Chemistry of protein

Chemistry of protein
Biological roles of proteins

1. 1

Chemistry of protein
◘ what are the objective of biochemistry ?
• The major objective of biochemistry is the complete understanding, at the molecular
level, of all of the chemical processes associated with living cells.
◘ why is the study of biochemistry important in medicine ?
• a sound knowledge of biochemistry is essential for talking two main
objectives of the medical sciences :-
1- The understanding and maintenance of health .
2- The understanding and effective treatment of diseases .
◘ Biochemistry & Medicine :-
• Note that :
- Sickle cell anemia is a genetic disease and that both atherosclerosis and
diabetes mellitus have genetic components .

2. 2

◘ The major causes of diseases
•All of the causes listed act by influencing the various biochemical
mechanisms in the cell or in the body :
♦ Physical Agents :

- Mechanical trauma
- Extremes of temperature
- Sudden changes in atmospheric
pressure
- Radiation
- Electric shock

♦ Chemical Agents :

- Drugs
- Certain toxic compounds
- Therapeutic drugs

♦ Biologic Agents :

- Viruses
- Bactria
- Fungi
- Higher forms of parasites

♦ Oxygen lack :

- Loss of blood supply
- Depletion of the oxygen-
carrying capacity of the blood
- Poisoning of the oxidative
enzymes

♦ Genetic disorders :

- Congenital
- Molecular
♦ Immunologic reactions :

- Anaphylaxis
- Autoimmune disease

♦ Nutritional Imbalances :

- Deficiencies
- Excesses

♦ Endocrine Imbalances :

- Hormonal deficiencies
- Hormonal Excesses

3. 3










◘ Proteins :
• Provide the structure of living things .
• Proteins are the most abundant biomolecules in cells & constitute 50 % of
the dry weight of most organisms .
• There are thousands of different kinds of proteins in the cell, each carrying
out a specific function .
• Proteins are thus not only the most abundant but also the most versatile in
functions .
• All proteins in all species , regardless of their function or biological
activity, are built from the same basic set of 20 standard amino acids.
• Proteins may be defined as compounds of high M.W. range from 5000-
25,000,000 and consists of α-amino acids .

4. 4

◘ Biological roles of proteins :
♦ Why proteins are so important ?
♠ Protein Functions :
• Growth , Maintenance & repair for body tissues .
- Building materials : amino acids.
- Structural and mechanical support : Keratin , Collagen , Elastin .
• Energy & Glucose :
- 4 calories per gram .
• Regulatory Roles :
- Enzymes
- Hormones
- Transportation
- Cell receptors
• Regulation of fluid balance :
- Acid-base regulation ( buffer )
• Antibodies & Neurotransmitters

5. 5

◘ Amino acids building blocks of proteins

♦ Structure of Amino acids :
• The α-carbon of all amino acids found in proteins ( with the exception of
glycine ) has four different groups substituted on it; a Carboxyl group, and
Amino group and R group and a Hydrogen atom .
♦ How do amino acids exist in neutral aqueous solution ?
☺in neutral aqueous solution :
• Nonionic form :
- Non-polar amino acids having a single amino
group and a single carboxyl group .
• Zwitter ionic form :
- Exist in neutral aqueous solution as a
fully ionized species called a zwitter ion
( also called dipolar ion ) .
◘ What is meant by Isoelectric point of an amino acid ?
• The pH at which an amino acid exist completely in its zwitter ion state with
no net electric charge on it is isoelectric pH or isoelectric point.
• Molecules of an amino acid at this pH will not move in an electric field .

6. 6

☺ In Alkaline & Acidic solution :
• Because amino acids exist as dipolar ions, they can act both as acids (
proton donors ) or bases ( proton acceptors) .
♦ As an Acid in alkaline solution ♦ As Base in Acidic solution :

◘ Proteinogenic amino acid or common amino acid
♦ Classification of common amino acids :
• The classification of L-α-amino acids depends upon the following
1- Their chemical structure ( Chemical classification )
2- Their nutritional importance ( Nutritional classification )
3- Their metabolic fate ( Metabolic classification )
4- The polarities of their R groups

7. 7

8. 8

◘ Nutritional Classification :
♦ Included :
1- ( Essential Amino acids )
• These include amino acids, which can not be synthesized inside the body.
• Therefore, they must be supplied in the diet, their deficiency leads to
malnutrition.
• They include 10 Amino acids
2- ( Non-Essential Amino acids )
• These amino acids can be synthesized in the body from intermediary
metabolism.
• Their dietary shortage is not accompanied by manifestations of protein
deficiency .

9. 9

◘ Non proteinogenic Amino acid :
• In addition to the 20 proteinogenic amino acids, there also many more
compounds of the same type in nature.
• these arise during metabolic reactions ( A ).
A. Rare amino acids







• Or as result of enzymatic modifications of amino acid residue in peptides or
proteins ( B ).
B. Post translational protein modification

10. 10

• The “biogenic amines” ( C ) are synthesized from α-amino acids by
decarboxylation .
C. Biogenic Amines

11. 11

◘ Non proteinogenic Amino acid or Uncommon Amino acids
• Among these uncommon amino acids are
♦ Hydroxylated amino acids :

- Both are found in collagen, a fibrous protein of connective tissues .
♦ Methylated amino acids :

- 6-N Methyl-lysin is a constituent of myosin, a contractile protein of
muscle .
♦ Carboxylated amino acids :

- Found in the blood clotting protein prothreombin and in certain other
proteins that bind Ca
2+
as part of their biological function .

12. 12

♦ Phosphorylated amino acids :

- Phosphorylation of the –OH groups of serine, threonine, and tyrosine
residues found in certain proteins involved in cell growth and regulation
♦ Iodinated amino acids :

13. 13

♦ Ornithine & Citrulline :

- Ornithine and Citrulline deserve special note because they are key
intermediated ( metabolites ) in the biosynthesis of arginine and in the
urea cycle .
◘ Amino acids not found in proteins :
♦ Decarboxylated amino acids :

- γ- Aminobutyric acid, or GABA, is produced by the decarboxylation of
glutamic acid and is a potent neurotransmitter .

14. 14

♦ Histamine & Serotonin :

- Histamine, which is synthesized by decarboxylation of histidine, and
serotonin, which is derived from tryptophan, similarly functions as
neurotransmitters and regulators .

15. 15

◘ How amino acids link ?

♦ Dipeptide :

- Artificial sweetener, 200 times sweeter than sugar .
♦ Note :
• All protein :
- Are long chains of amino acids.
- Are held together by covalent bonds called peptide bonds .

16. 16

◘ Chemical reaction of amino acids due to NH2 group
♦ In liver ( Detoxification )


- This reaction used for liver function or to excreting toxins from the
body .
♦ Oxidative deamination :

- Play important role in metabolism .
- Synthesis of NH3 in the body .

17. 17

♠ Determination of the amino terminal residue of a polypeptide
♦ Example 1 ( Sanger reaction )
1- Labeling :

2- Hydrolysis :

18. 18

♦ Example 2 ( Edman degradation )
1- Labeling


2- Hydrolysis

- Identify amino-terminal residue; purify and recycle remaining peptide
fragment through Edman process .
Shortened peptide

19. 19

◘ Chemical reaction of amino acids due to COOH group :
♦ Decarboxylation :

- GABA : γ-Aminobutyric acid : this is formed in the brain by
decarboxylation of glutamic acid, where it may act as a chemical
mediator in the transmission of nerve impulse between some neurons .


- Histamine : arise from Histidine by decarboxylation.
- It is a casodilator and is involved in shock and allergic responses .
♦ with NH3 to form amide : ( Detoxification )

- eg : Asparagine and glutamine

20. 20

◘ Do peptides occur in free form in living matter ?
• In assition to the peptides formed as products of partial hydrolysis of
proteins, many peptides occur in the free form in living matter.
• Many of these have intense biologic activity and thus serve important
functions .
• Examples are :
1- Insulin ( Hypoglycemic hormone )
- A hormone secteted by the β-cells of the pancreas , consists of two chains,
with a total of 51 residues, and stimulates the capacity of cells to use
gluscose as metabolic fuel .

2- Glucagon ( Hyperglycemic hormon )
- A hormone secreted by the α-cells of the pancreas, consists of 29 residues,
and opposes the action of insulin.
3- Corticotrophin
- A hormon of the anterior pituitary consists of 39 residues, stimulates
adrenal cortex .

21. 21

4- Oxytocin
- A hormone secreted by the posterio pituitary that stimulates uterine
contractions ( act as antidiuretic hormone ), contain 8 residues of which the
C-terminal glycyl carboxyl is amidated .

5- Polypeptide antibiotics ( from fungi )
- These contain both D- and L- amino acids and amino acids which are not
present in proteins .
- Examples includes : Tyrocidin and Gramicidine S.
6- Bradykini
- A hormone that inhibits inflammation of tissues, and regulate blood
pressure, consist of 9 residues .

7- Thyrotropin ( releasing factor ( TRF ) )
- A tripeptide formed by the hypothalamus stimulates the release of
thyrotropin from the anterior pituitary gland.
- The N-terminal glutamate is cyclised to pyro-glutamic acid and the C-
terminal prolyl carboxyl is amidated .

22. 22

8- Glutathione
- A typical tripeptide in which the N-terminal glutamate is linked to cycteine
via a non-peptide bond, present in all forms of life, reqiured for action of
several enzymes .


- Function of glutathione :
• Serve as a component of an amino acid transport system .
• An activator of certain enzymes ( acting as co-enzyme for
transhydrogenases e.g. glutathione insulin transhydrogenase ) .
• Protection of lipids against autooxidation .

23. 23

♦ Glutathione is an Antioxidant :
• It maintains the SH group of many enzymes .

• It protects hemoglobin against oxidation by hydrogen peroxide ( H2O2 ) .
• It protects the cell membrane of RBCs against hemolysis by oxidizing
agents . e.g., H2O2 .

• Play important role in detoxification reaction :

24. 24

◘ Orders of protein structure
• Four levels of protein structure are commonly drfined
1- Primary Structure
2- Secondary Structure
3- Tertiary Structure
4- Quaternary Structure
♦ Primary Structure :
• Refers to the covalent backbone of the polypeptide chains, including the
sequence of amino acid residues .
♦ Secondary Structure :
• Refers to a regular, recurring arrangement in space of the polypeptide chain
along one dimension .
• OR , refers to regularly coiled or zigzag arrangements of polypeptide
chains along one dimension ( Fibrous proteins are typical 2ry structure ).
♦ Tertiary Structure :
• Refers to how the polypeptide chain is folded in three dimension, to form
the compact, tightly folded structure of globular proteins are spherical in
shapes consisting of amount of coils with no regular structure .
♦ Quaternary Structure :
• In proteins containing more than one polypeptide chain, the number as well
as the arrangement of the subunits is called the quaternary structure .
• The subunits are usually held together by non-covalent bonds (hydrophobic
interactions, hydrogen and ionic bonds).

25. 25

◘Secondary Structure
♦ Protein Folding :
• 2 regular folding patterns have been identified – formed between the bonds
of the peptide backbone .
• α-helix : protein turns like a spiral-fibrous proteins ( hair, nails , horns ).
• β-sheet : protein folds back on itself as in a
ribbon-globular protein .
♠ α-helix :
- Formed by a H-bond between every 4
th
peptide
bond –C=O to N-H .
- Usually in proteins that span a membrane .
- The α-helix can either coil to the right or the left
- form structural proteins such as nails and skin .
♠ β-sheet :
- Core of many proteins is the β-sheet .
- Form rigid structures with the H-bond.
- Can be of 2 types :
1- Anti-parallel : Run in an opposite
direction of its neighbor (A) .

26. 26

2- Parallel : run in the same direction with longer looping sections between
them ( B ) .

Lec. Done Q.A ☺ ♥