Chapter 1: Biochemical
Perspective on Medicine
Section 1: Chemical Basis
of Life
HISTORICAL BACKGROUND OF BIOCHEMISTRY
MILESTONES IN THE HISTORY OF BIOCHEMISTRY
BIOMOLECULES
More than 99% of the human body is composed of six elements, i.e., oxygen,
carbon, hydrogen, nitrogen, calcium and phosphorus. The human body is
composed of about 60% water, 15% proteins, 15% lipids, 2% carbohydrates and
8% minerals.
Molecular structures in organisms are built from 30 small precursors, sometimes
called the alphabets of biochemistry. These include 20 amino acids, two purines,
three pyrimidines, sugars (glucose and ribose), palmitate, glycerol and choline.
Major complex biomolecules are proteins, polysaccharides, lipids and nucleic
acids. The macromolecules associate with each other by noncovalent forces to
form supramolecular systems, e.g., ribosomes, lipoproteins.
STUDY OF METABOLIC PROCESSES
Our food contains carbohydrates, fats and proteins as principal ingredients.
These macromolecules are to be first broken down to small units; carbohydrates
to monosaccharides and proteins to amino acids.
This process is taking place in the gastrointestinal tract and is called digestion or
primary metabolism.
After absorption, the small molecules are further broken down and oxidized to
carbon dioxide. In this process, NADH and FADH2 are generated.
This is named as secondary or intermediary metabolism.
Finally, these reducing equivalents enter the electron transport chain in the
mitochondria, where they are oxidized to water; in this process, energy is trapped
as ATP. This is termed tertiary metabolism.
BACTERIAL AND MAMMALIAN CELLS
STABILIZING FORCES
IN MOLECULES
Covalent Bonds: Molecules
are formed by sharing of
electrons between atoms
Ionic Bonds or
Electrostatic Bonds: Ionic
bonds result from the
electrostatic attraction
between two ionized
groups of opposite charges
STABILIZING FORCES IN MOLECULES…
These are formed by sharing one hydrogen between two electron donors.
Hydrogen bonds result from electrostatic attraction between an electro-negative
atom and a hydrogen atom that is bonded covalently to a second electronegative
atom.
In biological systems, both donors and acceptors are usually nitrogen or oxygen
atoms, especially the atoms in amino (NH2) and hydroxyl (OH) groups
With regard to protein chemistry, hydrogen releasing groups are —NH
(imidazole, indole, peptide); -OH (serine, threonine) and —NH2 (arginine lysine)
HYDROPHOBIC INTERACTIONS
Nonpolar groups tend to associate
with each other in an aqueous
environment; referred to as
hydrophobic interaction.
These are formed by interactions
between nonpolar hydrophobic side
chains by elimination of water
molecules.
The force that causes hydrophobic
molecules or nonpolar portions of
molecules to aggregate together
rather than dissolve in water is called
the ‘hydrophobic bond’.
VAN DER WAALS FORCES
These are very weak forces of attraction between all atoms, due to oscillating
dipoles, described by the Dutch physicist Johannes van der Waals, who got Nobel
Prize in 1910.
Van der Waals forces are short range attractive forces between chemical groups
in contact.
These interactions occur in all types of molecules, both polar and nonpolar.
The energy of the van der Waals interaction is about 1 kcal/mol and is unaffected
by changes in pH.
This force will drastically reduce when the distance between atoms is increased.
WATER: THE UNIVERSAL SOLVENT
Water constitutes about 70 to 80
percent of the weight of most cells.
The hydrogen atom in one water
molecule is attracted to a pair of
electrons in the outer shell of an
oxygen atom in an adjacent molecule.
The structure of liquid water contains
hydrogen bonded networks
The crystal structure of ice contains a
tetrahedral arrangement of water
molecules. Four other molecules
bound by hydrogen bonds surround
each oxygen atom.
PRINCIPLES OF THERMODYNAMICS
Thermodynamics is concerned with the flow of heat, and it deals with the
relationship between heat and work.
Bioenergetics, or biochemical thermodynamics, is the study of the energy
changes accompanying biochemical reactions.
First Law of Thermodynamics
The total energy of a system, including its surroundings, remains constant.
Or ΔE = Q – W, where Q is the heat absorbed by the system and W is the work
done. This is also called the law of conservation of energy. If heat is transformed
into work, there is proportionality between the work obtained and the heat
dissipated. A system is an object or a quantity of matter, chosen for observation.
All other parts of the universe, outside the boundary of the system, are called the
surroundings.
SECOND LAW OF THERMODYNAMICS
The total entropy of a system must increase if a process is to occur
spontaneously. A reaction occurs spontaneously if ΔE is negative, or if the
entropy of the system increases.
Entropy (S) is a measure of the degree of randomness or disorder of a system.
Entropy becomes maximum in a system as it approaches true equilibrium.
Enthalpy is the heat content of a system and entropy is that fraction of enthalpy
which is not available to do useful work.
GIBBS FREE ENERGY CONCEPT
Gibbs put forward a model in which the term “free energy” is used to get an
equation combining the first and second laws of thermodynamics.
Thus, ΔG = ΔH – TΔS, where ΔG is the change in free energy, ΔH is the change in
enthalpy or heat content of the system and ΔS is the change in entropy.
The term free energy denotes a portion of the total energy change in a system
that is available for doing work.
For most biochemical reactions, it is seen that ΔH is nearly equal to ΔE. So, ΔG =
ΔE – TΔS.
Hence, ΔG or free energy of a system depends on the change in internal energy
and the change in entropy of a system.
STANDARD FREE ENERGY CHANGE
It is the free energy change under standard conditions. It is designated as ΔG0.
The standard conditions are defined for biochemical reactions at a pH of 7 and 1
M concentration and represented by a priming sign ΔG0’.
It is directly related to the equilibrium constant. Actual free energy changes
depend on the reactant and product.
Most of the reversible metabolic reactions are near equilibrium reactions and
therefore their ΔG is nearly zero.
The net rate of near equilibrium reaction is effectively regulated by the relative
concentration of substrates and products.
THREE TYPES OF REACTIONS
1. A reaction can occur spontaneously when ΔG0 is negative. Then the reaction is
exergonic. If ΔG0 is of great magnitude, the reaction goes to completion and is
essentially irreversible.
2. 2. When ΔG0 is zero, the system is at equilibrium.
3. For reactions where the ΔG0 is positive, an input of energy is required to drive the
reaction. The reaction is termed as endergonic and those with a negative ΔG0 as exergonic.
Similarly, a reaction may be exothermic (ΔH is negative), isothermic (ΔH is zero) or
endothermic (ΔH is positive). The energetically unfavorable reaction may be driven forward
by coupling it with a favorable reaction.
Glucose + Pi → Glucose-6-phosphate (reaction 1)
ATP + H2O → ADP + Pi (reaction 2)
Glucose + ATP → Glucose-6-phosphate + ADP (reaction 3)
DONNAN MEMBRANE EQUILIBRIUM
The products of diffusible electrolytes
in both compartments are equal.
The electrical neutrality of each
compartment is maintained.
The total number of a particular type
of ions before and after the
equilibrium is the same.
As a result, when there is a
nondiffusible anion on one side of a
membrane, the diffusible cations are
more, and diffusible anions are less,
on that side.
CLINICAL APPLICATIONS OF THE DONNAN
EQUATION
The total concentration of solutes in plasma will be more than that of a solution
of the same ionic strength containing only diffusible ions; this provides the net
osmotic gradient (see under Albumin, in Chapter 19).
The lower pH values within tissue cells than in the surrounding fluids are partly
due to the concentrations of negative protein ions within the cells being higher
than in surrounding fluids.
The pH within red cells is lower than that of the surrounding plasma due to the
very high concentration of negative non-diffusible hemoglobin ions. This causes
an unequal distribution of H+ ions with a higher concentration within the cell.
The chloride shift in erythrocytes (Chapter 16) and the higher concentration of
chloride in CSF (Chapter 21) are also due to the Donnan effect.
OSMOSIS
Osmosis is an important property of
particles in solution.
Osmosis is the spontaneous net movement
of solvent molecules through a
semipermeable membrane into a region of
higher solute concentration, in the
direction that tends to equalize the solute
concentrations on the two sides.
Osmosis is the movement of a solvent
across a semipermeable membrane toward
a higher concentration of solute.
Osmosis is a passive movement. In
biological systems, the solvent is water. The
word “osmosis” descends from the Greek
word, “osmos” which means “to push”
OSMOTIC PRESSURE
Osmotic pressure is defined as the external pressure required to be applied so
that there is no net movement of the solvent across the membrane.
Osmotic pressure is a colligative property, meaning that the osmotic pressure
depends on the molar concentration of the solute but not on its identity.
The pressure required to prevent the passage of water through a selectively
permeable membrane is the measurement of osmotic pressure.
TONICITY
Living cells have a selectively permeable membrane that is very permeable to
water and some low molecular weight solutes, but much less permeable to other
substances.
This leads to the inflow of some solute molecules along with the solvent while
others are retained.
Under these conditions, the solution exhibits only the fraction of its total osmotic
pressure, due to the solutes, which are retained.
This fraction of the total osmotic pressure of a solution is termed its tonicity.
OSMOTIC GRADIENT
The osmotic gradient is the difference in concentration between two solutions on
either side of a semipermeable membrane.
It is a measure of the difference in the concentration of a specific particle
dissolved in a solution.
Water will diffuse toward the hypertonic solution (the solution with the higher
concentration of solute).
Osmolarity means osmotic pressure exerted by the number of moles per liter of
solution.
Osmolality is the osmotic pressure exerted by the number of moles per kg of
solvent. Crystalloids and water can easily diffuse across membranes, but an
osmotic gradient is provided by the non-diffusible colloidal (protein) particles
REVERSE OSMOSIS
Suppose a solution is separated from pure solvent by a semipermeable
membrane.
If the pressure applied to the solution is more than the osmotic pressure, the
solvent will start flowing from the solution towards the pure solvent.
This phenomenon is known as reverse osmosis.
DIALYSIS
The process of separating crystalloids from colloids by means of diffusion of
crystalloids through a membrane is called dialysis and the apparatus used for
separation is called a dialyzer.
This method is based on the fact that the pores of the membrane are very small
and allow the free passage of only ions of the solution.
The colloidal particles are too big to pass through these pores and hence they are
retained inside the bag.
EQUIVALENT WEIGHT
Equivalent weight is the mass of a substance in grams that combines with or is
chemically equivalent to eight grams of oxygen or one gram of hydrogen.
The equivalent weight is calculated as the molecular weight divided by the
valency.
MOLECULAR WEIGHT
Molecular weight ([Link]) is the average mass of a molecule of a compound compared
to 1⁄12 the mass of 12C (carbon-12).
(By definition, the weight of isotope of 12C is equal to 12) Molecular mass or molecular
weight is the mass of a molecule. It is calculated as the sum of the atomic weights of the
constituent atoms.
A mole is the unit of amount of pure substance in the International System of Units (SI
units) that contains the same number of atoms as there are atoms in exactly 12 grams of
the isotope carbon 12 (12C). The mole is abbreviated as “mol”.
Molarity: The concentration of a solution is commonly expressed by its molarity, which is
defined as the number of moles of the dissolved substance per liter of solution.
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