1. Proteins: Polymers of Amino Acids
20 different amino acids: many combinations
Proteins are made in the RIBOSOME

2. Amino Acid Chemistry NH2 Ca R COOH H NH2 Ca R1 COOH H R2 NH2 Ca R1 CO
20 different types
NH2 Ca R
COOH H
amino
acid
NH2 Ca R1
COOH H R2
NH2 Ca R1 CO H NH R2
COOH
Amino acid
Polypeptide
Protein

3. The free amino and carboxylic acid groups have pKa’s
Amino Acid Chemistry
NH2 Ca R
COOH H
amino
acid
The free amino and carboxylic acid groups have pKa’s
NH2
NH3+
pKa ~ 9.4
COOH
COO-
pKa ~ 2.2
At physiological pH, amino acids are zwitterions
+NH3 Ca R
COO- H

4. Also titratable groups in side chain
Amino Acid Chemistry
Also titratable groups in side chain
Note the axes

5. Amino Acids with Aliphatic R-Groups
Glycine
Gly - G
                                     
2.4
9.8
Alanine
Ala - A
                                         
9.9
Valine
Val - V
                                                        
2.2
9.7
Leucine
Leu - L
                                                                       
2.3
Isoleucine
Ile - I
                                                                 
pKa’s

6. Amino Acids with Polar R-Groups
Non-Aromatic Amino Acids with Hydroxyl R-Groups
Serine
Ser - S
                                                           
2.2
9.2
~13
Threonine
Thr - T
                                                        
2.1
9.1
Amino Acids with Sulfur-Containing R-Groups
Cysteine
Cys - C
                                                          
1.9
10.8
8.3
Methionine
Met-M
                                                             
9.3

7. Acidic Amino Acids and Amide Conjugates
Aspartic Acid
Asp - D
                                                                 
2.0
9.9
3.9
Asparagine
Asn - N
                                                                   
2.1
8.8
Glutamic Acid
Glu - E
                                                                            
9.5
4.1
Glutamine
Gln - Q
                                                                                
2.2
9.1

8. Basic Amino Acids Arginine Arg - R 1.8 9.0 Lysine Lys - K 2.2 9.2
                                                                                    
1.8
9.0
12.5
Lysine
Lys - K
                                                                             
2.2
9.2
10.8
Histidine
His - H
                                                                 
6.0

9. Aromatic Amino Acids and Proline
Phenylalanine
Phe - F
                                                             
2.2
9.2
Tyrosine
Tyr - Y
                                                                        
9.1
10.1
Tryptophan
Trp-W
                                                                      
2.4
9.4
Proline
Pro - P
                             
2.0
10.6

10. Hierarchy of Protein Structure
20 different amino acids: many combinations
8 essential
The order of amino acids: Protein sequence
Primary Structure
Local conformation, depends on sequence
Secondary Structure
Tertiary/Quaternary Structure
Overall structure of the chain(s) in full 3D

11. Binding Classification of Proteins
Structural- other structural proteins
Receptors- regulatory proteins, transmitters
Toxins- receptors
Transport- O2/CO2, cholesterol, metals, sugars
Storage- metals, amino acids,
Enzymes- substrates, inhibitors, co-factors
Cell function- proteins, RNA, DNA, metals, ions
Immune response- foreign matter (antigens)

12. Classification Essential amino acids:
There are amino acids that cannot be synthesized in the body.
They must be taken in diet.
Their deficiency affects growth , health and proteins synthesis.

15. Half essential amino acids
These amino acids are synthesized in the body in amount enough for adults , but not for growing children.
Arginine
Histidine

16. Arginine is very popular among athletes and bodybuilders because it is required in muscle metabolism – maintaining the nitrogen balance, and helping with weight control since it facilitates the increase of muscle mass, while reducing body fat.

18. Non essential amino acids
These are the rest of amino acids which are synthesized in the body , mostly from carbohydrates, in amount enough for adults and growing children.

19. Metabolic classification
Ketogenic amino acids: which gives both ketone ketones bodies. Leucine is the only ketogenic amino acids.

20. People with liver and kidney problems can also benefit form L-Leucine supplementation because it can enhance liver protein synthesis and improve breathing ability and quality of sleep for those with kidney disorders.
Finally, L-Leucine may lower blood sugar levels and normalize and control insulin release and insulin function. Because of this, diabetics may find L-Leucine a helpful addition to their disease management program.

21. Glucogenic and ketogenic amino acids
Which give both ketone bodies and glucose are:
Phenylalanine
Tyrosine
Tryptopohan
Lysine
Isoleucine

22. Functions of amino acids
Body peptides and proteins: E.g plasma proteins , tissue proteins, enzymes etc
Hormones: Some hormones are amino acids derivatives. E.g thyrosine and catecholamines.
Amines: Some amino acids give corresponding amines by decarboxylation e.g histidine gives histamine which is vasodilator.

23. Cont.
Neurotransmitters: Some amino acids, glutamate acts as neurotransmitters.
Detoxification: Some amino acids are used detoxification reaction e.g glycine
Health and growth: Essential amino acids support growth in infants and maintain health in adults.

24. physical properties
Solubility: Soluble in water, dilute acids , alkalies and ethanol.
Optical activity: Optically active because they contain asymetric carbon.
Melting point: High ionic forces. Tm 200˚C.

25. Chemical properties
Peptide bond formation.
Properties of R group.

26. Proteins
Proteins are molecules having a very high molecular weight ,ranging from 5,000 to several million.
The term protein is applied to describe molecules greater than 100 a.a
Molecules contain less than 100 a.a are termed :larger polypeptides.

27. Functions Enzymes :all enzymes are proteins
Transport : of small molecules and ions e.g
1. Hemoglobin is a carrier for oxygen.
2. lipoproteins , are carriers of lipids.

28. Structural proteins Cell membrane : Glycoproteins
Skin and bones e.g collagen

29. Hormonal regulation Some hormones are protein in nature e.g insulin.
Cellular receptors that recognise hormones are proteins.

30. Defence mechanism Antibodies (immunoglobulins) are proteins in nature.
Keratin found in skin and tissues is proteins that act against mechanical and chemical injuries.

31. Cont. Blood clotting : coagulation factor
Storage: Ferritin ,which is a storage form of iron.
Control of genetic expression: activator receptors and many regulators of genes are protein in nature.

32. Conformation of proteins
Every protein in its native state has a 3-dimensional structure.(primary, secondary, and tertiary),which is known as conformation . Conformation is essential for the function of each protein. Any change in conformation may lead to disease.

33. Primary proteins
It is a order (arrangement) of amino acids in the polypeptide chain.(chains).
Covalent bond.
Free NH3 and CooH terminals.
The arrangement of amino acids in each protein is determined by the genetic information present in DNA.

34. Secondary proteins
Hydrogen bonds
Two forms alpha and beta form.

35. a Helix
Left-hand a helix
Right-hand a helix

36. Tertiary structure Two types:
Fibrous : which is an extended form e.g keratin ,collagen and elastin.
Globular proteins: which is a compact form and folding of polypeptide chain e.g myoglobin.

37. Quaternary structure
Many proteins are composed of several polypeptide chain .Each polypeptide chain is called subunits.
E.g insulin : 2 subunits
Lactate dehydrogenase enzyme :4 subunits
Globin of haemoglobin:4 subunits.

38. Denaturation of proteins
Def : protein denaturation mean unfolding and loss of secondary ,tertiary and quaternary structure.
1.denaturation does not affect primary structure i.e not accompained by hydrolysis of peptide bonds.
2. denaturation may be reversible( in rare cases)

39. Effect of protein denaturation
Loss of biological activity : insulin looses its activity after denaturaion.
Denaturation proteins are often insoluble.
Denaturation protein are easily precipitated.

40. Denaturation factor Heat Organic solvents Detergent Mechanical mixing
Strong acids and bases
Heavy metals.
Enzymes
Repeated freezing and thawing

41. Classification of proteins
Simple proteins: On hydrolysis they give only amino acids.
Conjugated proteins: give amino acids and non proteins (prosthetic group).
Derived proteins:
1. primary derived proteins : denatured protein
2.secondary derived proteins: product of hydrolysis of simple and conjugated proteins.

42. Simple proteins Albumin and globulin
Scleroproteins : include keratin ,collagen ,elastin,reticulin.

43. Alpha keratin
Found in hair ,nail , enamel of teeth ,and outer layer of skin.
Rich in cysteine
Insoluble due to high content of hydrophobic amino acids

44. collagen Present in skin ,bones , tendons, and blood vessels.
Collagen may be present as a gel e.g in extracellular matrix or in vitreous humor of the eye.

45. collagen diseases
Scurvy; it is due to deficiency in a ascorbic acids (vitamin c).
Ascorbic acids acts as coenzyme in hydroxylation reaction of proline and lysine.
Symptoms: abnormal bone development ,bleeding , loosing of teeth and swollen gums.

46. Cont. Osteogenesis imperfecta:
1. It is a genetic disorders lead to weak bones and skeletal deformities.
2. It is due to mutation in the gene that code for α –chain for collagen.
Ehlers-Danlos syndrome:
Genetic disorder lead to connective tissues disease
Symptoms : stretchy skin and loosed joints.

47. Elastin It is a connective tissue proteins.
Rubber –like, stretched several times
Present in lungs , the walls of large blood vessels and elastic ligaments.

48. Conjugated proteins
On hydrolysis ,they give protein part (apoproteins) and nonproteins part(prosthetic group)

49. phosphoproteins These are protein conjugated with phosphate group.
Phosphate group is attached to –OH group of serine (phosphoserine) or threonine(phosphothreonine) present in protein part. E.g
Caseine :one of the milk protein
Vitellin: present in egg yolk.
Phosphoenzyme: phoephorylation and dephosphorylation.

50. lippoproteins These are proteins conjugated with lipids
Plasma proteins and cell membrane.
Helps water insoluble lipids to transport in blood
Helps water insoluble substance to pass through cell membrane .

51. Glycoproteins and proteoglycans
These are proteins conjugated with carbohydrates in varying amount .i.e 2 to 15 sugar units.e.g blood group, enzyme and mucin
Proteoglycans contain long unbranched chains of sugar units more than 50 units. E.g cell membrane

52. nucleoproteins
These are proteins conjugated with nucleic acid (DNA or RNA ).
1. chromosomes: proteins conjugated with DNA .
2. Ribosomes; proteins conjugated with RNA.

53. Metalloproteins Proteins conjugated with metals
Mettaloproteins containing iron: The iron may be in the form of heme or nonheme iron.
Ferritin : is the storage form of iron ,present in liver ,spleen, bone marrow and intestinal cells.
Transferrin. Is the iron carrier protein in the plasma.
Hemosiderin :iron toxicity (over dosage) as in case of repeated blood transfusion.