Protein Chemistry Lecture Notes PDF

Field of Medicine Medicine And Surgery Program Lecture : Protein chemistry 1 Dr : Moataz maher Date :10/ 2024 Objectives: By the end of this lecture the student will be able to: 1. Define the peptide bond and illustrate how a peptide bond is formed. 2. Identify biologically a...

Field of Medicine Medicine And Surgery Program Lecture : Protein chemistry 1 Dr : Moataz maher Date :10/ 2024 Objectives: By the end of this lecture the student will be able to: 1. Define the peptide bond and illustrate how a peptide bond is formed. 2. Identify biologically active peptides 3.Classify proteins according to their shape, chemical structure and function.  Proteins and peptides are the same. True /False Peptides and proteins are polymers of amino acids.  1. Peptides/ peptide bond formation A peptide consists of two or more amino acids linked by peptide bonds. The bond between the α- carboxyl group of one amino acid and the α-amino group of another aa. with release of H2O (dehydration reaction). Peptide bonds are not broken by conditions that denature proteins, such as heating.  1a. Peptide Bond The peptide chain has two ends - One end containing an amino group to the left of the chain (N-terminus) - The other contains a carboxyl group to the right of the chain (C-terminus) - Each component amino acid in a polypeptide is called a “residue”  1b. Types of peptides Peptides are classified according to the number of amino acids in the chain into: a. Oligopeptides (contain 2-10 amino acids) Dipeptide: a molecule containing 2 amino acids joined by a peptide bond Tripeptide: a molecule containing 3 amino acids joined by peptide bonds b. Polypeptide: a macromolecule containing many amino acids (up to 50) A polypeptide that contains more than 50 amino acids is known as a protein. Proteins consist of one or more polypeptides.  2a. Biologically active Peptide Name Function Amino Acid Sequence Glutathione (3aa) Antioxidant + acts as cofactor in enzymatic Glu-Cys-Gly reactions (help detoxify chemicals) Thyrotropin releasing Hypothalamic hormone Glu-His-Pro Hormone [TRH] (3aa) (regulates release of thyroid hormones) Angiotensin II (8aa) Increases blood pressure Asp-Arg-Val-Tyr-Ile-His-Pro- (acts on the adrenal gland) Phe Bradykinin (9aa) Hypotensive/Vasodilator Arg-Pro-Pro-Gly-Phe-Ser-Pro- (acts on smooth muscle) Phe-Arg Oxytocin (9aa) Uterus-Contracting Hormone Cys-Tyr-Ile-Gln-Asn-Cys-Pro- (also stimulates lactation) Leu-Gly  2b. Biologically active Polypeptides ✓ Insulin (30 aa and 21 aa) - pancreatic hormone, needed for carbohydrates metabolism, 2 polypeptide chains ✓ Glucagon (29 aa) - pancreatic hormone, opposes action of insulin ✓ Corticotropin (or Adrenocorticotropic hormone (ACTH) (39 aa) – secreted from the anterior pituitary gland hormone in response to stress. It stimulates adrenal cortex to produce glucocorticoids like cortisol.  3. Protein classification 3a. Based on their chemical structure: 1.Simple proteins: They are composed of only amino acid residues. 2.Conjugated proteins: They are combined with non-protein part. e.g. Nucleoprotein, Phosphoprotein, Lipoprotein, Metalloprotein…. 3.Derived proteins: They are derivatives or degraded products of simple and conjugated proteins. e.g. peptones, peptides.  3. Protein classification 3a. Based on their chemical structure (Conjugated proteins):  3. Protein classification 3b. Based on their shape (Axial Ratio): Axial ratio = ratio of length over width 1. Fibrous protein: 2. Globular protein: - Axial ratio more than 10 - Axial ratio not more than 4. - Polypeptides arranged in long strands - They are compactly folded and or sheets. coiled into spherical or globular - Water insoluble [due to high content form. of hydrophobic amino acid]. - Water soluble - Strong but flexible - e.g. Albumin, Globulin, - e.g. Keratin, Elastin, Collagen. Hemoglobin, Histones.  3. Protein classification (Fibrous proteins) 3b1. Collagen: Collagen in Greek means –Kolla= “glue”, and -gen =“producing”. As boiling of the skin and tendons of horses [or other animals] resulted in glue formation. Collagen is the most abundant protein in mammals, making 25% to 35% of the whole-body protein content. - It can be converted into gelatins by boiling. - It is found predominantly in various connective tissues in the body [mostly in fibrous tissues such as tendons, ligaments, and skin]. - Collagen is a glycoprotein and contains two types of carbohydrate- glucose and galactose. The carbohydrate part forms glycosidic bond with the hydroxylysine residues.  3. Protein classification (Fibrous proteins) 3b1. Collagen: - Collagen is very rich in glycine (~33% ), proline, hydroxyproline, hydroxylysine (21%) and alanine (11%). - Hydroxylation of proline and lysine are post- translational reactions and require the co-factors [ferrous ion, and vitamin C]. - The amino acid sequence in collagen is a repeating tripeptide unit: (Gly-X- Y). Glycine occurs every third residue while X and Y can be any amino [mostly X positions are proline and Y positions are hydroxyproline].  3. Protein classification (Fibrous proteins) 3b1. Collagen: - The basic structural unit of collagen is tropocollagen. - The tropocollagen subunit consists of three separate polypeptide chains [triple helix]. - There are different types of collagen (~19) and over 90% of the collagen in the human body is type I.  3. Protein classification (Fibrous proteins) 3b1. Collagen: Disorders of Collagen: (1) Scurvy: It is a nutritional disorder caused by a deficiency of vitamin C. This vitamin is important for hydroxylation reactions of lysine and proline (by the enzymes lysyl hydroxylase and prolyl hydroxylase). Defect in hydroxylation causes loss of collagen stability. The formed tropocollagen is unstable and easily degraded. (2) Osteogenesis imperfecta: It is a genetic disorder resulting into fragile bones with skeletal deformities (bone that easily bend and fracture]. The common cause is mutation resulting into replacement of glycine by another bulky amino acid, affecting the triple helix formation. Scurvy:  3. Protein classification (Fibrous proteins) 3b2. Elastin: – It is similar to collagens but cannot be converted to gelatins by boiling. – Elastin is present with collagen in connective tissues and it is the major component of elastic fibers. – Elastin fibers are highly stretchable and has high elasticity, so elastic fibers allow tissues to expand and contract. Tissues rich in elastic fibers include the aorta and other vascular connective tissues, various ligaments and the lungs. – Elastin gives these tissues the property of stretching without tearing (e.g. blood vessels contract in response to the changes in intravascular pressure; the lungs stretch with inhalation and return to their original shape with each exhalation).  3. Protein classification (Fibrous proteins) 3b2. Elastin: - The basic subunit of elastin is tropoelastin. - It is rich in proline and lysine, but contains little hydroxyproline.  3. Protein classification (Fibrous proteins) 3b3. α-keratin: - It is the key structural element making up hair, nails, horns, claws, hooves, and the outer layer of skin. - It is rich in cysteine residues with high percentage of covalent disulfide bonds giving strength to keratin fibers.  3. Protein classification 3c. Based on their Function: Proteins serve in many roles in the body: They act as structural components such as keratin of hair and nail, collagen of bone. They have catalytic function acting as enzymes for almost all reactions in the body They transport important molecules in blood, e.g. oxygen and carbon dioxide by hemoglobin. They have regulatory function as many proteins are hormones and receptors. They are involved in blood clotting through thrombin, fibrinogen and other protein factors. They act as the defense against infections by means of antibodies. Actin, myosin act as contractile protein important for muscle contraction  SUMMARY A peptide consists of two or more amino acids linked by peptide bonds. Peptide bond is formed between the carboxyl group of one amino acid and the amino group of another. Biologically active peptides perform important function in the body [e.g. glutathione and hormones like insulin and glucagon] Protein are classified according to their chemical structure [simple, conjugated and derived], their shape [fibrous & globular] and their function.  Reference: – Lippincott's Illustrated Reviews: Biochemistry, 7th Edition. Chapter 2, pp 45- 47, Chapter 4, pp 134- 158. Best wishes