Books to consult
(1) Lehninger Principles of Biochemistry
by D L Nelson& M M Cox Edition 6
(2) Essentials Of Medical Biochemistry
By Mushtaq Ahmad Volume 1
Fundamentals of Biochemistry
for Medical students
By;
M. Sheraz Yasin
Lecturer,
Institute of Biochemistry and Biotechnology,
University of Veterinary and Animal Sciences, Lahore.
Introduction
•What is the Biochemistry?
•History and development
•How to study Biochemistry?
1. Biochemistry
•Definition: The chemistry of life
–The science concerned with the chemical basis of
life.
–The science concerned with the various molecules
that occur in living cells and organisms and with their
chemical reaction.
–Anything more than a superficial comprehension of
life – in all its diverse manifestation - demands a
knowledge of biochemistry.
•Biochemistry is the branch of science that
explores the chemical processes within and
related to living organisms. It is a laboratory
based science that brings together biology
and chemistry. By using chemical
knowledge and techniques, biochemists can
understand and solve biological problems.
2
Biochemical reaction
•A biochemical reaction is the
transformation of one molecule to a
different molecule inside a cell.
Biochemical reactions are mediated by
enzymes, which are biological catalysts that
can alter the rate and specificity of chemical
reactions.
Biochemistry
•Significance: be essential to all life
sciences as the common knowledge
–Genetics; Cell biology; Molecular biology
–Physiology and Immunology
–Pharmacology and Pharmacy.Nutrition
–Toxicology; Pathology; Microbiology
–Zoology and Botany
Medical biochemistry
•Medical biochemistry is a field that studies
different types of molecules in hopes of
bettering technology and medicine. In order
to work in the medical biochemistry
environment
Biochemistry
–Medical students who acquire a sound knowledge of
biochemistry will be in a strong position to deal with
two central concerns of the health sciences:
(1) the understanding and maintenance of
health
(2) the understanding and effective
treatment of disease
•Causes of cancers
•Molecular lesions causing various genetic diseases
•Rational design of new drugs
History and development of Biochemistry
1903, Neuberg (German):
“Biochemistry”
“Chemistry of Life”
Two notable breakthroughs
(1) Discovery of the role of enzymes as catalysts
(2) Identification of nucleic acids as information molecules
Flow of information: from nucleic acids to proteins
DNA RNA Protein
•In 1937, Krebs for the discovery of the Citric Acid
Cycle-won the Nobel Prize in Physiology or Medicine
in 1953
•In 1953,Watson & Crick for the discovery of the
“DNA Double Helix” -won the Nobel Prize in
Physiology or Medicine in 1962
Some historic events
•In 1955,Sanger for the determination of insulin
sequence- won the Nobel Prize in Physiology or
Medicine in 1956
•In 1980, Sanger & Gilbert for Sequencing of DNA-
won the Nobel Prize in Chemistry in 1980
•In 1993, Kary B. Mullis for invention of PCR method -
won the Nobel Prize in Chemistry in 1993
What does the Biochemistry
discuss?
•structure and function of cellular
components
–proteins, carbohydrates, lipids, nucleic acids
and other biomolecules
•Metabolism and Regulation
•Gene expression and modulation
DNA RNA Protein
Polymers and Monomers
•Each of these types of molecules are
polymers that are assembled from single
units called monomers.
•Each type of macromolecule is an
assemblage of a different type of monomer.
Macromolecule
Carbohydrates
Lipids
Proteins
Nucleic acids
Monomer
Monosaccharide
Not always polymers;
Hydrocarbon chains
Amino acids
Nucleotides
• Building block
– Simple sugar
– Amino acid
– Nucleotide
– Fatty acid
• Macromolecule
– Polysaccharide
– Protein (peptide)
– RNA or DNA
– Lipid
Anabolic
Catabolic
Water And its properties
19
Structure of water
An example of bent molecular geometry that
results from tetrahedral electron pair
geometry is H2O. The water molecule is so
common that it is wise to just memorize that
water is a BENT molecule. The oxygen has 6
valence electrons and thus needs 2 more
electrons from 2 hydrogen atoms to complete
its octet. Bent angle is 104.5 degree. Polar
due more electro negative oxygen atom
Chemical feature of water
•Melting point 0 c
•Boiling point 100 c
•Heat of vaporization 2260 j/g
water is one of the most essential elements to
health and is so important that your body
actually has a specific drought management
system in place to prevent dehydration and
ensure your survival. ... The human brain is
made up of 95% water, blood is 82% and
lungs 90%.t
The body loses water through breathing,
sweating, and digestion, which is why
it's important to rehydrate by drinking fluids
and eating foods that contain water. ... Your
body uses water in all its cells, organs, and
tissues to help regulate its temperature and
maintain other bodily functions.
Hydrogen Ion Concentration &
pH
•Water is most abundant substance in the
human body making up to 60% to 70% of
the body mass.
•Water is dipolar molecule, Hydrogen bonds
exists between water molecules making it a
liquid at room temperature and give solvent
properties. Pure water is very slightly
dissociated (weak electrolyte).At25 C 1/10
million molecules in pure water is ionized.
24
Ionic Product of Water & pH
K
w = [H
+
] [OH
-
] = 10
-14
M
2
[H
+
] = [OH
-
] = 10
-7
M = 0.1 mM
[H
+
] [OH
-
]
[H
2O]
Concentration of “water in water” ([H
2O]) is 55.6 M [next slide], thus
Pure water has equal quantities of H
+
and OH
-
ions, or, put differently,
pure water has equal [H
+
] and [OH
-
].
Constant ion product!
= 1.8x10
-16
M
K
eq =
H
2O H
+
+ OH
-
Molarity Of Water
Concentration is measured in moles per liter (mol/l) or simply M.
1 l = 1,000 ml of water has a mass of 1,000 gr.
1 mole of water has a mass of 18 gr (hydrogen 1 Da, oxygen 16 Da).
Thus 1 liter of water (1,000 gr) contains 1,000 gr / 18 gr moles of water.
[H
2O] = (1,000 gr / 18 gr) M = 55.6 M.
Acidity of a solution > measured
by concentration of hydrogen
ions (H+).
pH ranges: 0 (very acidic) to 14
(very basic).
Change in just one unit of scale
= tenfold change in H+
concentration.
If concentration of H+ = OH -
… neutral.
Measurements of Acidity & Alkalinity (pH)
Images: pH scale, Edward Stevens, Wiki From the Virtual Cell Biology Classroom on ScienceProfOnline.com
pH scale is logarithmic
Image: pH & hydronium ion concentration, UBC Wiki
Change in
just one unit
of scale
= tenfold
change in H+
concentration
.
From the Virtual Cell Biology Classroom on ScienceProfOnline.com
31
• Most living cells have a very narrow
range of tolerance for pH, i.e. [H
+
].
• [H
+
] is controlled in all biological
organisms, and in virtually all biochemical
experiments.
• Each pH unit represents a factor of 10
difference in [H
+
]
• The pH effects the structure & activity of
the biological macromolecules;for example
the catalytic activity of enzymes is strongly
depentent on pH.
The pH scale goes from 0 to 14—because [H
+
][OH
-
] = 10
-14
pH profiles of enzymatic reactions
UCI Bio199 Independent Research
Pepsin
Amylase
pH of Some Biological Fluids
Body Fluids PH Body Fluids pH
Blood Plasma 7.35----7.45 Milk 6.6---6.9
Gastric juice 1.0-----3.0 Saliva 6.35----6.85
Intestinal juice 7.0-----8,2
Tears 7.4
Pancreatic juice 7.5-----8.0 Urine 4.5----8.0
8
The Conceptual Problem with pH
•Because it’s a logarithmic scale, it doesn’t make
“sense” to our brains.
•Every factor of 10 difference in [H
+
] represents 1.0
pH units, and
•Every factor of 2 difference in [H
+
] represents 0.3
pH units.
•Therefore, even numerically small differences in
pH, can have profound biological effects…
34
pH = -log [H
+
]
HCl H
+
+ Cl
-
HCl is a strong acid that completely dissociates in
water. 1 M HCl will thus yield 1 M [H
+
] and the pH will be
pH = -log [H
+
] = -log(1) = 0
NaOH is a strong base that completely dissociates in
water. 1 M NaOH will thus yield 1 M [OH
-
]. Since
[H
+
] [OH
-
] = 10
-14
M and must remain constant
[H
+
] = 10
-14
M and the pH will be
pH = -log [H
+
] = -log(10
-14
) = 14
Life is compatible only in a narrow pH range around pH 7.
Strong acids and bases
(L3) BUFFER
SOLUTION
An aqueous solution system which
tends to maintain the pH of the
solution when small amount of acid
or base is added to it .
Buffers
Buffers
•resist changes in pH from the addition of
acid or
base
•in the body absorb H
3O
+
or OH
from
foods and cellular processes to maintain
pH
•are important in the proper functioning of
cells and blood
•in blood maintain a pH close to 7.4; a
change in the pH of the blood affects the
uptake of oxygen and cellular processes
39
Buffers (continued)
When an acid or
base
is added
•to water, the pH
changes
drastically
•to a buffer
solution, the pH
does not change
very much; pH is
maintained
40
At the pK
a, [HAc] = [Ac
-
] so the system is able to absorb the addition of HO
-
or H
+
. If we add HO
-
near the pH where [Hac] = [Ac
-
] (ie pH ~= pK
a) then
HAc can release H
+
to offset the HO
-
added but the ratio of HAc to Ac
-
does
not change much. If we add H
+
then Ac
-
can absorb H
+
to form HAc.
Hence, the pH does not change much.
L4 How does a buffer work?
-
pH = pK
a + log
[Ac
-
]
[HAc]
K
a =
[H
+
] [Ac
-
]
[HAc]
Start at low pH and begin to add HO
-
.
The product of [H
+
] [HO
-
] must
remain constant, so adding HO
-
means [H
+
] must decrease and thus
pH increases. At the pK
a, [Ac
-
] and
[HAc] are equal, so adding more HO
-
does not change the ratio of [Ac
-
] to
[HAc] very much and thus the pH
does not change very much (shallow
slope of titration curve from ~1 pH
unit below pK
a to ~1 pH unit above).
Titration curves
2
Buffers are vitally important in biochemical systems
since pH needs to be controlled. Living systems must
be “buffered” to resist large variations in pH.
Phosphate
H
3PO
4 H
+
+ H
2PO
4
-
pK
a1 = 2.2
H
2PO
4
-
H
+
+ HPO
4
2-
pK
a2 = 6.86
HPO
4
2-
H
+
+ PO
4
3-
pK
a3 = 12.7
Carbonate
CO
2 + H
2O H
2CO
3
H
2CO
3 H
+
+ HCO
3
-
pK
a1 = 6.4
HCO
3
-
H
+
+ CO
3
2-
pK
a2 = 10.2
Phosphate buffering
Measuring pK
a values
NH
4
+
H
+
+ NH
3
[NH
4
+
]
[H
+
] [NH
3]
K
a =
pK
a = pH when [NH
4
+
] = [NH
3]
K
a =
[H
+
] [Ac
-
]
[HAc]
take the -log on both sides
The Henderson-Hasselbalch Equation
-log K
a = -log [H
+
] -log
[Ac
-
]
[HAc]
pH =
pK
a + log
[Ac
-
]
[HAc]
= pK
a + log
[Proton acceptor]
[Proton donor]
HAc H
+
+ Ac
-
pK
a = pH -log
[Ac
-
]
[HAc]
apply p(x) = -log(x)
and finally solve for pH…