Sheet 20 Biochemistry PDF

Duha Alnader&Wedad Mustafa Reem Ghnemat Dr.NafezAbutarboush 1  Fibrous proteins Structure-function relationship: Have hard solid strong structure to aid in support & a special type of secondary structure and has only this type of sec...

Duha Alnader&Wedad Mustafa Reem Ghnemat Dr.NafezAbutarboush 1  Fibrous proteins Structure-function relationship: Have hard solid strong structure to aid in support & a special type of secondary structure and has only this type of secondary structure repeated over and over again so it can be compressed to reduce spaces and expel water forming a strong structure. Have tertiary structure and quaternary structure that consists of more than one polypeptide Biological Functions of Proteins: ▪ Enzymes - catalysts for reactions ▪ Transport molecules - hemoglobin; lipoproteins, channel proteins ▪ Contractile/motion - myosin; actin Structural--collagen; keratin, actin ▪ Defense - antibodies ▪ Signaling -hormones, receptors Toxins—diphtheria(‫ ;)خناق‬enterotoxins Types of proteins ▪ Structure: –Fibrous (fiber-like with a uniform secondary-structure only) -Globular (globe-like with three dimensional compact structures) ▪ Examples ▪ Fibrous proteins: collagens, elastins, and keratins ▪ Globular proteins: myoglobin, hemoglobin, and immunoglobulin. 2  extracellular matrix ▪ The extracellular space is largely filled by an intricate network of macromolecules including proteins and polysaccharides that assemble into an organized meshwork in close association with cell surface. collagen is synthesized by cells and released into ECF, so it’s mainly found in ECF, and it provides general structure of tissues & straightens them. *Collagens accounts for 40% of proteins in our bodies Collagens and their properties ▪ The collagens are a family of fibrous proteins with 25 different types found in all multicellular animals. ▪ They are the most abundant proteins in mammals, constituting 25% of the total protein mass in these animals. ▪ Collagen molecules are named as type I collagen (Most common one, found in bones & cartilages), type II collagen, type III collagen, and so on, these types differ in amino acids comprising them. These types adopt same structural features despite the fact that they differ in sequence of amino acids. ▪ The main function of collagen molecules is to provide structural support to tissues. ▪ Hence, the primary feature of a typical collagen molecule is its stiffness. 3  Structure of collagen ▪ It is a left-handed, triple-stranded, helical protein , in which three collagen polypeptide chains, called α-chains, are wound around one another in a ropelike superhelix. ▪ This basic unit of collagen is called tropocollagen. ▪ Compared to the α-helix, the collagen helix is much more extended with 3.3 residues per turn (more relaxed) collagen is composed of collagen fibers fibrils microfibrils 5 structures of tropocollagen (basic unit) composed of 3 polypeptide chains each adopts a helical shape wound around one another forming repeated knots and widened areas, these knots (hydrophobic interaction) contain glycine molecules (breakers of α-helix) of interacting polypeptide chains. *Every 3 A.A a knot is formed -Not an α-helix since it has glycine which is a breaker of α-helix *Differs from collagen in length 5.4 A & number of amino acids per turn 3.6 A. A: that’s because we call it α-chain -properties of α-helix: Right-handed helix, 3.6 A. A per turn & the length of loop is 5.4 A Composition of collagens ▪ Collagens are rich in glycine (each 3 A.A have glycine) (33%) and proline (13%). -Proline is modified as hydroxyproline creating kinks disrupting helical structure of α-helix ▪ It is also unusual in containing hydroxyproline (9%) and hydroxylysine. 4  ▪ Every third residue is glycine, which, with the preceding residue being proline or hydroxyproline in a repetitive fashion as follows: ▪ Gly-pro-Y ▪ Gly-X-hydroxyproline Functional purpose of amino acids ▪ Glycine allows the three helical of α-chains to pack tightly together to form the final collagen superhelix. ▪ Proline creates the kinks and stabilizes the helical conformation in each a chain. Purpose of hydroxyproline -Which illustrates how structure aid in function ▪ Normal collagen is stable even at 40 °C. ▪H-bonds maintain helical shape without hydrogen bonds between hydroxyproline residues, the collagen helix is unstable and loses most of its helical content at temperatures above 20 °C *hydroxyproline preserves helical shape of collagen through H-bonds(hydrogen bonds are affected by temperature In normal collagen: *At 37 °C , 100% of collagen adopts its helical shape 5 *After 40 °C , denaturation of protein occurs due to loss of H-bonds In abnormal collagen: *At 20 °C , 30% of collagen have its helical shape and as temp. increases it loses its helical shape *At 37 °C , 5% of collagen preserved its helical shape Hydroxylysine (modified lysine) Lysine can be modified by the addition of OH group it either remains as it is or undergoes oxidation forming an aldehyde(OH is oxidized forming Aldehyde) ▪ Hydroxylysine serves as attachment sites of polysaccharides making collagen a glycoprotein. *lysil hydroxylase and lysil oxidase form crosslinks to produce modified lysine *proline hydroxylase-helical-modified proline lysil hydroxylase & proline hydroxylase require vit.C to function Oxidation of lysine ▪ Some of the lysine side chains are oxidized to aldehyde derivatives known as allysine (aldehyde-oxidized form of lysine) ▪ Covalent aldol cross-links form between hydroxylysine residues and lysine or another oxidized lysine,when two aldehyde derivatives meet they form a covalent bond between them ,in other words a covalent bond between two collagen chains or a covalent link between tropocollagen-tropcollagen or an intramolecular covalent link between two helical shapes within the same tropocollagen ,thereby tropocollagens are bound to each other tightly forming a strong protein-collagen 6 Function of cross-linking -purpose of cross linking is to give strength **** For crosslinking to occur we need: Modified lysine formed by two enzymes 1) lysl hydroxylase -hyydroxylates lysine forming hydroxylysine 2) lysl oxidase-converts hydroxylysine into aldehyde (oxidized form of lysine) 3) prolyl hydroxylase -to maintain its helical shape ▪ These cross-links stabilize the side-by side packing of collagen molecules and generate a strong fibril ▪ If cross-linking is inhibited, the tensile strength of the fibrils is drastically reduced; collagenous tissues become fragile, and structures such as skin, tendons, and blood vessels tend to tear. ▪ The amount of cross-linking in a tissue increases with age (cross linking of collagen increases overtime since we need more work & as movement increases). That is why meat from older animals is tougher than meat from younger animals. ▪These cross-links stabilize the side-by side packing of collagen molecules and generate a strong fibril 7  Formation of collagen fibers ▪ Following cellular release of protocollagen, 5 of them polymerize into a microfibril, that get connected with each other via aldehyde links. (cross links) ▪ Microfibrils align with each other forming larger collagen fibrils, which are strengthened by the formation of covalent cross-links between lysine residues. ▪ Microfibrils assemble into collagen fibers. Scurvy (acquired disease) ▪ A disease caused by a dietary deficiency of ascorbic acid (vitamin C) -coenzyme doesn’t add OH group properly to lysine & proline ▪ Deficiency of vitamin C prevents proline hydroxylation& lysine hydroxylation ▪ The defective pro-α chains fail to form a stable triple helix and are immediately degraded within the cell. ▪ Blood vessels become extremely fragile, spontaneous bleeding of gingiva, bruises under skin, and teeth become loose in their sockets. -capillaries become filled with collagen and are easily cut ****** Collagen is present in walls of capillaries and its function in vasculature is to provide strength and prevent tearing of walls 8  Elastins -crosslinks of elastins prevents tearing of tissues when stretched -elastins interwoven with collagen hardening elastic tissue -have weak bonds between small fractions of polypeptides & hydrophobic interaction most of them are non-polar***** Resilience vs. flexibility ▪ Many tissues, such as skin, blood vessels, and lungs, need to be both strong and elastic in order to function. ▪ A network of elastic fibers in the extracellular matrix of these tissues gives them the required resilience so that they can recoil after transient stretch. ▪ Long, inelastic collagen fibrils are interwoven with the elastic fibers to limit the extent of stretching and prevent the tissue from tearing Elastin ▪ The main component of elastic fibers is elastin, which is a highly hydrophobic protein and is rich in proline and glycine and also has lysine & alanine. ▪ It contains some hydroxyproline & lysl oxidase and so have allysine, but doesn’t have lysl hydroxylase ▪ It is not glycosylated. ▪ The primary component (tropoelastin molecules) is cross-linked between lysines to one another 9 *crosslinking occurs between allysine Elastin structure ▪ The elastin protein is composed largely of two types of short segments that alternate along the polypeptide chain: ▪ Hydrophobic segments, which are responsible for the elastic properties of the molecule; and ▪ Alanine- and lysine-rich -helical segments******, which form cross-links between adjacent molecules -Consist of 4 polypeptides three of them have allysine & one of them has unmodified lysine together they form a ring (desmosine) * Three allysyl side chains plus one unaltered lysyl side chain form a desmosine crosslink Keratins -unusal content of cystine forming S-S disulfide bonds -found in nails,hair,horns,skin -as cystine content increases hardness increases - α-helix right-handed,3.6 A.A per turn ,5.4A* ▪ Two important classes of proteins that have similar amino acid sequences and biological function are called α-keratin (in humans) and β-keratins (in birds,reptiles), which as members of a broad group of intermediate filament proteins. ▪ α-keratin is the major proteins of hair and fingernails as well as animal skin. ▪ α-keratin has an unusually high content of cysteine. -Has lower content of cystine Soft -prevalent in our bodies α -keratin Hard 10  Structure ▪ Two helical α-keratin molecules (protofilaments) interwind forming a dimer. ▪ Two dimers twist together to form a 4 molecule protofibril. ▪ Eight protofibrils combine to make one microfibril. ▪ Hundreds of microfibrils are cemented into a macrofibril. keratins Structure α- α-helix (1), Coiled coil ‘dimers’ (2), Protofibril (4), Microfibril (28-32) (7-8 proto), Macrofibril (1000s) (100s micro) * 1000 α-helix Keratin in nails ▪ α-keratin can be hardened by the introduction of disulfide cross-links (fingernails) 11 Having a hair design? -hair style can be changed using cold water and hot water(easier) affecting H-bonds ▪ Temporary Wave ▪ When hair gets wet, water molecules disrupt some of the hydrogen bonds, which help to keep the alpha-helices aligned. When hair dries up, the hair strands are able to maintain the new curl in the hair for a short time. ▪ Permanent wave ▪ A reducing substance (usually ammonium thioglycolate) is added to reduce some of the disulfide cross-links. The hair is put on rollers or curlers to shift positions of alpha- helices. An oxidizing agent, usually hydrogen peroxide, is added to reform the disulfide bonds in the new positions until the hair grows out *keratin is used to straighten hair and has a bad smell & acts as a reducing agent of disulfide bond then an oxidizing agent is used to provide a long-lasting effect ‫تمت كتابة هذا الشيت عن روح والدة زميلنا عمرو رائد من دفعة تيجان‬ ‫دعواتكم لها بالرحمة والمغفرة‬ Thank you 12