Biochemistry
3. State examples of applications of Biochemistry in the
following fields
i. Medicine
ii. Agriculture
iii. Environmental protection
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Organization of Life
• elements
• simple organic compounds (monomers)
• macromolecules (polymers)
• Supra-molecular structures
• organelles
• cells
• tissues
• organisms
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Cell Structure and Function
• Objectives:
• At the end of the lecture, the student should be able to:
• Define a cell and describe its basic structure
• State the two types of cells and differentiate between
them
• State the organelles found in a eukaryotic cell and their
functions
• State the functions of cells in the human body
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The Cell
• Basic building blocks of life
• Smallest living unit of an organism
• Grow, reproduce, use energy, adapt, respond to their
environment
• Many cannot be seen with the naked eye
• A cell may be an entire organism or it may be one of
billions of cells that make up the organism
• Two types :
1. Prokaryotic Cell
2. Eukaryote Cell
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Comparison between prokaryotic and eukaryotic cells
Characteristic Prokaryotic Eukaryotic
Size Small (1-10um) Large (10-100um)
Cell membrane Rigid cell wall Flexible plasma
membrane
Sub-cellular organelles Absent Distinct organelles found
Nucleus Not well defined; DNA is
found
Nucleus is well defined;
DNA is associated with
histones
Energy Metabolism Mitochondria absent Mitochondria present
Cell division usually fission & no
mitosis
Mitosis
Cytoplasm organelles & cytoskeleton
absent
contain organelles &
cytoskeleton
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Three main parts of a cell
• Description: membranous sacs containing fluid and a
few floating particles
• Different types, sizes and shapes
• A cell consists of three parts: the cell membrane, the
nucleus, and, between the two, the cytoplasm.
• Within the cytoplasm lie intricate arrangements of
fine fibers and hundreds or even thousands of
miniscule but distinct structures called organelles
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Organelles
• Biologically differentiated structures and living materials of Cytoplasm.
• Essential for different bio-synthetic activities of the cell. Include:
1. Cell membrane
2. Endoplasmic reticulum-Rough and smooth
3. Mitochondria
4. Golgi apparatus
5. Centrosome with centrioles
6. Ribosomes (free and attached)
7. Lysosomes
8. Peroxisomes
9. Filaments
10. Microtubules
11. Vesicles
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Non-Organelles
• Protein
• Fat
• Carbohydrate (Glycogen)
• Water
• Inorganic materials
• Pigments like Melanin , lipofuscin
• Cellular Products: Yolk & Secretory granules
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Characteristic Bio-membranes and Organelles
• Plasma Membrane – A lipid/protein/carbohydrate complex,
providing a barrier and containing transport and signalling
systems.
• Nucleus – Double membrane surrounding the chromosomes
and the nucleolus. Pores allow specific communication with
the cytoplasm. The nucleolus is a site for synthesis of RNA
making up the ribosome
• Mitochondrion – Surrounded by a double membrane with a
series of folds called cristae. Functions in energy production
through metabolism. Contains its own DNA, and is believed
to have originated as a captured bacterium.
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Characteristic Bio-membranes and Organelles
• Rough endoplasmic reticulum (RER) – A network of
interconnected membranes forming channels within the cell.
Covered with ribosomes (causing the "rough" appearance) which
are in the process of synthesizing proteins for secretion or
localization in membranes.
• Ribosomes – Protein and RNA complex responsible for protein
synthesis
• Smooth endoplasmic reticulum (SER) – A network of
interconnected membranes forming channels within the cell. A
site for synthesis and metabolism of lipids. Also contains enzymes
for detoxifying chemicals including drugs and pesticides.
• Golgi apparatus – A series of stacked membranes.
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Characteristic Bio-membranes and Organelles
• Vesicles – (small membrane surrounded bags) carry materials
from the RER to the Golgi apparatus. Vesicles move between
the stacks while the proteins are "processed" to a mature form.
Vesicles then carry newly formed membrane and secreted
proteins to their final destinations including secretion or
membrane localization.
• Lysosomes – A membrane bound organelle that is responsible
for degrading proteins and membranes in the cell, and also
helps degrade materials ingested by the cell.
• Vacuoles – Membrane surrounded "bags" that contain water
and storage materials in plants.
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Characteristic Bio-membranes and Organelles
• Peroxisomes or Microbodies – Produce and degrade
hydrogen peroxide, a toxic compound that can be produced
during metabolism.
• Cell wall – Plants have a rigid cell wall in addition to their cell
membranes
• Cytoplasm – enclosed by the plasma membrane, liquid
portion called cytosol and it houses the membranous
organelles.
• Cytoskeleton – Arrays of protein filaments in the cytosol.
Gives the cell its shape and provides basis for movement. E.g.
microtubules and microfilaments
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Functions of a cell
• They provide structure for the body,
• They metabolise nutrients from food and convert those
nutrients into energy
• Cells carry out specialized functions such as carrying
and transport of oxygen (RBCs)
• Cells also contain the body’s hereditary material and
can make copies of themselves
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Molecules of life
Objectives
• At the end of the lecture, the student should be able
to:
– State the primary elemental composition of biological
systems
– Describe the four primary macromolecules and their
monomer units
– Describe the types of biochemical reactions they
undertake
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Chemical composition of living organisms
• All living organisms are composed of matter.
• Matter is composed of elements.
• An element is a substance consisting of a single type
of atom that cannot be broken down to other
substances by chemical reactions.
• About 25 of the 92 natural elements are known to be
essential to life. Eg ???
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Most abundant, essential for all organism: C, N, O, P, S, H
Less abundant, essential for all organisms: Na, Mg, K, Ca, Cl
Trace levels, essential for all organisms: Mn, Fe, Co, Cu, Zn
Trace levels, essential for some organisms: V, Cr, Mo, B, Al, Ga, Sn, Si, As, Se, I
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Naturally Occurring Elements in the Human Body
Element Symbol Percentage of Human Body
Weight
Elements making up about 96% of human body weight
Carbon C 18.5
Hydrogen H 9.5
Oxygen O 65.0
Nitrogen N 3.3
Elements making up about 3.99% of human body weight
Calcium Ca 1.5
Phosphorus P 1.0
Potassium K 0.4
Sulfur S 0.3
Sodium Na 0.2
Chlorine Cl 0.2
Magnesium Mg 0.1
Elements making up less than 0.01% of human body weight (trace elements).
Boron (B), chromium (Cr), cobalt (Co), copper (Cu), fluorine (F), iodine (I), iron (Fe), manganese
(Mn), molybdenum (Mo), selenium (Se), silicon (Si), tin (Sn), vanadium (V), zinc (Zn).
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Chemical Elements of Life
• Just like cells are building blocks of tissues likewise molecules are
building blocks of cells.
• Animal and plant cells contain approximately 10, 000 kinds of
molecules (bio-molecules)
• Biomolecules present in living organisms are composed of six
elements (C, H, O, N, P, S) which make up approximately 95% of the
mass of cell weight
• Human body also consists of ~60% water of cells content by weight.
• Ions like Na+, K+ and Ca+ may account for another 1%
• Most bio-molecules considered to be derived from hydrocarbons.
• The chemical properties of organic bio-molecules are determined by
their functional groups.
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Review Questions
• State the levels by which life is organized
• What are the six elements that important in life?
• What are the building blocks of cells?
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Primary organic compounds
• For the course, you should be concerned with:
o Carbohydrates
o Proteins
o Lipids
o Nucleic acids
• You are expected to learn the structure and function of
these organic compounds
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Polymers and Monomers
• Each of these types of biomolecules are polymers that
are assembled from single units called monomers.
• Each type of macromolecule is an assemblage of a
different type of monomer
• Monomers: are smaller micromolecules that are put
together to make macromolecules.
• Polymers: are those macromolecules that are created
when monomers are synthesized together.
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How do monomers form
polymers?
• Condensation reactions –
loss of a molecule of water
• Hydrolysis – opposite to
condensation; a water
molecule is added
– Requires catalysis
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• Major classes of monomers
1. Amino acids • Building blocks of proteins
• 20 commonly occurring
• Contains amino group and carboxyl
group functional groups (behavioural
properties
• R group (side chains) determines the
chemical properties of each amino acid
• Also determines how the protein folds
and its biological functions
• Individual amino acids in proteins
connected by peptide bond
• Functions as transport proteins,
enzymes, antibodies, cell receptors
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Sugars
• Carbohydrates: most abundant organic molecule found in nature
• Initially synthesized in plants by photosynthesis
• Basic unit is monosaccharides; monosaccharides can form larger
molecules e.g. glycogen, plant starch or cellulose
Functions
• Store energy in the form of starch (photosynthesis in plants) or
glycogen (in animals and humans).
• Provide energy through metabolism pathways and cycles.
• Supply carbon for synthesis of other compounds.
• Form structural components in cells and tissues.
• Intercellular communications
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Fatty acids
• Monocarboxylic acids; contain even number C atoms
• May be saturated (C-C single bonds) or unsaturated (C-C double
bonds)
• Fatty acids are components of several lipid molecules.
• Examples: triacylglycerol, steroids (cholesterol, sex hormones),
fat soluble vitamins.
Functions
• Storage of energy in the form of fat
• Membrane structures
• Insulation (thermal blanket)
• Synthesis of hormones
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Nucleic acids
• Composed of nucleotide chains that
are vital constituents of all living
cells
• Their monomers are called
nucleotides.
• Nucleic acids store and transmit
their genetic information.
• Two types of nucleic acids are
deoxyribonucleic acid (DNA) and
ribonucleic acid (RNA)
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Review Questions???
1. What is Monomer and Polymer?
2. How do Monomers form Polymers?
3. What is Hydrolysis reaction?
4. What are monomers of Nucleic acid, Protein,
Carbohydrate and lipids?
5. Define what is protein, carbohydrate, lipids and
nucleic acid?
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Biochemical Reactions
• Metabolism: total sum of the chemical reaction happening in a
living organism (highly coordinated and purposeful activity)
a. Anabolism- energy requiring biosynthetic pathways
b. Catabolism- degradation of fuel molecules and the production
of energy for cellular function
• All reactions are catalyzed by enzymes. The primary functions
of metabolism are:
a. Acquisition & utilization of energy
b. Synthesis of molecules needed for cell structure and
functioning (i.e. proteins, nucleic acids, lipids, &
carbohydrates)
c. Removal of waste products
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• Thousands of reactions occur in the cell at every
point in time. Although that may sound very large
and complex in a tiny cell:
• The types of reactions are small
• Mechanisms of biochemical reactions are simple
• Reactions of central importance (for energy
production & synthesis and degradation of major cell
components) are relatively few in number
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Frequent reaction encountered in biochemical processes
1. Nucleophilic Substitution
– One atom of group substituted for another
2. Elimination Reactions
– Double bond is formed when atoms in a molecule is
removed
3. Addition Reactions:
– Two molecules combine to form a single product.
– A. Hydration Reactions
– Water added to alkene > alcohol (common addition rxn)
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Frequent reaction encountered in biochemical processes
1. Isomerization Reactions.
– Involve intra-molecular shift of atoms or groups
2. Oxidation-Reduction (redox) Reactions
– Occur when there is a transfer of e- from a donor to an
electron acceptor
3. Hydrolysis reactions
– Cleavage of double bond by water.
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INTERMOLECULAR FORCES
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Objectives
• At the end of the lecture, the student should be able
to:
– State the types of intermolecular forces that are
important to life
– Give examples of the molecules with these
intermolecular forces respectively
– Rank the intermolecular forces from strongest to
weakest
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Intermolecular forces – Importance to life
• Intermolecular forces are the attractive and repulsive
forces that arise between the molecules of a substance.
• These are weak forces that mediate the interactions
between individual molecules of a substance
• Importance to life:
– Intermolecular forces are weak (compared to covalent bond)
but are control for most of the physical and chemical
properties of matter
– For example, different substances melt or boil at different
temperatures because of the strength of intermolecular forces
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Four types of Intermolecular forces important to life
Salt bridges
• Bonds between oppositely charged residues that are
sufficiently close to each other to experience electrostatic
attraction
• They contribute to protein structure and to the specificity of
interaction of proteins with other biomolecules
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Four types of Intermolecular forces important to life
Dipole-Dipole Interactions – Electrostatic interactions
• Attractive forces among molecules with permanent dipole
(polar).
• The partially positive portion of one molecule is attracted to
the partially negative portion of another molecule. –
strongest intermolecular force of atrraction
• Example: Occurs in HCl.
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Four types of Intermolecular forces
Hydrogen bonding
• The dipole–dipole interactions
experienced when H is bonded to
N, O, or F are unusually strong.
• We call these interactions hydrogen
bonds.
• Hydrogen bonds are formed in
proteins and other small peptides
as well as in DNA
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Four types of Intermolecular forces
London Dispersion Forces (van der Waals Forces)
• It operates for a short distance and it is the weakest
force. This kind of force arises due to the movement of
electrons thus creating temporary positive and
negative charged regions.
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Four types of Intermolecular forces
Hydrophobic Interactions
• Attraction of non polar solutes in water; hydrocarbon chains
such as the side chains of some amino acids (eg. Alanine)
• For example, the folding of the tertiary structure in proteins
and the specific double helical structure of DNA.
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The Biochemistry of Water
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Objectives
• At the end of the lecture, the student should be able
to:
– State some medical and biological importance of
water
– Describe the chemistry of water
– State some physical properties of water
– Describe the classes of molecules according to their
solubility
– Explain the ionization of what and define pH
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MEDICAL AND BIOLOGICAL IMPORTANCE
1. Water is present in every cell. It is the medium in which
all cellular events occurs.
2. It is required for enzyme action and for the transport of
solutes in the body.
3. Water aids the folding of biomolecules like proteins,
nucleic acids etc.
4. Semi-fluid nature of the body is due to water.
5. Water regulates body temperature.
6. Water accelerates biochemical reactions by providing
ions.
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Chemistry of Water - Water is polar
• A polar molecule is one in which one end is partially
positive and the other partially negative.
• Oxygen is more electronegative than hydrogen and
exerts a greater pull on the electrons than Hydrogen
• Oxygen thus gains a partial –ve charge, while hydrogen
atoms a partial +ve charge
• This forms a dipole – a polar covalent molecule
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Physical properties of water
• The polar nature of water
gives it many unique
properties
• It is the medium in which
all cellular chemical
reactions occur.
• It is attracted to other polar
molecules and act as the
universal solvent in cells.
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Physical properties of water
• Water molecules also are reactants in many chemical
reactions.
• For example, in the hydrolysis reaction shown water is
splitting sucrose into separate molecules of glucose and
fructose.
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Physical properties of water
• The polar nature of water molecules leads to hydrogen
bonding.
• The hydrogen bonds between water molecules require
a large amount of heat energy to increase the temper­
ature of water (high heat of vaporization)
• Similarly, a large amount of heat must be lost before
water decreases temperature.
• So, by being 70% water, cells are bathed in a solvent
that maintains a more consistent temperature change.
• Thus water has a high heat of capacity
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Summary of Physical properties of Water
• Water is a universal solvent and acts as a medium for
chemical reaction
• Water acts as a reactant in chemical reactions
• Has high specific heat (heat required to raise the
temperature of 1 gm of water)
• High heat of vaporization; many H-bonds must be
broken before water can evaporate.
• Water in a pure state has a neutral pH
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Hydrophilic, hydrophobic and Amphipathic
• Molecules in the body can be classified under one of
three classes
• Hydrophilic (water loving) – molecules that dissolve in
water. These are
• Hydrophobic (water hating) – molecules that do not
dissolve in water. They repel water
• Amphipathic – molecules that are both hydrophilic
and hydrophobic
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Hydrophilic, hydrophobic and Amphipathic
• Polar substances are hydrophilic. They interact with
the charges on water molecules forming a solvation
shell (hydration shell) eg. NaCl
• Non polar molecules are hydrophobic. They interact
with themselves forming structures that exclude water
molecules eg. glycerol
• Amphipathic molecules have portions that are
hydrophilic and interact with water and portions that
are hydrophobic eg. Some lipids such as phospholipid
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Ionization of water
• Water ionizes to release hydrogen ions [H+
] & hydroxyl
ions [OH-
]
• This can be represented by a dissociation constant Ka
as:
• Ka =
• The equation simplifies as:
• [H2O]Ka = [H+
][OH-
]
• Ka = 1.8 x 10-16 M; [H2O] = 55.5M
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• Ionization of water
• (1.8 X 10-16
M)(55.5 M) = [H+
] [OH-
]
• 1.0 X 10-14
M2
= [H+
] [OH-
] = Ka = Kw
• Ka is for acid, there will be a need for the Kb for the [OH-
]hence
the overall designation Kw (ionic product of water)
• If [H+
]=[OH-
] then [H+
] = 1.0 X 10-7
• Pure water has equal concentrations of H+
and OH-
• [H+
]=[OH-
] = 10 -7
M for a neutral solution
• If [H+
]> 10 -7
M, then the solution is acidic
• If [H+
]< 10 -7
M, then the solution is basic
• pH = -log[H+
] – calculations
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Acid-base concepts and Buffer Systems
Objectives:
• The students should be able to:
– Define an acid and base and differentiate between a weak
acid/base and a strong acid/base
– State some importance of acids and bases in biological
systems
– Define pH and describe the pH scale
– Define buffers and name the biological buffer systems
– Describe the mechanism for regulation of acid-base balance
in the human body
– Explain the disturbances of acid-base balance
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Importance of Acids and Base in biological systems
• Acids and bases must be balanced in cells. Cell
chemistry is sensitive to pH changes
• Most of the biochemical reactions taking place in our
body are in a narrow pH range of 7.0 to 7.8. Even a
small change in pH disturbs these processes.
• Digestion in the stomach occurs in an acidic medium
(HCl in gastric juice). Enzymes thus require a specific
pH and changes will affect their activity
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Definitions
• Acid: any proton donor (a molecule that releases a
proton H+ in water).
a. Strong acids: HCl
b. Weak acids: Carbonic acid (H2CO3), Lactic acids and
sodium dihydrogen phosphate (NaH2PO4).
• Base: is a proton acceptor (a substance accept H+
often
with the release of hydroxyl (OH-
) ions).
a. Strong base: Hydroxyl ion (OH-
).
b. Weak base: Bicarbonate (HCO3
-
).
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HYDROGEN ION AND pH:
• Hydrogen ion (H+
) contains only a single proton
(positively charged particle).
• It is the smallest ionic particle, it is highly reactive.
• The normal H+
concentration in the extracellular fluid
(ECF) is 35 to 45 nM/L.
• The pH is another term for H+
concentration that is
generally used nowadays instead of ‘hydrogen ion
concentration’.
• pH is the negative logarithm of H+
ion concentration.
pH = log
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HYDROGEN ION AND pH:
• The pH scale measures how acidic or basic a substance
is; ranges from 0 to 14.
• A pH of 7 is neutral. A pH less than 7 is acidic. A pH
greater than 7 is basic.
• The pH scale is logarithmic and as a result, each whole
pH value below 7 is ten times more acidic than the
next higher value.
• For example, pH 4 is ten times more acidic than pH 5
and 100 times (10 times 10) more acidic than pH 6.
• The same holds true for pH values above 7
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Buffers
• Biological systems use buffers to maintain pH.
• Definition: A buffer is a solution that resists a
significant change in pH upon addition of an acid or a
base.
• Chemically: A buffer is a mixture of a weak acid and its
conjugate base
• Example: Bicarbonate buffer is a mixture of carbonic
acid (the weak acid) and the bicarbonate ion (the
conjugate base): H2CO3 + HCO3
–
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Buffers
• All OH-
or H+
ions added to a buffer are consumed and
the overall [H+
] or pH is not altered
• H2CO3 + HCO3
-
+ H+
fl‡ 2H2CO3
• H2CO3 + HCO3
-
+ OH-
fl‡ 2HCO3
-
+ H2O
• For any weak acid / conjugate base pair, the buffering
range is its pKa +1.
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REGULATION OF ACID-BASE BALANCE
• The body has three different mechanisms to regulate acid-
base status:
1. Acid-base buffer system, which binds free H+
2. Respiratory mechanism, which eliminates CO2
3. Renal mechanism, which excretes H+
and conserves the bases
(HCO3
–
).
• The acid-base buffer system is the fastest one and it reads
the pH within seconds.
• The respiratory mechanism does it in minutes.
• The renal mechanism is slower and it takes few hours to few
days to bring the pH back to normal. This is however, the
most powerful mechanism
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REGULATION OF ACID-BASE BALANCE BY ACID-BASE
BUFFER SYSTEM
• An acid-base buffer system is the combination of a
weak acid (protonated substance) and a base – the salt
(unprotonated substance).
• Types of Buffer Systems:
1. Bicarbonate buffer system.
2. Phosphate buffer system.
3. Protein buffer system
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Bicarbonate Buffer System
• Present in ECF (plasma). HCO3
–
is in the form of salt, i.e.
sodium bicarbonate (NaHCO3).
• Mechanism of action :
– HCl + NaHCO3 – activated when pH falls.
– NaOH + H2CO3 – activated when pH rises
• Importance of bicarbonate buffer system:
– Concentration of HCO3
–
is regulated by kidney and the
concentration of CO2 is regulated by the respiratory system.
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Phosphate Buffer System
• Useful in the intracellular fluid (ICF), in red blood cells or
other cells,
– Phosphate concentration higher in ICF than in ECF.
• Mechanism of action:
– HCl + Na2HPO4
– NaOH + NaH2PO4
• Importance of phosphate buffer system:
– useful in tubular fluids of kidneys.
• The elements of phosphate buffer inside the red blood
cells are in the form of potassium dihydrogen phosphate
(KH2PO4) and dipotassium hydrogen phosphate (K2HPO4).
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Protein Buffer System:
• Present in the blood; both in the plasma and erythrocytes.
• In plasma:
a. C-terminal carboxyl group, N-terminal amino group and side-
chain carboxyl group of glutamic acid.
b. Side-chain amino group of lysine
c. Imidazole group of histidine.
• In erythrocytes (Hemoglobin):
• Hemoglobin has about six times more buffering capacity
than the plasma proteins.
• When a hemoglobin molecule becomes deoxygenated in the
capillaries, it easily binds with H+
, which are released when
CO2 enters the capillaries.
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REGULATION OF ACID-BASE BALANCE BY RESPIRATORY
MECHANISM:
CO2 + H2O → H2CO3 → H+
+ HCO3
–
• Entire reaction is reversed in lungs when CO2 diffuses from
blood into the alveoli of lungs
• When metabolic activities increase, more amount of CO2 is
produced in the tissues and the concentration of H+
increases
as seen above
• Increased H+
concentration increases the pulmonary
ventilation (hyperventilation) by acting through the
chemoreceptors
• Due to hyperventilation, the excess of CO2 is removed from the
body
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• Kidney maintains the acid-
base balance of the body by
the secreting H+
and
retaining HCO3
–
.
REGULATION OF ACID-BASE BALANCE BY RENAL
MECHANISM
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DISTURBANCES OF ACID-BASE STATUS
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DISTURBANCES OF ACID-BASE STATUS – ACIDOSIS
• Condition of reduced pH (increase in H+
concentration)
below normal range.
• Acidosis is produced by:
1. Increase in partial pressure of CO2 in the body fluids
particularly in arterial blood
2. Decrease in HCO3
–
concentration.
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DISTURBANCES OF ACID-BASE STATUS – ALKALOSIS
• Condition of increased pH (decrease in H+
concentration) above the normal range.
• Alkalosis is produced by:
1. Decrease in partial pressure of CO2 in the arterial
blood
2. Increase in HCO3
–
concentration.
31/01/2025 84
DISTURBANCES OF ACID-BASE STATUS – ALKALOSIS
• Arterial blood is controlled by lungs, thus acid-base
disturbances due to change in arterial pCO2 are called
respiratory disturbances
• Disturbances in acid-base status due to change in HCO3
–
concentration are generally called the metabolic
disturbances
• Thus the acid-base disturbances are:
– Respiratory acidosis
– Respiratory alkalosis
– Metabolic acidosis
– Metabolic alkalosis
31/01/2025 85
RESPIRATORY ACIDOSIS
• Acidosis that is caused by alveolar hypoventilation.
• During hypoventilation the lungs fail to expel CO2.
• CO2 accumulates in blood where it reacts with water to
form carbonic acid, which is called respiratory acid.
• Carbonic acid dissociates into H+
and HCO3
–
.
• The increased H+
concentration in blood leads to
decrease in pH and acidosis.
• Normal partial pressure of CO2 in arterial blood is
about 40 mm Hg. When it increases above 60 mm Hg
acidosis occurs.
31/01/2025 86
RESPIRATORY ALKALOSIS
• Alkalosis that is caused by alveolar hyperventilation.
• Hyperventilation causes excess loss of CO2 from the
body.
• Loss of CO2 leads to decreased formation of carbonic
acid and decreased release of H+
.
• Decreased H+
concentration increases the pH leading
to respiratory alkalosis.
• When the partial pressure of CO2 in arterial blood
decreases below 20 mm Hg, alkalosis occurs
31/01/2025 87
METABOLIC ACIDOSIS
• Acid-base imbalance characterized by excess
accumulation of organic acids in the body, which is
caused by abnormal metabolic processes.
• Organic acids such as lactic acid, ketoacids and uric
acid are formed by normal metabolism
• The quantity of these acids increases due to
abnormality in the metabolism
31/01/2025 88
METABOLIC ALKALOSIS:
• Metabolic alkalosis is the acid-base imbalance caused
by loss of excess H+
resulting in increased HCO3
–
concentration.
• Some of the endocrine disorders, renal tubular
disorders, etc. cause metabolic disorders leading to
loss of H+
.
• It increases HCO3
–
and pH in the body leading to
metabolic alkalosis

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BCHEM 156 - Introduction and Scope of Biochemistry

  • 1. Biochemistry I (PHA 156) Lecture 1 – Introduction & Scope of Biochemistry
  • 2. 31/01/2025 2 Objectives • At the end of the lecture the student should be able to: – Define biochemistry and state the scope of biochemistry – Explain the principles of biochemistry – State some useful applications of biochemistry – Explain the organization of life
  • 3. 31/01/2025 3 Background • Combination of ‘Bio-’ and ‘chemistry’; Bio means life • Simply - Biochemistry is the chemistry of life. – a branch of chemistry concerned with the chemical reactions occurring in living organism • It emerged as a distinct discipline around the beginning of the 20th century when scientists combined chemistry, physiology, and biology to investigate the chemistry of living systems
  • 4. 31/01/2025 4 Definition #2: • Biochemistry is the application of chemistry to the study of biological processes at the cellular and molecular level • Overall goal of biochemistry: a. Studying the structure and behaviour of the complex molecules found in biological material and b. the ways these molecules interact to form cells, tissues and whole organism
  • 5. 31/01/2025 5 Principal areas of Biochemistry • …essentially, biochemistry is the study of cells. o Structure and function of biological macromolecules o Metabolism – anabolic and catabolic processes o Molecular Genetics – How life is replicated. Regulation of protein synthesis
  • 6. 31/01/2025 6 How Biochemistry impacts you • Medicine • Agriculture • Industrial applications • Environmental applications
  • 7. 31/01/2025 7 Principles of Biochemistry = Foundational truths • Cells are highly organized and constant source of energy is required to maintain the ordered state. • Living processes contains thousands of chemical reactions. Precise regulation and integration of these reactions are required to maintain life • Certain important reactions, e.g. Glycolysis, is found in almost all organisms. • All organisms use the same type of molecules: carbohydrates, proteins, lipids & nucleic acids. • Instructions for growth, reproduction and developments for each organism is encoded in their DNA
  • 8. 31/01/2025 8 Review Questions 1. What is Biochemistry? 2. What is the goal of Biochemistry 3. State examples of applications of Biochemistry in the following fields i. Medicine ii. Agriculture iii. Environmental protection
  • 9. 31/01/2025 9 Organization of Life • elements • simple organic compounds (monomers) • macromolecules (polymers) • Supra-molecular structures • organelles • cells • tissues • organisms
  • 10. 31/01/2025 10 Cell Structure and Function • Objectives: • At the end of the lecture, the student should be able to: • Define a cell and describe its basic structure • State the two types of cells and differentiate between them • State the organelles found in a eukaryotic cell and their functions • State the functions of cells in the human body
  • 11. 31/01/2025 11 The Cell • Basic building blocks of life • Smallest living unit of an organism • Grow, reproduce, use energy, adapt, respond to their environment • Many cannot be seen with the naked eye • A cell may be an entire organism or it may be one of billions of cells that make up the organism • Two types : 1. Prokaryotic Cell 2. Eukaryote Cell
  • 13. 31/01/2025 13 Comparison between prokaryotic and eukaryotic cells Characteristic Prokaryotic Eukaryotic Size Small (1-10um) Large (10-100um) Cell membrane Rigid cell wall Flexible plasma membrane Sub-cellular organelles Absent Distinct organelles found Nucleus Not well defined; DNA is found Nucleus is well defined; DNA is associated with histones Energy Metabolism Mitochondria absent Mitochondria present Cell division usually fission & no mitosis Mitosis Cytoplasm organelles & cytoskeleton absent contain organelles & cytoskeleton
  • 14. 31/01/2025 14 Three main parts of a cell • Description: membranous sacs containing fluid and a few floating particles • Different types, sizes and shapes • A cell consists of three parts: the cell membrane, the nucleus, and, between the two, the cytoplasm. • Within the cytoplasm lie intricate arrangements of fine fibers and hundreds or even thousands of miniscule but distinct structures called organelles
  • 15. 31/01/2025 15 Organelles • Biologically differentiated structures and living materials of Cytoplasm. • Essential for different bio-synthetic activities of the cell. Include: 1. Cell membrane 2. Endoplasmic reticulum-Rough and smooth 3. Mitochondria 4. Golgi apparatus 5. Centrosome with centrioles 6. Ribosomes (free and attached) 7. Lysosomes 8. Peroxisomes 9. Filaments 10. Microtubules 11. Vesicles
  • 16. 31/01/2025 16 Non-Organelles • Protein • Fat • Carbohydrate (Glycogen) • Water • Inorganic materials • Pigments like Melanin , lipofuscin • Cellular Products: Yolk & Secretory granules
  • 17. 31/01/2025 17 Characteristic Bio-membranes and Organelles • Plasma Membrane – A lipid/protein/carbohydrate complex, providing a barrier and containing transport and signalling systems. • Nucleus – Double membrane surrounding the chromosomes and the nucleolus. Pores allow specific communication with the cytoplasm. The nucleolus is a site for synthesis of RNA making up the ribosome • Mitochondrion – Surrounded by a double membrane with a series of folds called cristae. Functions in energy production through metabolism. Contains its own DNA, and is believed to have originated as a captured bacterium.
  • 18. 31/01/2025 18 Characteristic Bio-membranes and Organelles • Rough endoplasmic reticulum (RER) – A network of interconnected membranes forming channels within the cell. Covered with ribosomes (causing the "rough" appearance) which are in the process of synthesizing proteins for secretion or localization in membranes. • Ribosomes – Protein and RNA complex responsible for protein synthesis • Smooth endoplasmic reticulum (SER) – A network of interconnected membranes forming channels within the cell. A site for synthesis and metabolism of lipids. Also contains enzymes for detoxifying chemicals including drugs and pesticides. • Golgi apparatus – A series of stacked membranes.
  • 19. 31/01/2025 19 Characteristic Bio-membranes and Organelles • Vesicles – (small membrane surrounded bags) carry materials from the RER to the Golgi apparatus. Vesicles move between the stacks while the proteins are "processed" to a mature form. Vesicles then carry newly formed membrane and secreted proteins to their final destinations including secretion or membrane localization. • Lysosomes – A membrane bound organelle that is responsible for degrading proteins and membranes in the cell, and also helps degrade materials ingested by the cell. • Vacuoles – Membrane surrounded "bags" that contain water and storage materials in plants.
  • 20. 31/01/2025 20 Characteristic Bio-membranes and Organelles • Peroxisomes or Microbodies – Produce and degrade hydrogen peroxide, a toxic compound that can be produced during metabolism. • Cell wall – Plants have a rigid cell wall in addition to their cell membranes • Cytoplasm – enclosed by the plasma membrane, liquid portion called cytosol and it houses the membranous organelles. • Cytoskeleton – Arrays of protein filaments in the cytosol. Gives the cell its shape and provides basis for movement. E.g. microtubules and microfilaments
  • 21. 31/01/2025 21 Functions of a cell • They provide structure for the body, • They metabolise nutrients from food and convert those nutrients into energy • Cells carry out specialized functions such as carrying and transport of oxygen (RBCs) • Cells also contain the body’s hereditary material and can make copies of themselves
  • 22. 31/01/2025 22 Molecules of life Objectives • At the end of the lecture, the student should be able to: – State the primary elemental composition of biological systems – Describe the four primary macromolecules and their monomer units – Describe the types of biochemical reactions they undertake
  • 23. 31/01/2025 23 Chemical composition of living organisms • All living organisms are composed of matter. • Matter is composed of elements. • An element is a substance consisting of a single type of atom that cannot be broken down to other substances by chemical reactions. • About 25 of the 92 natural elements are known to be essential to life. Eg ???
  • 24. 31/01/2025 24 Most abundant, essential for all organism: C, N, O, P, S, H Less abundant, essential for all organisms: Na, Mg, K, Ca, Cl Trace levels, essential for all organisms: Mn, Fe, Co, Cu, Zn Trace levels, essential for some organisms: V, Cr, Mo, B, Al, Ga, Sn, Si, As, Se, I
  • 25. 31/01/2025 25 Naturally Occurring Elements in the Human Body Element Symbol Percentage of Human Body Weight Elements making up about 96% of human body weight Carbon C 18.5 Hydrogen H 9.5 Oxygen O 65.0 Nitrogen N 3.3 Elements making up about 3.99% of human body weight Calcium Ca 1.5 Phosphorus P 1.0 Potassium K 0.4 Sulfur S 0.3 Sodium Na 0.2 Chlorine Cl 0.2 Magnesium Mg 0.1 Elements making up less than 0.01% of human body weight (trace elements). Boron (B), chromium (Cr), cobalt (Co), copper (Cu), fluorine (F), iodine (I), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), silicon (Si), tin (Sn), vanadium (V), zinc (Zn).
  • 26. 31/01/2025 26 Chemical Elements of Life • Just like cells are building blocks of tissues likewise molecules are building blocks of cells. • Animal and plant cells contain approximately 10, 000 kinds of molecules (bio-molecules) • Biomolecules present in living organisms are composed of six elements (C, H, O, N, P, S) which make up approximately 95% of the mass of cell weight • Human body also consists of ~60% water of cells content by weight. • Ions like Na+, K+ and Ca+ may account for another 1% • Most bio-molecules considered to be derived from hydrocarbons. • The chemical properties of organic bio-molecules are determined by their functional groups.
  • 28. 31/01/2025 28 Review Questions • State the levels by which life is organized • What are the six elements that important in life? • What are the building blocks of cells?
  • 29. 31/01/2025 29 Primary organic compounds • For the course, you should be concerned with: o Carbohydrates o Proteins o Lipids o Nucleic acids • You are expected to learn the structure and function of these organic compounds
  • 30. 31/01/2025 30 Polymers and Monomers • Each of these types of biomolecules are polymers that are assembled from single units called monomers. • Each type of macromolecule is an assemblage of a different type of monomer • Monomers: are smaller micromolecules that are put together to make macromolecules. • Polymers: are those macromolecules that are created when monomers are synthesized together.
  • 31. 31/01/2025 31 How do monomers form polymers? • Condensation reactions – loss of a molecule of water • Hydrolysis – opposite to condensation; a water molecule is added – Requires catalysis
  • 32. 31/01/2025 32 • Major classes of monomers 1. Amino acids • Building blocks of proteins • 20 commonly occurring • Contains amino group and carboxyl group functional groups (behavioural properties • R group (side chains) determines the chemical properties of each amino acid • Also determines how the protein folds and its biological functions • Individual amino acids in proteins connected by peptide bond • Functions as transport proteins, enzymes, antibodies, cell receptors
  • 33. 31/01/2025 33 Sugars • Carbohydrates: most abundant organic molecule found in nature • Initially synthesized in plants by photosynthesis • Basic unit is monosaccharides; monosaccharides can form larger molecules e.g. glycogen, plant starch or cellulose Functions • Store energy in the form of starch (photosynthesis in plants) or glycogen (in animals and humans). • Provide energy through metabolism pathways and cycles. • Supply carbon for synthesis of other compounds. • Form structural components in cells and tissues. • Intercellular communications
  • 35. 31/01/2025 35 Fatty acids • Monocarboxylic acids; contain even number C atoms • May be saturated (C-C single bonds) or unsaturated (C-C double bonds) • Fatty acids are components of several lipid molecules. • Examples: triacylglycerol, steroids (cholesterol, sex hormones), fat soluble vitamins. Functions • Storage of energy in the form of fat • Membrane structures • Insulation (thermal blanket) • Synthesis of hormones
  • 37. 31/01/2025 37 Nucleic acids • Composed of nucleotide chains that are vital constituents of all living cells • Their monomers are called nucleotides. • Nucleic acids store and transmit their genetic information. • Two types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)
  • 38. 31/01/2025 38 Review Questions??? 1. What is Monomer and Polymer? 2. How do Monomers form Polymers? 3. What is Hydrolysis reaction? 4. What are monomers of Nucleic acid, Protein, Carbohydrate and lipids? 5. Define what is protein, carbohydrate, lipids and nucleic acid?
  • 39. 31/01/2025 39 Biochemical Reactions • Metabolism: total sum of the chemical reaction happening in a living organism (highly coordinated and purposeful activity) a. Anabolism- energy requiring biosynthetic pathways b. Catabolism- degradation of fuel molecules and the production of energy for cellular function • All reactions are catalyzed by enzymes. The primary functions of metabolism are: a. Acquisition & utilization of energy b. Synthesis of molecules needed for cell structure and functioning (i.e. proteins, nucleic acids, lipids, & carbohydrates) c. Removal of waste products
  • 40. 31/01/2025 40 • Thousands of reactions occur in the cell at every point in time. Although that may sound very large and complex in a tiny cell: • The types of reactions are small • Mechanisms of biochemical reactions are simple • Reactions of central importance (for energy production & synthesis and degradation of major cell components) are relatively few in number
  • 41. 31/01/2025 41 Frequent reaction encountered in biochemical processes 1. Nucleophilic Substitution – One atom of group substituted for another 2. Elimination Reactions – Double bond is formed when atoms in a molecule is removed 3. Addition Reactions: – Two molecules combine to form a single product. – A. Hydration Reactions – Water added to alkene > alcohol (common addition rxn)
  • 42. 31/01/2025 42 Frequent reaction encountered in biochemical processes 1. Isomerization Reactions. – Involve intra-molecular shift of atoms or groups 2. Oxidation-Reduction (redox) Reactions – Occur when there is a transfer of e- from a donor to an electron acceptor 3. Hydrolysis reactions – Cleavage of double bond by water.
  • 44. 31/01/2025 44 Objectives • At the end of the lecture, the student should be able to: – State the types of intermolecular forces that are important to life – Give examples of the molecules with these intermolecular forces respectively – Rank the intermolecular forces from strongest to weakest
  • 45. 31/01/2025 45 Intermolecular forces – Importance to life • Intermolecular forces are the attractive and repulsive forces that arise between the molecules of a substance. • These are weak forces that mediate the interactions between individual molecules of a substance • Importance to life: – Intermolecular forces are weak (compared to covalent bond) but are control for most of the physical and chemical properties of matter – For example, different substances melt or boil at different temperatures because of the strength of intermolecular forces
  • 46. 31/01/2025 46 Four types of Intermolecular forces important to life Salt bridges • Bonds between oppositely charged residues that are sufficiently close to each other to experience electrostatic attraction • They contribute to protein structure and to the specificity of interaction of proteins with other biomolecules
  • 47. 31/01/2025 47 Four types of Intermolecular forces important to life Dipole-Dipole Interactions – Electrostatic interactions • Attractive forces among molecules with permanent dipole (polar). • The partially positive portion of one molecule is attracted to the partially negative portion of another molecule. – strongest intermolecular force of atrraction • Example: Occurs in HCl.
  • 48. 31/01/2025 48 Four types of Intermolecular forces Hydrogen bonding • The dipole–dipole interactions experienced when H is bonded to N, O, or F are unusually strong. • We call these interactions hydrogen bonds. • Hydrogen bonds are formed in proteins and other small peptides as well as in DNA
  • 49. 31/01/2025 49 Four types of Intermolecular forces London Dispersion Forces (van der Waals Forces) • It operates for a short distance and it is the weakest force. This kind of force arises due to the movement of electrons thus creating temporary positive and negative charged regions.
  • 50. 31/01/2025 50 Four types of Intermolecular forces Hydrophobic Interactions • Attraction of non polar solutes in water; hydrocarbon chains such as the side chains of some amino acids (eg. Alanine) • For example, the folding of the tertiary structure in proteins and the specific double helical structure of DNA.
  • 52. 31/01/2025 52 Objectives • At the end of the lecture, the student should be able to: – State some medical and biological importance of water – Describe the chemistry of water – State some physical properties of water – Describe the classes of molecules according to their solubility – Explain the ionization of what and define pH
  • 53. 31/01/2025 53 MEDICAL AND BIOLOGICAL IMPORTANCE 1. Water is present in every cell. It is the medium in which all cellular events occurs. 2. It is required for enzyme action and for the transport of solutes in the body. 3. Water aids the folding of biomolecules like proteins, nucleic acids etc. 4. Semi-fluid nature of the body is due to water. 5. Water regulates body temperature. 6. Water accelerates biochemical reactions by providing ions.
  • 54. 31/01/2025 54 Chemistry of Water - Water is polar • A polar molecule is one in which one end is partially positive and the other partially negative. • Oxygen is more electronegative than hydrogen and exerts a greater pull on the electrons than Hydrogen • Oxygen thus gains a partial –ve charge, while hydrogen atoms a partial +ve charge • This forms a dipole – a polar covalent molecule
  • 55. 31/01/2025 55 Physical properties of water • The polar nature of water gives it many unique properties • It is the medium in which all cellular chemical reactions occur. • It is attracted to other polar molecules and act as the universal solvent in cells.
  • 56. 31/01/2025 56 Physical properties of water • Water molecules also are reactants in many chemical reactions. • For example, in the hydrolysis reaction shown water is splitting sucrose into separate molecules of glucose and fructose.
  • 57. 31/01/2025 57 Physical properties of water • The polar nature of water molecules leads to hydrogen bonding. • The hydrogen bonds between water molecules require a large amount of heat energy to increase the temper­ ature of water (high heat of vaporization) • Similarly, a large amount of heat must be lost before water decreases temperature. • So, by being 70% water, cells are bathed in a solvent that maintains a more consistent temperature change. • Thus water has a high heat of capacity
  • 58. 31/01/2025 58 Summary of Physical properties of Water • Water is a universal solvent and acts as a medium for chemical reaction • Water acts as a reactant in chemical reactions • Has high specific heat (heat required to raise the temperature of 1 gm of water) • High heat of vaporization; many H-bonds must be broken before water can evaporate. • Water in a pure state has a neutral pH
  • 59. 31/01/2025 59 Hydrophilic, hydrophobic and Amphipathic • Molecules in the body can be classified under one of three classes • Hydrophilic (water loving) – molecules that dissolve in water. These are • Hydrophobic (water hating) – molecules that do not dissolve in water. They repel water • Amphipathic – molecules that are both hydrophilic and hydrophobic
  • 60. 31/01/2025 60 Hydrophilic, hydrophobic and Amphipathic • Polar substances are hydrophilic. They interact with the charges on water molecules forming a solvation shell (hydration shell) eg. NaCl • Non polar molecules are hydrophobic. They interact with themselves forming structures that exclude water molecules eg. glycerol • Amphipathic molecules have portions that are hydrophilic and interact with water and portions that are hydrophobic eg. Some lipids such as phospholipid
  • 62. 31/01/2025 62 Ionization of water • Water ionizes to release hydrogen ions [H+ ] & hydroxyl ions [OH- ] • This can be represented by a dissociation constant Ka as: • Ka = • The equation simplifies as: • [H2O]Ka = [H+ ][OH- ] • Ka = 1.8 x 10-16 M; [H2O] = 55.5M
  • 63. 31/01/2025 63 • Ionization of water • (1.8 X 10-16 M)(55.5 M) = [H+ ] [OH- ] • 1.0 X 10-14 M2 = [H+ ] [OH- ] = Ka = Kw • Ka is for acid, there will be a need for the Kb for the [OH- ]hence the overall designation Kw (ionic product of water) • If [H+ ]=[OH- ] then [H+ ] = 1.0 X 10-7 • Pure water has equal concentrations of H+ and OH- • [H+ ]=[OH- ] = 10 -7 M for a neutral solution • If [H+ ]> 10 -7 M, then the solution is acidic • If [H+ ]< 10 -7 M, then the solution is basic • pH = -log[H+ ] – calculations
  • 64. 31/01/2025 64 Acid-base concepts and Buffer Systems Objectives: • The students should be able to: – Define an acid and base and differentiate between a weak acid/base and a strong acid/base – State some importance of acids and bases in biological systems – Define pH and describe the pH scale – Define buffers and name the biological buffer systems – Describe the mechanism for regulation of acid-base balance in the human body – Explain the disturbances of acid-base balance
  • 65. 31/01/2025 65 Importance of Acids and Base in biological systems • Acids and bases must be balanced in cells. Cell chemistry is sensitive to pH changes • Most of the biochemical reactions taking place in our body are in a narrow pH range of 7.0 to 7.8. Even a small change in pH disturbs these processes. • Digestion in the stomach occurs in an acidic medium (HCl in gastric juice). Enzymes thus require a specific pH and changes will affect their activity
  • 66. 31/01/2025 66 Definitions • Acid: any proton donor (a molecule that releases a proton H+ in water). a. Strong acids: HCl b. Weak acids: Carbonic acid (H2CO3), Lactic acids and sodium dihydrogen phosphate (NaH2PO4). • Base: is a proton acceptor (a substance accept H+ often with the release of hydroxyl (OH- ) ions). a. Strong base: Hydroxyl ion (OH- ). b. Weak base: Bicarbonate (HCO3 - ).
  • 68. 31/01/2025 68 HYDROGEN ION AND pH: • Hydrogen ion (H+ ) contains only a single proton (positively charged particle). • It is the smallest ionic particle, it is highly reactive. • The normal H+ concentration in the extracellular fluid (ECF) is 35 to 45 nM/L. • The pH is another term for H+ concentration that is generally used nowadays instead of ‘hydrogen ion concentration’. • pH is the negative logarithm of H+ ion concentration. pH = log
  • 69. 31/01/2025 69 HYDROGEN ION AND pH: • The pH scale measures how acidic or basic a substance is; ranges from 0 to 14. • A pH of 7 is neutral. A pH less than 7 is acidic. A pH greater than 7 is basic. • The pH scale is logarithmic and as a result, each whole pH value below 7 is ten times more acidic than the next higher value. • For example, pH 4 is ten times more acidic than pH 5 and 100 times (10 times 10) more acidic than pH 6. • The same holds true for pH values above 7
  • 71. 31/01/2025 71 Buffers • Biological systems use buffers to maintain pH. • Definition: A buffer is a solution that resists a significant change in pH upon addition of an acid or a base. • Chemically: A buffer is a mixture of a weak acid and its conjugate base • Example: Bicarbonate buffer is a mixture of carbonic acid (the weak acid) and the bicarbonate ion (the conjugate base): H2CO3 + HCO3 –
  • 72. 31/01/2025 72 Buffers • All OH- or H+ ions added to a buffer are consumed and the overall [H+ ] or pH is not altered • H2CO3 + HCO3 - + H+ fl‡ 2H2CO3 • H2CO3 + HCO3 - + OH- fl‡ 2HCO3 - + H2O • For any weak acid / conjugate base pair, the buffering range is its pKa +1.
  • 73. 31/01/2025 73 REGULATION OF ACID-BASE BALANCE • The body has three different mechanisms to regulate acid- base status: 1. Acid-base buffer system, which binds free H+ 2. Respiratory mechanism, which eliminates CO2 3. Renal mechanism, which excretes H+ and conserves the bases (HCO3 – ). • The acid-base buffer system is the fastest one and it reads the pH within seconds. • The respiratory mechanism does it in minutes. • The renal mechanism is slower and it takes few hours to few days to bring the pH back to normal. This is however, the most powerful mechanism
  • 74. 31/01/2025 74 REGULATION OF ACID-BASE BALANCE BY ACID-BASE BUFFER SYSTEM • An acid-base buffer system is the combination of a weak acid (protonated substance) and a base – the salt (unprotonated substance). • Types of Buffer Systems: 1. Bicarbonate buffer system. 2. Phosphate buffer system. 3. Protein buffer system
  • 75. 31/01/2025 75 Bicarbonate Buffer System • Present in ECF (plasma). HCO3 – is in the form of salt, i.e. sodium bicarbonate (NaHCO3). • Mechanism of action : – HCl + NaHCO3 – activated when pH falls. – NaOH + H2CO3 – activated when pH rises • Importance of bicarbonate buffer system: – Concentration of HCO3 – is regulated by kidney and the concentration of CO2 is regulated by the respiratory system.
  • 76. 31/01/2025 76 Phosphate Buffer System • Useful in the intracellular fluid (ICF), in red blood cells or other cells, – Phosphate concentration higher in ICF than in ECF. • Mechanism of action: – HCl + Na2HPO4 – NaOH + NaH2PO4 • Importance of phosphate buffer system: – useful in tubular fluids of kidneys. • The elements of phosphate buffer inside the red blood cells are in the form of potassium dihydrogen phosphate (KH2PO4) and dipotassium hydrogen phosphate (K2HPO4).
  • 77. 31/01/2025 77 Protein Buffer System: • Present in the blood; both in the plasma and erythrocytes. • In plasma: a. C-terminal carboxyl group, N-terminal amino group and side- chain carboxyl group of glutamic acid. b. Side-chain amino group of lysine c. Imidazole group of histidine. • In erythrocytes (Hemoglobin): • Hemoglobin has about six times more buffering capacity than the plasma proteins. • When a hemoglobin molecule becomes deoxygenated in the capillaries, it easily binds with H+ , which are released when CO2 enters the capillaries.
  • 79. 31/01/2025 79 REGULATION OF ACID-BASE BALANCE BY RESPIRATORY MECHANISM: CO2 + H2O → H2CO3 → H+ + HCO3 – • Entire reaction is reversed in lungs when CO2 diffuses from blood into the alveoli of lungs • When metabolic activities increase, more amount of CO2 is produced in the tissues and the concentration of H+ increases as seen above • Increased H+ concentration increases the pulmonary ventilation (hyperventilation) by acting through the chemoreceptors • Due to hyperventilation, the excess of CO2 is removed from the body
  • 80. 31/01/2025 80 • Kidney maintains the acid- base balance of the body by the secreting H+ and retaining HCO3 – . REGULATION OF ACID-BASE BALANCE BY RENAL MECHANISM
  • 81. 31/01/2025 81 DISTURBANCES OF ACID-BASE STATUS
  • 82. 31/01/2025 82 DISTURBANCES OF ACID-BASE STATUS – ACIDOSIS • Condition of reduced pH (increase in H+ concentration) below normal range. • Acidosis is produced by: 1. Increase in partial pressure of CO2 in the body fluids particularly in arterial blood 2. Decrease in HCO3 – concentration.
  • 83. 31/01/2025 83 DISTURBANCES OF ACID-BASE STATUS – ALKALOSIS • Condition of increased pH (decrease in H+ concentration) above the normal range. • Alkalosis is produced by: 1. Decrease in partial pressure of CO2 in the arterial blood 2. Increase in HCO3 – concentration.
  • 84. 31/01/2025 84 DISTURBANCES OF ACID-BASE STATUS – ALKALOSIS • Arterial blood is controlled by lungs, thus acid-base disturbances due to change in arterial pCO2 are called respiratory disturbances • Disturbances in acid-base status due to change in HCO3 – concentration are generally called the metabolic disturbances • Thus the acid-base disturbances are: – Respiratory acidosis – Respiratory alkalosis – Metabolic acidosis – Metabolic alkalosis
  • 85. 31/01/2025 85 RESPIRATORY ACIDOSIS • Acidosis that is caused by alveolar hypoventilation. • During hypoventilation the lungs fail to expel CO2. • CO2 accumulates in blood where it reacts with water to form carbonic acid, which is called respiratory acid. • Carbonic acid dissociates into H+ and HCO3 – . • The increased H+ concentration in blood leads to decrease in pH and acidosis. • Normal partial pressure of CO2 in arterial blood is about 40 mm Hg. When it increases above 60 mm Hg acidosis occurs.
  • 86. 31/01/2025 86 RESPIRATORY ALKALOSIS • Alkalosis that is caused by alveolar hyperventilation. • Hyperventilation causes excess loss of CO2 from the body. • Loss of CO2 leads to decreased formation of carbonic acid and decreased release of H+ . • Decreased H+ concentration increases the pH leading to respiratory alkalosis. • When the partial pressure of CO2 in arterial blood decreases below 20 mm Hg, alkalosis occurs
  • 87. 31/01/2025 87 METABOLIC ACIDOSIS • Acid-base imbalance characterized by excess accumulation of organic acids in the body, which is caused by abnormal metabolic processes. • Organic acids such as lactic acid, ketoacids and uric acid are formed by normal metabolism • The quantity of these acids increases due to abnormality in the metabolism
  • 88. 31/01/2025 88 METABOLIC ALKALOSIS: • Metabolic alkalosis is the acid-base imbalance caused by loss of excess H+ resulting in increased HCO3 – concentration. • Some of the endocrine disorders, renal tubular disorders, etc. cause metabolic disorders leading to loss of H+ . • It increases HCO3 – and pH in the body leading to metabolic alkalosis