Peptides, Polypeptides & Biochemical Importance PDF

# Peptides, Polypeptides & Biochemical Importance ## Learning Objectives - By the end of the lecture students will be able to define: - Peptides - Polypeptides - Types - Biochemical Function ## Your patient - A 16-year-old boy working as a mason presents with a history of polyuri...

# Peptides, Polypeptides & Biochemical Importance ## Learning Objectives - By the end of the lecture students will be able to define: - Peptides - Polypeptides - Types - Biochemical Function ## Your patient - A 16-year-old boy working as a mason presents with a history of polyuria, polydipsia, and weight loss of 6 kg over 3 months. His biochemical evaluation shows fasting plasma glucose - 280 mg/dl, postprandial plasma glucose - 380 mg/dl, HbA1c - 10.5%, and glutamic acid decarboxylase antibody positive. How would you manage? - A 38-year-old woman diagnosed to have type 2 diabetes for 6 years, well-controlled on tablet metformin 1 mg twice daily and tablet gliclazide 40 mg twice daily, is admitted with autoimmune hemolytic anemia. She is now started on tablet prednisolone 60 mg/day. Blood glucose monitoring in the ward shows fasting glucose of 360 mg/dl and postprandial glucose of 420 mg/dl, with negative urine ketones. What would you advise? ## Peptides - Peptides are form, when less than 50 amino acid join together through a peptide bond. OR - Peptides are short polymers of amino acid usually monomers linked by peptide bonds the covalent chemical bonds formed between two molecules. - When the carboxyl group of one molecule reacts with the amino group of other molecule The image shows a diagram of proteins are chains of amino acids. - Short chains of amino acids are called peptides. - Peptides of more than 10 amino acids residues are called polypeptides. ## Peptide/Polypeptides - Peptides are polymers of amino acids. - Peptides are small condensation products of amino acids. - Their structure and functions depend upon: - Nature of amino acids present in them - Sequence of amino acids - Spatial relationship of amino acids. - Many peptides are formed from breakdown of proteins - Peptides are relatively small polymers, 2-10 amino acid unit. If 2 amino acids were involved then called Dipeptide viz, tripeptide for 3 amino acid unit and Decapeptide for 10 unit. - Oligopeptide: a few amino acids - Big peptides are called polypeptides more than 50 amino acids - Polypeptide: many amino acids ## Types - The shortest peptide is DIPEPTIDE made up of two amino acids joint together by peptide bond to form a dipeptide molecules. - Tripeptide - Tetra etc. etc. The image shows a diagram of a tetrapeptide (example Val-Gly-Ser-Ala) with green marked amino end (L-Valine) and blue marked carboxyl end (L-Alanine). - Peptides of defined length are named using IUPAC numerical multiplier prefixes: - A monopeptide has one amino acid. - A dipeptide has two amino acids. - A tripeptide has three amino acids. - A tetrapeptide has four amino acids. - A pentapeptide has five amino acids. - A hexapeptide has six amino acids. - A heptapeptide has seven amino acids. - An octapeptide has eight amino acids (e.g., angiotensin II). - A nonapeptide has nine amino acids (e.g., oxytocin). - A decapeptide has ten amino acids (e.g., gonadotropin-releasing hormone & angiotensin I). ## Functions of Peptides - Hormones and pheromones - Insulin (sugar uptake) - Oxytocin (childbirth) - Sex-peptide (fruit fly mating) - Neuropeptides - Substance P (pain mediator) - Antibiotics - Polymyxin B (for Gram bacteria) - Bacitracin (for Gram bacteria) - Protection, e.g. toxins - Amanitin (mushrooms) - Conotoxin (cone snails) - Chlorotoxin (scorpions) The image shows a list of biologically important peptides - Glutathione - Thyrotropin releasing hormone (TRH) - Oxytocin - Vasopressin - Angiotenins - Bradykinin - Methionine enkephalin ## Polypeptide - Poly mean MANY - A polypeptide is a long, continuous and unbranched peptide - Proteins consists of one or more polypeptides arranged in a biologically functional way and are often bound to cofactors or other proteins. The image shows a diagram of a large number of amino acids linked to form protein: Amino acids are linked by a covalent bond called peptide bonds. ## Peptide Bond - Amino acids are attached covalently by aCOOH group on one side and aNH2 group on another side. - Now there is formation of ACID-AMIDE BOND===PEPTIDE BOND. The image shows a diagram showing the formation of a dipeptide from two amino acids. The formation of a peptide bond is accompanied by the release of a water molecule. - Peptide bond is formed by condensation reaction: Water molecule is removed, two amino acids linked The image shows a 3d model diagram of a peptide bond. The bond angle is about 120°. - Peptide Bond Formation - Amino acids are linked together by condensation reaction between carboxylic and amino groups from two different amino acids (with elimination of water). - The amide bond formed is called peptide bond. - The product is called a peptide, and named according to the number of amino acids involved: e.g. dipeptide (2), tripeptide (3), decapeptide (10). - Big peptides (> 50 amino acids) are called polypeptides. ## Characteristics of Peptide Bonds - Peptide bonds are strong with partial double bond character: - They are not broken by usual denaturing agents like heating or high salt concentration. - They can be broken by: - Prolonged exposure to strong acid or base at elevated temperatures. - Specific enzymes such as digestive enzymes. - Peptide bonds are rigid and planner resisting free rotation, therefore they stabilize protein structure - Peptide bonds are uncharged but polar. - Peptide bonds contain polar hydrogen atoms of amino groups (with a partial positive charge) and polar oxygen atoms of carboxyl groups (with a partial negative charge). - This allows hydrogen bonds to form between peptide bonds in different parts of the chain. ## Individual Peptides - Peptides are widespread in nature. - They are often involved in specific biological activities (peptide hormones, peptide toxins, peptide antibiotics). - Thyrotropin releasing hormone (TRH) is a tripeptide with the sequence of Glu-His-Pro; but the Glu is modified to form pyroglutamic acid. - Oxytocin and Vasopressin (ADH) are nanopeptides; with 9 amino acids. They are secreted by posterior pituitary. - Angiotensin I has 10 amino acids and Angiotensin II has 8 amino acids. They cause hypertension. The image shows a diagram of glutathione (L-glutamyl-L-cysteinyl-glycine) which is widespread in animals, plants and microorganisms. - Beef (200), broccoli (140), spinach (120), chicken (95), potatoes (71), paprika (49), tomatoes (49) and oranges (40) are especially rich in glutathione (mg/kg). - A noteworthy feature is the binding of glutamic acid through its carboxyl group. - The peptide is the coenzyme of glyoxalase - Cysteine, glycine, and glutamine - and is produced naturally in the body. It is called the master antioxidant because it can regenerate itself in the liver after each "fill-up" of free radicals and go back to work. - ↑ glutathione levels ↓ muscle damage, ↓ recovery time, ↑ strength and endurance, and shift metabolism from fat production to muscle development. - Glutathione is critical in helping the body's first line of defense against disease and illness - the immune system The image shows a diagram of 2-lysine peptides. - A number of peptides including lysine (Gly-Lys, Ala-Lys, Glu-Lys, Lys, Lys, Gly-Lys Gly) have been shown to be as good as lysine in rat growth feeding tests. - These peptides substantially retard and delay the browning reaction with glucose, hence they are suitable for lysine fortification of sugar-containing foods which must be heat treated. The image shows a diagram of nisin (a peptide from Streptococcus lactis) which contains unusual amino acids (dehydroalanine, dehydro-ß-methyl-alanine, lanthionine, ß-methyl-lanthionine) and five thioether bridges. - This peptide is formed by several strains of Streptococcus lactis. - It contains a number of unusual amino acids, namely dehydroalanine, dehydro-ß-methyl-alanine, lanthionine, ß-methyl-lanthionine, and therefore also five thioether bridges. - Nisin is active against Gram-positive microorganisms (lactic acid bacteria, Streptococci, Bacilli, Clostridia). - Nisin begins to act against the cytoplasmic membrane as soon as the spore has germinated. Hence, its action is more pronounced against spores than against vegetative cells. - Nisin is permitted as a preservative in several countries. It is used to suppress anaerobes in cheese and cheese products, especially in hard cheese and processed cheese to inhibit butyric acid fermentation. - The use of nisin in the canning of vegetables allows mild sterilization conditions. The image shows a diagram of carnosine, anserine and balenine (peptides present in meat extract) which are noteworthy as they contain a ß-amino acid, ß-alanine, bound to L-histidine or 1-methyl- or 3-ethyl-L-histidine. - These peptides are noteworthy since they contain a ß-amino acid, ß-alanine, bound to L-histidine or 1-methyl- or 3-ethyl-L-histidine, and are present in meat extract. - Many peptides that are released in vitro or in vivo from animal or plant proteins are bioactive and have health-promoting functions in humans beyond normal and adequate nutrition. - Different health effects have been attributed to food-derived peptides, including antimicrobial properties, blood pressure-lowering effects, cholesterol-lowering ability, antioxidant activities, enhancement of mineral absorption and/or bioavailability and cyto- or immuno-modulatory effects. - Numerous products are already on the market or under development by food companies that exploit the potential of food-derived bioactive peptides which ascribe scientifically evidenced health claims to consumption of these functional foods. The image shows a diagram of an overview of beneficial effects of bioactive peptides from food proteins: - A wide range of activities has been described, including antimicrobial properties, blood pressure-lowering effects, cholesterol-lowering ability, antioxidant activities and enhancement of mineral absorption/bioavailability. - Moreover, some peptides are multi-functional and can exert more than one of the effects mentioned. The image shows a diagram of antimicrobial peptides - Antimicrobial peptides have been identified from many protein hydrolysates, especially from milk. - The most well studied are the lactoferricins, which are derived from bovine and human lactoferrin. - Additionally, a few antibacterial peptides have been identified from a51-casein and a52-casein. - Antimicrobial peptides act against different Gram-positive and Gram-negative bacteria (Escherichia, Helicobacter, Listeria, Salmonella and Staphylococcus), yeasts and fungi. - The disruption of normal membrane permeability is at least partly responsible for the antibacterial mechanism of lactoferricins. The image shows a diagram of antioxidant peptides - Antioxidant properties that prevent enzymatic (lipoxygenase) and non-enzymatic peroxidation of essential fatty acids have been found in peptides derived from milk proteins. - Most of the peptides identified are encoded in the sequence of a-casein. - The addition of a leucine or proline residue to the Nterminus of a His-His dipeptide, for example, can enhance antioxidant activity and facilitate further synergy with non-peptide antioxidants like BHT or BHA (synthetic antioxidants). The image shows a diagram of Food Applications of Bioactive Peptides - A large number of the bioactive peptides found naturally in traditional foods that have been consumed long before the term 'bioactive' was established. - Many of these peptides are released from the host proteins by fermentation of milk, including cheese ripening. - Many peptides are generated by enzymatic reactions in the gut after ingestion of foods containing precursor proteins (e.g. after drinking a glass of milk). The image shows a diagram of Peptides in molecular biology - Peptides have recently received importance in molecular biology for several reasons. - The first is that peptides allow the creation of peptide antibodies in animals without the need to purify the protein of interest. This involves synthesizing antigenic peptides of sections of the protein of interest. These will then be used to make antibodies in a rabbit or mouse against the protein. - Another reason is that peptides have become instrumental in mass spectrometry, allowing the identification of proteins of interest based on peptide masses and sequence. In this case, the peptides are most often generated by in-gel digestion after electrophoric separation of the proteins. - Peptides have recently been used in the study of protein structure and function. - For example, synthetic peptides can be used as probes to see where protein-peptide interactions occur. - Inhibitory peptides are also used in clinical research to examine the effects of peptides on the inhibition of cancer proteins and other diseases. The image shows a diagram of C-PEPTIDE - Patients with diabetes may have their C-peptide levels measured as a means of distinguishing type 1 diabetes from type 2 diabetes or Maturity onset diabetes of the young. - Differential diagnosis of hypoglycemia - C-peptide levels may be checked in women with Polycystic Ovarian Syndrome (PCOS) to help determine degree of insulin resistance - used for determining the possibility of gastrinomas associated with Multiple Endocrine Neoplasm syndromes (gastrinoma is a tumor in the pancreas or duodenum) - Measuring C-peptide levels will help differentiate a healthy patient from a diabetic one. The image shows a list of antimicrobial peptides used as therapeutic agents - Antimicrobial peptides have been used as therapeutic agents: - Bacitracin for pneumonia, topical - Boceprevir, Hepatitis C (oral, cyclic peptide) - Dalbavancin, bacterial infections, IV - Daptomycin, bacterial infections, IV - Enfuvirtide, HIV, subcutaneous injection - Oritavancin, bacterial infections, IV - Teicoplanin, bacterial infections, IV - Telaprevir, Hepatitis C, oral cyclic peptide - Telavancin, bacterial infection, IV - Vancomycin, bacterial infection, IV. - Guavanin 2, bacterial infection against Gram-positive and Gram-negative also The image shows a list of the benefits of collagen peptides - Benefits of collagen peptides (Therapeutic) - Improve joint health - Support bone strength - Promote healthy aging - Boost skin beauty - Support connective tissues and prevent injuries - And many more health benefits - Brain Peptides: Certain brain cells have receptors that bind opiates like morphine and have been termed endorphins (endogeneous morphine). Dynorphin is a peptide of 13 amino acids which is called superopioate since it is significantly potent. Peptide fragments from brain that reduce intestinal motility are met-enkephalins and leuenkephalin both pentapeptides. - Doping test (Sports Medicine): The term peptide has been used to mean secretagogue peptides and peptide hormones in sports doping matters (Secretagogue are substances that causes another substance to release) The image shows a diagram of Proteins can be functionally classified. - Enzyme: Protease Degrades Protein - Defense: Antibody Fights Viruses. - Contractile: Actin & Myosin Contracts Muscle Fibers - Regulation: Insulin Controls Blood Glucose - Transportation: Hemoglobin Carries O₂ - Support: Keratin & Collagen Forms Hair and Nails.