biochemistry introduction & amino acids structure

1. Pharmaceutical
Biochemistry
(PHS 302)
Dr. Asmaa Saleh Ali

2. Textbook
• Lippincott Illustrated Reviews: Biochemistry (Lippincott Illustrated Reviews
Series) 7th Edition

3. No List ofTopics
Contact
Hours
1
Introduction to biochemistry
Amino acids and protein structure
5
2 Lipid structure & carbohydrates structure 5
3
Enzymes (types, functions, role in diagnosis of some diseases)
Vitamins and minerals (types, functions, and deficiencies)
5
4
Introduction to metabolism & Respiratory chain & oxidative phosphorylation
Carbohydrates digestion & Glycolysis
5
5
Examination #1
Krebs cycle
Gluconeogenesis
Glycogen synthesis and breakdown
5
6 Lipid digestion & metabolism 5
7 Cholesterol & lipoproteins & Ketone bodies 5
8 Nitrogen metabolism 5
9
Integration of metabolism
Metabolic abnormalities
5
10
Molecular biology (nucleic acid structure, replication, transcription & translation) &
Biotechnology
5
Final exam 2

4. # Assessment task Week Due
Percentage ofTotal
Assessment Score
1
Exam 1 (multiple choice, short answer and involving
concepts discussed in class and from assigned readings)
5 30%
2
Class Participation (quizzes, Medical report, Lecture
presentation)
1-10 30%
3
Exam 2 Cumulative final examination using the same format as
the summary exams
11 40%
Assessment

5. Introduction to
Biochemistry
Dr. Asmaa Saleh Ali

6. Objectives
By the end of this lecture, the students should understand the following:
• Definition of biochemistry
• Definition of biomolecules
• Classification of biomolecules
• Types and general functions of proteins, carbohydrates, and lipids
• Structure and function of Amino acids and Proteins

7. What is Biochemistry?
Biochemistry is a branch of medical science that describes the
structure, organization and functions of living matter in molecular
terms. It is the chemistry of life.
It is divided into 3 principal areas:
• 1. Structural chemistry
• 2. Metabolism
• 3. Chemistry of molecular genetics

8. Biomolecules
• Chemicals or molecules present
in the living organisms are
known as Biomolecules.
• Just like cells are building blocks
of tissues likewise molecules are
building blocks of cells.

11. Amino acids
• Building blocks of proteins.
• 20 commonly occurring.
• Contains amino group and carboxyl group function groups (behavioral
properties)
• R Group (side chains) determines the chemical properties of each amino
acids.
• Also determines how the protein folds and its biological function.
• Individual amino acids in protein connected by peptide bond.
• Functions as transport proteins, structural proteins, enzymes, antibodies,
cell receptors.

12. Carbohydrates
•most abundant organic molecule found in nature.
•Initially synthesized in plants from a complex series of reactions involving
photosynthesis.
•Basic unit is monosaccharides.
•Monosaccharides can form larger molecules e.g. glycogen, plant starch or
cellulose.
Functions: Provide and store energy, Supply carbon for synthesis of other
compounds, Form structural components in cells and tissues, Intercellular
communications

13. lipids
Example of lipids are
• triacylglycerol,
• streiods (cholestrol, sex hormones),
• fat soluble vitamins.
Insoluble in water
Functions
• Storage of energy in the form of fat
• Membrane structures
• Insulation (thermal blanket)
• Synthesis of hormones

15. Amino acids and protein
structures
Dr. Asmaa Saleh Ali

16. Definition:
Amino acids are building blocks of protein
(Proteins are polymers of amino acids linked by peptide bond)
Importance of amino acids:
 building blocks of proteins
 Precursors for non protein specialized products (histamine, GABA)
 energy source

17. 1- enzymes
2- hormones
3- structural
4- transport
5- immunoglobulins
6- clotting factors
7- complements
8- buffers
Importance of proteins:

19. Amino Acid Structure
• More than 300 amino acids have been
discover
• In mammals, 20 amino acids make up every
protein
• Each amino acid contains a carboxyl group
• Each amino acid contains a primary amino
group except for proline which has a
secondary amino group
• A side chain (R) is present in every amino
acid and is connected to the α carbon

20. Amino Acid Structure
• Each amino acid contains a primary amino group
except for proline which has a secondary amino group

21. Amino Acid Structure
• The human body function at a physiological pH of
7.4
• At this physiological pH, both the carboxyl group
and the amino group dissociate
• The carboxyl group dissociate to give the
negatively charged carboxylate ion ( COO–)
• While the amino part is protonated to form a
positively charged amine ( NH3+)
• The role of any amino acid is decided according
to the nature of the side chain (R)

22. Amino Acid Classification
• Each amino acid is classified according to the chemical properties of the
side chain
• As a result, the 20 amino acids are divided into polar and non-polar
amino acids
• Polar amino acid is further classified at physiological pH to
• 1- No charge polar amino acids
• 2- Positively charged amino acids
• 3- Negatively charged amino acids

23. Non-Polar Amino Acids
• They has hydrophobic characteristic
• They have no charge on the side chain
• They have low water solubility
• They create the core of most globular proteins

26. Polar Amino Acids
Uncharged
• Serine, threonine, and tyrosine each contain a polar hydroxyl group
that can participate in hydrogen bond formation.
• The side chains of asparagine and glutamine each contain a
carbonyl group and an amide group, both of which can also
participate in hydrogen bonds.
• The side chain of cysteine contains a sulfhydryl group (–SH), which
is an important component of the active site of many enzymes

27. Polar Amino Acids
Uncharged

28. Polar Amino Acids
ACIDIC

29. Polar Amino Acids
BASIC

30. Optical properties of amino acids
• The α-carbon of an amino acid is attached to four different chemical
groups and is, therefore, a chiral or optically active carbon atom.
• Glycine is the exception because its α-carbon has two hydrogen
substituents and, therefore, is optically inactive. Amino acids that have
an asymmetric center at the α-carbon can exist in two forms, designated
D and L, that are mirror images of each other.
• The two forms in each pair are termed stereoisomers, optical isomers,
or enantiomers. All amino acids found in proteins are of the L-
configuration. However, D-amino acids are found in some antibiotics
and in plant and bacterial cell walls.

31. Optical properties of amino acids

32. • In nutrition, amino acids are classified as either essential or non-
essential. These classifications resulted from early studies on human
nutrition, which showed that specific amino acids were required for
growth or nitrogen balance even when there is an adequate amount of
alternative amino acids.
• Nonessential amino acids can be made by the body, while essential
amino acids cannot be made by the body so you must get them from
your diet.
• You must have all of the amino acids so your body can build the wide
variety of proteins it needs.
Dietary classification of Amino Acids

33. Dietary classification of Amino Acids

34. Structure of Proteins
• The 20 amino acids commonly found in proteins are
joined together by peptide bonds.
• The linear sequence of the linked amino acids contains
the information necessary to generate a protein
molecule with a unique three-dimensional shape.
• The complexity of protein structure is best analyzed by
considering the molecule in terms of four organizational
levels, namely, primary, secondary, tertiary, and
quaternary

36. I- Primary structure of proteins
• The sequence of amino acids in a protein is called the primary
structure of the protein.
• Understanding the primary structure of proteins is important because
many genetic diseases result in proteins with abnormal amino acid
sequences, which cause improper folding and loss or impairment of
normal function.
• If the primary structures of the normal and the mutated proteins are
known, this information may be used to diagnose or study the disease.

37. Peptide bond
• In proteins, amino acids are joined
covalently by peptide bonds, which
are amide linkages between the α-
carboxyl group of one amino acid and
the α-amino group of another.
• Peptide bonds are not broken by
conditions that denature proteins,
such as heating or high
concentrations of urea.
• Prolonged exposure to a strong acid
or base at elevated temperatures is
required to hydrolyze these bonds non
enzymically.

38. II- Secondary structure of proteins
• The polypeptide backbone forms regular arrangements of amino acids
that are located near to each other in the linear sequence.
• These arrangements are termed the secondary structure of the
polypeptide.
• The α-helix and β-sheet are examples of secondary structures
frequently encountered in proteins

39. α-Helix
• Several different polypeptide
helices are found in nature, but the
α-helix is the most common.
• It is a spiral structure, consisting of
a tightly packed, coiled polypeptide
backbone core, with the side chains
of the component amino acids
extending outward from the central
axis to avoid interfering sterically
with each other

41. β-Sheet
• The β-sheet is another form of secondary
structure in which all of the peptide bond
components are involved in hydrogen
bonding.
• The surfaces of β-sheets appear
“pleated,” and these structures are,
therefore, often called “β-pleated sheets.”
• When illustrations are made of protein
structure, β-strands are often visualized
as broad arrows

43. • https://www.youtube.com/watch?v=J_KCEDrADwg

45. III- Tertiary structure of proteins
• The tertiary structure of a protein refers
to the overall three-dimensional
arrangement of its polypeptide chain in
space.
• It is generally stabilized by outside polar
hydrophilic hydrogen and ionic bond
interactions, and internal hydrophobic
interactions between nonpolar amino
acid side chains

46. III- Tertiary structure of proteins
• Based upon their tertiary structure, proteins are often divided into
globular or fibrous types.
• Fibrous proteins, like α-keratin, have elongated rope-like structures that
are strong and hydrophobic.
• Globular proteins, like the plasma proteins and the immunoglobulins,
are more spherical and hydrophilic.

49. IV- Quaternary Structure Of Proteins
• Many proteins consist of a single polypeptide chain, and are defined as
monomeric proteins. However, others may consist of two or more
polypeptide chains that may be structurally identical or totally unrelated.
• The arrangement of these polypeptide subunits is called the quaternary
structure of the protein

51. Denaturation of proteins
• Protein denaturation results in the unfolding and disorganization of the
protein’s secondary and tertiary structures, which are not
accompanied by hydrolysis of peptide bonds.
• Denaturing agents include heat, organic solvents, mechanical mixing,
strong acids or bases, detergents, and ions of heavy metals such as
lead and mercury.
• Denaturation may, under ideal conditions, be reversible, in which case
the protein refolds into its original native structure when the denaturing
agent is removed. However, most proteins, once denatured, remain
permanently disordered.

53. Protein Misfolding
• Protein folding is a complex, trial-and-error process that can
sometimes result in improperly folded molecules.
• These misfolded proteins are usually tagged and degraded within the
cell.
• However, this quality control system is not perfect, and intracellular or
extracellular aggregates of misfolded proteins can accumulate,
particularly as individuals age.
• Deposits of these misfolded proteins are associated with a number of
diseases.

54. • Disease can occur when an apparently normal protein assumes a
conformation that is cytotoxic, as in the case of Alzheimer disease and
the transmissible spongiform encephalopathies (TSEs), including
Creutzfeldt-Jakob disease.
• In Alzheimer disease, normal proteins, after abnormal chemical
processing, take on a unique conformational state that leads to the
formation of neurotoxic amyloid protein assemblies consisting of β-
pleated sheets.
• In TSEs, the infective agent is an altered version of a normal prion
protein that acts as a “template” for converting normal protein to the
pathogenic conformation.
Protein Misfolding

57. Structure of Heme
Examples of hemoproteins
Myoglobin
and
Hemoglobin

58. Myoglobin
• Myoglobin, a hemeprotein present in heart and skeletal muscle, functions
both as a reservoir for oxygen, and as an oxygen carrier that increases the
rate of transport of oxygen within the muscle cell.
Myoglobin consists of a
single polypeptide chain that
is structurally similar to the
individual subunit polypeptide
chains of the hemoglobin
molecule.
It is a globular protein.

59. Hemoglobin
• Hemoglobin is found exclusively in red blood cells (RBCs), where its main
function is to transport oxygen (O2) from the lungs to the capillaries of the
tissues.
Hemoglobin A, the major
hemoglobin in adults, is
composed of four polypeptide
chains (two α chains and two β
chains) held together by
noncovalent interactions.
It is a globular protein.

60. Hemoglobinopathies
• Hemoglobinopathies are disorders caused either by production of a
structurally abnormal hemoglobin molecule, synthesis of insufficient
quantities of normal hemoglobin subunits, or, rarely, both.
• The sickling diseases sickle cell anemia (Hb S disease) and
hemoglobin SC disease, as well as hemoglobin C disease and the
thalassemia syndromes are representative hemoglobinopathies that
can have severe clinical consequences.

62. Sickle cell anemia (hemoglobin S disease)
• Sickle cell anemia is a homozygous, recessive disorder. It occurs in
individuals who have inherited two mutant genes (one from each
parent) that code for synthesis of the β chains of the globin molecules.
[Note: The mutant β-globin chain is designated βS, and the resulting
hemoglobin, α2βS2, is referred to as Hb S]. An infant does not begin
showing symptoms of the disease until sufficient Hb F has been
replaced by Hb S so that sickling can occur.
• Heterozygotes have one normal and one sickle cell gene. The blood
cells of such heterozygotes contain both Hb S and Hb A. These
individuals have sickle cell trait. They usually do not show clinical
symptoms and can have a normal life span.

65. Sickle cell anemia is characterized by
lifelong episodes of pain (“crises”),
chronic hemolytic anemia with
associated hyperbilirubinemia, and
increased susceptibility to infections,
usually beginning in early childhood.

66. Hemoglobin C disease
• Hb C is a hemoglobin variant that has a single amino acid substitution
in the sixth position of the β-globin chain. In this case, a lysine is
substituted for the glutamate (as compared with a valine substitution in
Hb S).
• Patients homo-zygous for hemoglobin C generally have a relatively
mild, chronic hemolytic anemia. These patients do not suffer from
infarctive crises, and no specific therapy is required.
• Hemoglobin SC disease is another of the red cell sickling
diseases.
• In this disease, some β-globin chains have the sickle cell mutation,
whereas other β-globin chains carry the mutation found in Hb C
disease.

68. Methemoglobinemia
• Oxidation of the heme component of hemoglobin to the ferric (Fe3+)
state forms methemoglobin, which cannot bind oxygen. This oxidation
may be caused by the action of certain drugs, such as nitrates, or
endogenous products, such as reactive oxygen intermediates. Also,
certain mutations in the α- or β-globin chain promote the formation of
methemoglobin (Hb M).
• The methemoglobinemias are characterized by “chocolate cyanosis” (a
brownish-blue coloration of the skin and mucous membranes) and
chocolate-colored blood, as a result of the dark-colored methemoglobin.
Symptoms are related to the degree of tissue hypoxia, and include
anxiety, headache, and dyspnea. In rare cases, coma and death can
occur. Treatment is with methylene blue, which is oxidized as Fe+3 is
reduced.

70. Thalassemias
• The thalassemias are hereditary hemolytic diseases in which an
imbalance occurs in the synthesis of globin chains.
• As a group, they are the most common single gene disorders in
humans.
• Normally, synthesis of the α- and β-globin chains is coordinated, so
that each α-globin chain has a β-globin chain partner. This leads to the
formation of α2β2 (Hb A).
• In the thalassemias, the synthesis of either the α- or the β-globin chain
is defective

71. Examples of structural proteins
• Collagen and elastin are examples of common, well-characterized
fibrous proteins of the extracellular matrix that serve structural
functions in the body.
• For example, collagen and elastin are found as components of skin,
connective tissue, blood vessel walls, and sclera and cornea of the
eye.
• Each fibrous protein exhibits special mechanical properties, resulting
from its unique structure, which are obtained by combining specific
amino acids into regular, secondary structural elements

72. Collagen
• Collagen is the most abundant protein in the human body. A typical
collagen molecule is a long, rigid structure in which three polypeptides
“α chains” are wound around one another in a rope-like triple helix.
• Collagen molecules contain an abundance of proline, lysine, and
glycine, the latter occurring at every third position in the primary
structure. Collagen also contains hydroxyproline, hydroxylysine, and
glycosylated hydroxylysine, each formed by posttranslational
modification.

73. Elastin
• Elastin is a connective tissue
protein with rubber-like properties
in tissues such as the lung.
• α1-Antitrypsin (α1-AT), produced
primarily by the liver but also by
tissues such as monocytes and
alveolar macrophages, prevents
elastin degradation in the alveolar
walls.
• A deficiency of α1-AT can cause
emphysema and, in some cases,
cirrhosis of the liver.