Proteins: Polymers of Amino Acids

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

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

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

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

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

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

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

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

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

10. 20 different amino acids: many combinations • 8 essential Primary Structure The order of amino acids: Protein sequence Secondary Structure Local conformation, depends on sequence Hierarchy of Protein 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 .