1. The importance of biochemistry for
medicine.
Functional groups and types of
chemical bonds specific for
biomolecules.
Amino acids – biomedical role,
structure, classification and
properties
2. The importance of biochemistry
for medicine.
Biochemistry and medicine enjoy a
mutually cooperative relationship.
Biochemical studies have
illuminated many aspects of health
and disease, and the study of
various aspects of health and
disease has opened up new areas of
biochemistry.
3. The importance of biochemistry
for medicine.
Biochemistry makes significant
contributions to the fields of cell
biology, physiology, immunology,
microbiology, pharmacology, and
toxicology, as well as the fields of
inflammation, cell injury, and cancer.
These close relationships emphasize
that life depends on biochemical
reactions and processes.
4. The importance of biochemistry
for medicine.
In physiology, the study of body
function, biochemistry has broadened
our understanding of how
biochemical changes relate to
physiological alteration in the body.
It helps us understand the chemical
aspects of biological processes such
as digestion, hormonal action, and
muscle contraction-relaxation.
7. Functional groups
A functional group is defined as an
atom or a group of atoms that
effectively determines the chemical
properties of an organic compound.
24. Chemical Bond
A single covalent bond, or single bond, is the sharing
of one pair of valence electrons
•A double covalent bond, or double bond, is the
sharing of two pairs of valence electrons
•Covalent bonds can form between atoms of the same
element or atoms of different elements
•A molecule is two or more covalently bonded atoms
25. Chemical Bond
A bond results from the attraction of nuclei for
electrons
All atoms trying to achieve a stable octet
IN OTHER WORDS
the p+ in one nucleus are attracted to the e- of another
atom
Electronegativity
26. 26
The ability of an atom in a molecule to attract
shared electrons to itself.
For a molecule HX, the relative electronegativities
of the H and X atoms are determined by
comparing the measured H–X bond energy with
the “expected” H–X bond energy.
27. Electronegativity
On the periodic table, electronegativity generally
increases across a period and decreases down a
group.
The range of electronegativity values is from 4.0
for fluorine (the most electronegative) to 0.7 for
cesium and francium (the least electronegative).
33. H F F
H
Polar covalent bond or polar bond is a covalent
bond with greater electron density around one of the
two atoms (electrons are shared unequally)
electron rich
region
electron poor
region e- rich
e- poor
d+ d-
9.5
36. Ionic Bond
Between atoms of metals and nonmetals with very
different electronegativity
Bond formed by transfer of electrons
Produce charged ions all states. Conductors and have
high melting point.
Examples; NaCl, CaCl2, K2O
37.
38. Ionic bond
Liquid or dissolved ionic substance possesses
electrical conductivity
Ionic substances are eazy disosiate to form ions
Ionic bond energy is less than the energy
of the covalent bond
39. IONic bonding
Always formed between metals and non-metals
[METALS ]
+ [NON-METALS ]
-
Lost e-
Gained e-
41. Coordinate covalent bonds
(dative)
A covalent bond that occurs between two atoms in
which both electrons shared in the bond come from
the same atom.
Both electrons from the nitrogen are shared with the
upper hydrogen
Ammonium has 3 polar covalent bonds and 1
coordinate (dative) covalent bond.
43. Attractions between
molecules
van der Waals forces
Weak attractive
forces between non-
polar molecules
Hydrogen “bonding”
Strong attraction
between special polar
molecules
Intermolecular attractions
44. van der Waals
Non-polar molecules can exist in liquid and solid
phases
because van der Waals forces keep the molecules
attracted to each other
Exist between CO2, CH4, CCl4, CF4, diatomics and
monoatomics
45. van der Waals
Van der Waals bonds meet in nonpolar molecules.
The existence of these connections is explained by
the fact that in nonpolar molecules exist
permanent movements of electrons, which can
give rise to an electric dipole that induced
polarization the surrounding molecules.
This polarization spreads throughout the mass of
hole substances determining the occurrence of
non-permanent dipole that produse attraction
between molecules
46. Hydrogen Bond
when a hydrogen atom, covalently bonded to one
electronegative atom, is attracted to another
electronegative atom
•Example: water (H2O)
•Weak, but many together are strong
47. Hydrogen “Bonding”
Strong polar attraction
Like magnets
Occurs ONLY between
H of one molecule and
N, O, F of another
H “bond”
48. H is shared between
2 atoms of OXYGEN or
2 atoms of NITROGEN or
2 atoms of FLUORINE
Of
2
different
molecules
49. Order of Relative Bond Strength
Covalent >ionic> hydrogen> van der waals
In biological systems, often many weak bonds
collectively are strong and help stabilize structures.
Example: DNA double helix:
held together through H-bonds
51. Strands are complementary
.
Pyrimidine and purine bases are located
inside of the double helix in such a way that
opposite a pyrimidine base of one chain is located
a purine base of another chains and between them
hydrogen bonds appear. These pairs are called
complementary bases (T-A and C-G). Between
adenine (A) and thymine (T) two hydrogen bonds
appear, and between guanine (G) and cytosine –
three:
Hydrogen bonds between complementary bases is one of the
interaction forces that stabilize the double helix.
53. Amino acids (AA) are particularly
important for the human body:
• are the basic structural elements of
proteins;
• are precursors of the hormones,
purine and pyrimidine nitrogenous
bases, porphyrins, vitamins and
biogenic amines.
54. -Amino acids are heterofunctional
compounds containing carboxyl and amine
groups linked to the same -carbon atom.
Amino acid radical (R) - is also joined to the
-carbon atom.
The general formula of -amino acids is:
55. Stereoisomery of amino acids
All representatives of -amino acids (except glycine)
contain a chiral α-carbon atom and form stereoisomers
(enantiomers) - L and D.
In the protein structure in living organisms only
L-α-amino acids are used.
56. Under physiological pH, in aqueous solution -amino acids exist
in the form of bipolar ions (zwitterions):
• the amino group is protonated (-NH3+ ) and have basic
properties - is a proton acceptor;
• carboxyl group is dissociated (deprotonated) (-COO-) and
has acidic properties - is a proton donor;
Acid-base properties of -amino acids
Thus, the amino acids have amphoteric properties:
both - basic and acidic.
57. Classification of amino acids
• In dependence of radical (R) structure (there are
aliphatic (acyclic) – aromatic (cyclic); thio-; hydroxi;)
• In dependence of physical-chemical properties
(acidic – dicarboxo monoaminic AA, basic – diamino
monocarboxilic AA and neutral monoamino
monocarboxilic AA)
• In dependence of biological function: essential
AA- which not synthesize in the body and
nonessential AA, which synthesize in our body.
59. Common amino acids can be placed in five
basic groups depending on their R
substituents:
• Nonpolar, aliphatic (7)
• Aromatic (3)
• Polar, uncharged (5)
• Positively charged (3)
• Negatively charged (2)
60. Acidic and basic AA are polar (hydrophylic)
Neutral AA can be polar and non polar. Amino acids
with a non-polar (hydrophobic) side chain:
glycine, alanine, valine, leucine, isoleucine,
proline, phenylalanine, tryptophan and
methionine. All of them are less soluble in water
than the polar amino acids;
Amino acids with a polar (hydrophilic) neutral
side chain (at pH = 6): serine, threonine, cysteine,
tyrosine, asparagine, glutamine. These amino acids
are more soluble in water than the non-polar
amino acids, due to -OH, -NH2 , amide and -SH
functional groups that can interact with water;
66. Basic amino acids
Basic amino acidsContain two or more NH2 groups or
nitrogen atoms that
act as base i.e. can bind proton.
At physiological pH, basic amino acids will be positively
charged.
Arginine: contains guanido group
Histidine: is an example on basic heterocyclic amino
acids
69. Acidic Amino acids
Acidic Amino acids: at physiological pH will carry
negative charge.
e.g. Aspartic acid (aspartate) and Glutamic acid
(glutamate)
Aspargine and Glutamine: They are amide forms of
aspartate and glutamate in which side chain COOH groups
are amidated.
They are classified as neutral amino acids.
72. Classification of amino acids according to the
physico-chemical properties of the side chain
1. Amino acids with a non-polar (hydrophobic) side chain: glycine,
alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan and
methionine. All of them are less soluble in water than the polar amino acids;
2. Amino acids with a polar (hydrophilic) neutral side chain (at pH = 6):
serine, threonine, cysteine, tyrosine, asparagine, glutamine. These amino
acids are more soluble in water than the non-polar amino acids, due to -OH,
-NH2 , amide and -SH functional groups that can interact with water;
3. Amino acids with a polar (hydrophilic) negatively charged side chain
(at pH = 6): aspartic acid and glutamic acid;
4. Amino acids with a polar (hydrophilic) positively charged side chain
(at pH = 6): lysine, arginine, histidine.
73. Classification by chemical structure:
by the chemical structure of the side chain:
Examples:
By the number of –COOH and –NH2 groups:
Examples:
74. by the presence of other functional groups in the chain –
Examples:
Imino acid -
Classification by chemical structure:
76. III- Nutritional classification:
1- Essential amino acids: These amino acids can’t be formed
in the body and so, it is essential to be taken in diet. Their
deficiency affects growth, health and protein synthesis.
2- Semiessential amino acids: These are formed in the body
but not in sufficient amount for body requirements especially
in children.
Summary of essential and semiessential amino acids:
Villa HM = Ten Thousands Pound
V= valine i= isoleucine l= lysine l= leucine
A = arginine* H= histidine* M= methionine
T= tryptophan Th= threonine P= phenyl alanine
*= arginine and histidine are semiessential
3- Non essential amino acids: These are the rest of amino
acids that are formed in the body in amount enough for adults
and children. They are the remaining 10 amino acids.
77. Classification of amino acids by the
presence in protein and genetic encoding
Amino acids
Proteinogenic –
enter in the
composition of
proteins
Genetically encoded -
the 20 amino acids,
possessing codons in the
genetic code
Non-encoded (post-
translationally modified ) – don’t
have codons, are synthesized from
the proteinogenic
Non-proteinogenic
– don’t enter in the
composition of
proteins
80. IV- Metabolic classification: according to metabolic or
degradation products of amino acids they may be:
1- Ketogenic amino acids: which give ketone bodies . Lysine
and Leucine are the only pure ketogenic amino acids.
2- Mixed ketogenic and glucogenic amino acids: which give
both ketonbodies and glucose.These are: isoleucine, phenyl
alanine, tyrosine and tryptophan.
3- Glucogenic amino acids: Which give glucose. They include
the rest of amino acids. These amino acids by catabolism yields
products that enter in glycogen and glucose formation.
81. Amphoteric properties of amino acids: that is they have both basic
and acidic groups and so can act as base or acid.
Neutral amino acids (monobasic, monocarboxylic) exist in aqueous
solution as “ Zwitter ion” i.e. contain both positive and negative
charge. Zwitter ion is electrically neutral and can’t migrate into
electric field.
Isoelectric point (IEP) = is the pH at which the zwitter ion is
formed. e.g IEP of alanine is 6
Chemical properties of amino acids:
1- Reactions due to COOH group:
- Salt formation with alkalis, ester formation with alcohols, amide
formation with amines and decarboxylation
- 2- Reactions due toNH2 group: deamination and reaction with
ninhydrin reagent.
- Ninhydrin reagent reacts with amino group of amino acid yielding
blue colored product. The intensity of blue color indicates quantity of
amino acids present
82. Amphoteric properties of amino acids: that is they have both basic
and acidic groups and so can act as base or acid.
Neutral amino acids (monobasic, monocarboxylic) exist in aqueous
solution as “ Zwitter ion” i.e. contain both positive and negative
charge. Zwitter ion is electrically neutral and can’t migrate into
electric field.
Isoelectric point (IEP) = is the pH at which the zwitter ion is
formed. e.g IEP of alanine is 6
Chemical properties of amino acids:
1- Reactions due to COOH group:
- Salt formation with alkalis, ester formation with alcohols, amide
formation with amines and decarboxylation
- 2- Reactions due toNH2 group: deamination and reaction with
ninhydrin reagent.
- Ninhydrin reagent reacts with amino group of amino acid yielding
blue colored product. The intensity of blue color indicates quantity of
amino acids present.
83. Acid-base properties of -amino acids
In an acidic solution (pH <7) the amino acid is protonated and exist as a
cation; in an alkaline solution (pH> 7), the amino acid is deprotonated, and
exists as an anion. Thus, at some intermediate pH, the amino acid must be
balanced exactly between the anionic and cationic forms and exists as a
neutral bipolar ion (zwitterion). This pH is called isoelectric point (Pi).
In isoelectric point the zwitterion has a summary charge = 0
and is in an isoelectric state.
84. Acid-base properties of -amino acids
Amino acids differ by side chain (radical),
which gives them specific properties. The
radical can have hydrophobic or
hydrophilic properties. Hydrophilic radicals
may be neutral, acidic or basic, depending
on the functional groups.
In case the side chain of an amino acid is hydrophobic or hydrophilic neutral
- it will not affect the total electric charge of the amino acid and its acidic or
basic properties.
The hydrophilic acidic side chain in neutral medium have a negative charge
and the amino acid is an anion. The hydrophilic basic side chain in neutral
medium have a positive charge and the amino acid is a cation. In order to have
such amino acids in the isoelectric state - it is necessary to change the pH of
the medium.
85. Thus, the isoelectric point of the amino acids will vary from low values (pI <7) for
acidic amino acids (pI=2.87 for aspartic acid) to high values (pI> 7) for basic amino
acids (pI=10.8 for arginine). Neutral amino acids don’t have the isoelectric point at
a neutral pH, as it would be expected, but in week acidic medium (pI = 5-6).
86. 86
pI =
pKax + pKay
2
pI =
pKa2 + pKa3
2
pI = 9.7
pI =
pKa1 + pKa3
2
pI = 2.7
pI =
pKa1 + pKa2
2
pI = 6.0
87. Peptides and Proteins
20 amino acids are commonly found in protein.
These 20 amino acids are linked together through “peptide
bond forming peptides and proteins (what’s the difference?).
- The chains containing less than 50 amino acids are called
“peptides”, while those containing greater than 50 amino acids
are called “proteins”.
Peptide bond formation:
α-carboxyl group of one amino acid (with side chain
R1) forms a covalent peptide bond with α-amino group of
another amino acid ( with the side chain R2) by removal of
a molecule of water. The result is : Dipeptide ( i.e. Two
amino acids linked by one peptide bond). By the same way,
the dipeptide can then forms a second peptide bond with a
third amino acid (with side chain R3) to give Tripeptide.
Repetition of this process generates a polypeptide or
protein of specific amino acid sequence.
88.
89. The peptide bond is formed between the α-carboxylic group of one
amino acid and the α-amino group of the following amino acid :
90.
91. Each polypeptide chain starts on the left side by free
amino group of the first amino acid enter in chain
formation . It is termed (N- terminus).
- Each polypeptide chain ends on the right side by free
COOH group of the last amino acid and termed (C-
terminus).
92. • The classical peptide bond is a strong covalent bond and has the properties of
partially double bond.
• The peptide bond is planar - all the atoms of the peptide group are in the same
plane.
The properties of peptide bond:
93. • The classical peptide bond has trans- conformation.
• Peptide bond has two resonance forms - keto and
enol :
The properties of peptide bond:
94. • Each classical peptide bond is capable of forming 2 hydrogen
bonds with other polar atoms.
• Proline forms an atypical peptide bond :
The properties of peptide bond:
95. The end of the peptide chain with the -NH2 group is known as
the N-terminal, and is considered the beginning of the chain;
and the end with the -COOH group is the C-terminal.
The conformation of a peptide chain has a form of a zig-zag :
The "R" groups come from the 20 amino acids which occur in
proteins. The peptide chain is known as the backbone, and the
"R" groups are known as side chains.
"R" – side chains of the amino acids - they are maximal distant in
space from each other.
Each protein has a specific sequence of amino acids which are
assembled under the direction and control of nucleic acids.
96. The products of the polycondensation of -amino acids linked
by peptide bonds are called peptides:
A peptide containing two amino acids is called a dipeptide;
containing three amino acids – a tripeptide; and so on.
A chain containing up to 50 amino acids, is called
oligopeptide; containing 50-100 amino acids -
polypeptide;
If the number is greater than 100 amino acids, the
polypeptide is called protein.
97. Nomenclature of peptides
All amino acids in the polypeptide chain situated on the left to the C-terminus
have –yl terminus and the C-terminal keeps its trivial name. For example:
tripeptide Gly-Ala-…-Ser will be called glycyl-alanyl-…-serine.
98. The sequence of amino acids in a protein is called
primary structure of protein
99. Determination of the primary structure of proteins
It has two main steps:
1. Determination of the amino acid composition of the peptide or protein;
2. Determination of the sequence of amino acids into polypeptide chain.
•The amino acid composition is determined by the analysis of protein
hydrolysates. The total hydrolysis may be carried out by boiling the
protein in a solution of 6M hydrochloric acid or by enzymes. All the peptide
bonds are cleaved. For example:
•The determination of each amino acid in the hydrolyzate is carried out by
chromatography. Currently such an analysis is performed automatically
using special devices called amino acid analyzers.
100. The sequence of amino acid is determined in several
stages:
1. - selective partial hydrolysis of the polypeptide in shorter
peptides (via several enzymatic or chemical methods);
2 - sequential identification of -amino acids from the N- or
C-terminal end for each peptide; as a rule the Edman
method is applied;
3. – determination of the peptide order in polypeptide by
overlapping and determination of the coincidence segments
("fingerprints“ method or "peptide mapping method“
Determination of the primary structure of proteins
101. Edman Method
- consists in the interaction of N-terminal amino acid with phenylisothiocyanate in
weak basic medium. At a subsequent treatment with a weak acid without heating a
cleavage of the N-terminal amino acid as a phenylthiohydantoin derivative
occurs. This compound can be further identified by chromatographic method. This
procedure is repeated several times until complete cleavage of the peptide
fragment takes place:
Edman method has been shown to be useful for reproduction in an automatic device
called sequencer. It can performe 40-50 cleavage steps.
102. Examples on Peptides:
1- Dipeptide ( tow amino acids joined by one peptide bond):
Example: Aspartame which acts as sweetening agent being used in
replacement of cane sugar. It is composed of aspartic acid and phenyl
alanine.
2- Tripeptides ( 3 amino acids linked by two peptide bonds).
Example: GSH which is formed from 3 amino acids: glutamic acid, cysteine
and glycine. It helps in absorption of amino acids, protects against
hemolysis of RBC by breaking H2O2 which causes cell damage.
3- octapeptides: (8 amino acids)
Examples: Two hormones; oxytocine and vasopressin
(ADH).
4- polypeptides: 10- 50 amino acids: e.g. Insulin hormone
105. Reactions of biological importance
1. Transamination of -amino acids:
- is the transferring of the amino group from the donor
amino acid to an -keto acid – acceptor of the amino
group. In this reaction the -amino acid is converted
to a keto acid, and the keto acid is converted to an
amino acid:
106. For example, the transamination reaction
between glutamic acid and oxaloacetate: it
produces a new amino acid - aspartic acid and a
new keto acid - α-ketoglutarate:
107. 2. Decarboxylation of -amino acids:
- in the decarboxylation reaction the -amino acids lose the
-carboxylic group and are converted into biogenic amines
For example:
a) decarboxylation of glutamic acid and gamma-aminobutyric
acid (GABA) formation:
Reactions of biological importance
108. b) Decarboxylation of histidine and histamine formation:
C) Decarboxylation of 5-hydroxy tryptophan and serotonine formation:
109. 3. Hydroxylation of -amino acids:
4. Carboxilation of amino acids:
Reactions of biological importance
