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What Is The Chemical Composition Of Insulin?

Pdb-101: Molecule Of The Month: Insulin

Pdb-101: Molecule Of The Month: Insulin

The hormone insulin helps control the level of glucose in the blood Insulin and proinsulin, with A-chain in green, B-chain in blue and disulfide linkages in yellow. Our cells communicate using a molecular postal system: the blood is the postal service and hormones are the letters. Insulin is one of the most important hormones, carrying messages that describe the amount of sugar that is available from moment to moment in the blood. Insulin is made in the pancreas and added to the blood after meals when sugar levels are high. This signal then spreads throughout the body, binding to insulin receptors on the surface of liver, muscle and fat cells. Insulin tells these organs to take glucose out of the blood and store it, in the form of glycogen or fat. Insulin is a tiny protein. It moves quickly through the blood and is easily captured by receptors on cell surfaces, delivering its message. Small proteins pose a challenge to cells: it is difficult to make a small protein that will fold into a stable structure. Our cells solve this problem by synthesizing a longer protein chain, which folds into the proper structure. Then, the extra piece is clipped away, leaving two small chains in the mature form. These two chains are shown in the lower diagram in blue and green, for insulin from pigs (PDB entry 4ins ). The structure is further stabilized by three disulfide bridges, one of which is seen in yellow in each illustration. When insulin function is impaired, either by damage to the pancreas or by the rigors of aging, glucose levels in the blood rise dangerously, leading to diabetes mellitus. For people totally deficient in insulin, such as children that develop diabetes early in life, this can be acutely dangerous. High glucose levels lead to dehydration, as the body attempts to Continue reading >>

Insulin

Insulin

Insulin, hormone that regulates the level of sugar (glucose) in the blood and that is produced by the beta cells of the islets of Langerhans in the pancreas. Insulin is secreted when the level of blood glucose rises—as after a meal. When the level of blood glucose falls, secretion of insulin stops, and the liver releases glucose into the blood. Insulin was first reported in pancreatic extracts in 1921, having been identified by Canadian scientists Frederick G. Banting and Charles H. Best and by Romanian physiologist Nicolas C. Paulescu, who was working independently and called the substance “pancrein.” After Banting and Best isolated insulin, they began work to obtain a purified extract, which they accomplished with the help of Scottish physiologist J.J.R. Macleod and Canadian chemist James B. Collip. Banting and Macleod shared the 1923 Nobel Prize for Physiology or Medicine for their work. Insulin is a protein composed of two chains, an A chain (with 21 amino acids) and a B chain (with 30 amino acids), which are linked together by sulfur atoms. Insulin is derived from a 74-amino-acid prohormone molecule called proinsulin. Proinsulin is relatively inactive, and under normal conditions only a small amount of it is secreted. In the endoplasmic reticulum of beta cells the proinsulin molecule is cleaved in two places, yielding the A and B chains of insulin and an intervening, biologically inactive C peptide. The A and B chains become linked together by two sulfur-sulfur (disulfide) bonds. Proinsulin, insulin, and C peptide are stored in granules in the beta cells, from which they are released into the capillaries of the islets in response to appropriate stimuli. These capillaries empty into the portal vein, which carries blood from the stomach, intestines, and pancrea Continue reading >>

Structure Of Insulin

Structure Of Insulin

Insulin is composed of two peptide chains referred to as the A chain and B chain. A and B chains are linked together by two disulfide bonds, and an additional disulfide is formed within the A chain. In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids. Although the amino acid sequence of insulin varies among species, certain segments of the molecule are highly conserved, including the positions of the three disulfide bonds, both ends of the A chain and the C-terminal residues of the B chain. These similarities in the amino acid sequence of insulin lead to a three dimensional conformation of insulin that is very similar among species, and insulin from one animal is very likely biologically active in other species. Indeed, pig insulin has been widely used to treat human patients. Insulin molecules have a tendency to form dimers in solution due to hydrogen-bonding between the C-termini of B chains. Additionally, in the presence of zinc ions, insulin dimers associate into hexamers. These interactions have important clinical ramifications. Monomers and dimers readily diffuse into blood, whereas hexamers diffuse poorly. Hence, absorption of insulin preparations containing a high proportion of hexamers is delayed and somewhat slow. This phenomenon, among others, has stimulated development of a number of recombinant insulin analogs. The first of these molecules to be marketed - called insulin lispro - is engineered such that lysine and proline residues on the C-terminal end of the B chain are reversed; this modification does not alter receptor binding, but minimizes the tendency to form dimers and hexamers. Send comments to [email protected] Continue reading >>

The Chemistry And Biochemistry Of Insulin

The Chemistry And Biochemistry Of Insulin

The Chemistry and Biochemistry of Insulin Please review our Terms and Conditions of Use and check box below to share full-text version of article. I have read and accept the Wiley Online Library Terms and Conditions of Use. Use the link below to share a full-text version of this article with your friends and colleagues. Learn more. Get access to the full version of this article. View access options below. You previously purchased this article through ReadCube. View access options below. Purchase options have been disabled temporarily. Please try again later. The protein hormone insulin occurs widely in the animal kingdom. Although its biological function is always the same, its aminoacid composition varies widely. Insulin consists of two polypeptide chains, which are linked by three cystine residues to form a bicyclic system with a 20membered and an 85membered ring. The protein crystallizes in various forms with foreign ions. In solution, insulin normally forms aggregates of 2n molecules. The hormone can be regenerated from the separated polypeptide chains, and its total synthesis has been achieved in a similar manner from synthesized peptide chains. In the biosynthesis of insulin, the two chains are evidently built up separately and subsequently linked together. Insulin promotes the synthesis of glycogen, fat, and protein in the organism; insulin deficiency leads to an increase in the bloodsugar level. At the molecular level, the mechanism of action of the hormone is still unknown. Current hypotheses are discussed. No specific active center has so far been detected in the insulin molecule, which contains several antigenic regions. Continue reading >>

The Chemical Nature Of Insulin.

The Chemical Nature Of Insulin.

SAGE Video Streaming video collections SAGE Knowledge The ultimate social sciences library SAGE Research Methods The ultimate methods library SAGE Stats Data on Demand CQ Library American political resources About Privacy Policy Terms of Use Contact Us Help Health Sciences Life Sciences Materials Science & Engineering Social Sciences & Humanities Journals A-Z Authors Editors Reviewers Librarians Researchers Societies Advertising Reprints Content Sponsorships Permissions ISSN: 1535-3702 Online ISSN: 1535-3699 Continue reading >>

Insulin - An Overview | Sciencedirect Topics

Insulin - An Overview | Sciencedirect Topics

Insulin is a protein consisting of two polypeptide chains, A chain and B chain, linked together by disulfide bonds. Brian L. Furman, in xPharm: The Comprehensive Pharmacology Reference , 2007 Insulin is normally secreted rapidly from the beta-cells of the pancreatic islets in response to nutrients absorbed after a meal. In type 1 diabetes mellitus, there may be an absolute insulin deficiency as a consequence of autoimmune destruction of the beta-cells. On the other hand, in type 2 diabetes mellitus, insulin secretion is impaired and is inadequate to overcome peripheral insulin resistance. Insulin preparations are used to replace the deficient hormone in the treatment of diabetes, and currently, there is no alternative therapy for type 1 diabetes. Insulin is also to be used in the treatment of type 2 diabetes when this cannot be adequately controlled by orally active antidiabetic drugs. The aim of treatment using insulin is to maintain euglycemia (a plasma glucose level of 47 mmol/L) without causing hypoglycemia. There is much evidence that good control in both type 1 and type 2 diabetes will reduce the development of long-term microvascular and neuropathic complications of the disorder DCCT Research Group (1993), UK Prospective Diabetes Study Group (1998). However, good control is difficult to achieve because of the difficulty of administering insulin in a way that mimics physiological insulin secretion, with rapid peaks during and immediately after a meal and low, basal concentrations between meals. Insulin preparations are now largely based on human insulin prepared by enzymic modification of porcine insulin [human insulin (emp)], by chemical combination of the A and B chains produced using bacteria genetically modified by recombinant DNA technology [human insulin (c Continue reading >>

Insulin

Insulin

A protein with an impressive roster of ‘firsts’: Anna Lewcock introduces insulin Meera Senthilingam This week, a first for protein synthesis, resulting in a compound saving the lives of millions worldwide. Anna Lewcock… Anna Lewcock The year is 1922. Fourteen-year-old Leonard Thompson is at death’s door. Weighing just four and half stone, he is admitted to hospital slipping into a coma. In desperation, his father allows doctors to inject Leonard with a new drug never before tested on humans. But his son suffers an allergic reaction, and remains critically ill. Two weeks later, the doctors try again with a purer form of the extract. This time, the results are staggering. Leonard quickly regains his strength, his appetite, and his life. All thanks to a modest molecule called insulin. Insulin is a peptide hormone produced by the pancreas. But in the 371 million people worldwide who suffer from diabetes, something is amiss. In type 1 diabetes, the pancreas doesn’t produce any insulin. In the more common type 2, it doesn’t produce enough or the insulin it does produce doesn’t work properly. Insulin unlocks the body’s cells, allowing glucose in to be used for energy. With the body unable to metabolise glucose, it builds up in the blood leading to dangerously high blood sugar levels, and if left untreated, can lead to devastating health complications. Before the discovery of insulin, it was essentially a death sentence: patients with Type 1 diabetes were put on a starvation diet and given just months to live. Diabetes has been recognised as an illness for thousands of years. But it wasn’t until the late 1800s that researchers suggested we should look to the pancreas for a substance responsible for metabolic control. It then took until the 1920s for it to be i Continue reading >>

The Chemistry Of Insulin Apart

The Chemistry Of Insulin Apart

Introduction Insulin is an amazing drug that is used to help diabetic people live as healthy lives as they can. The drug is injected by syringe after a diabetic person eats, replacing the natural process that occurs in nondiabetic people, where insulin is transferred from the pancreas to the bloodstream into cells to take the new sugar and use it for energy or later use. Novolog, or insulin aspart, a specific type and brand of insulin, works in its own specific way. Insulin aspart is called rapid-acting insulin, in which the composition is manipulated from normal insulin to make it work faster. Insulin aspart starts to work 15 min after it is injected. I chose to do insulin, specifically insulin aspart, because I have been a type 1 diabetic for 8 years and use it everyday. Before researching, I was interested in how close man-made insulin was to human insulin, and it turns out that they are almost identical, being only one amino acid different. Insulin has always fascinated me. Insulin has affected my life in great ways. It is the single reason that I am still alive and healthy. Without it, especially insulin aspart, I do not even want to image what my life would look like, or what could ever take its place. Composition of ... C256H381N65O79S6 100 Units/mL Zinc = 19.6 mcg/mL Disodium hydrogen phosphate dihydrate = 1.25 mg/mL m-Cresol = 1.72 mg/mL Phenol = 1.5 mg/mL Glycerin = 16 mg/mL Sodium Chloride = .58 mg/mL Water = remainder for injection Main Chemicals, Compounds, Components Glycerin = C3H8O3 Glycerin is a simple sugar alcohol compound that is used in insulin as an isotonicity agent, or thing that makes insulin flow inside a body, like water. It is also a humectant, which means that it keeps insulin in liquid form for longer. Glycerin is a very important part of i Continue reading >>

Structure And Composition Of Insulin Fibril Surfaces Probed By Ters

Structure And Composition Of Insulin Fibril Surfaces Probed By Ters

Abstract Amyloid fibrils associated with many neurodegenerative diseases are the most intriguing targets of modern structural biology. Significant knowledge has been accumulated about the morphology and fibril-core structure recently. However, no conventional methods could probe the fibril surface despite its significant role in the biological activity. Tip-enhanced Raman spectroscopy (TERS) offers a unique opportunity to characterize the surface structure of an individual fibril due to a high depth and lateral spatial resolution of the method in the nanometer range. Herein, TERS is utilized for characterizing the secondary structure and amino acid residue composition of the surface of insulin fibrils. It was found that the surface is strongly heterogeneous and consists of clusters with various protein conformations. More than 30% of the fibril surface is dominated by β-sheet secondary structure, further developing Dobson’s model of amyloid fibrils (Jimenez et al. Proc. Natl. Acad. Sci. U.S.A.2002, 99, 9196–9201). The propensity of various amino acids to be on the fibril surface and specific surface secondary structure elements were evaluated. β-sheet areas are rich in cysteine and aromatic amino acids, such as phenylalanine and tyrosine, whereas proline was found only in α-helical and unordered protein clusters. In addition, we showed that carboxyl, amino, and imino groups are nearly equally distributed over β-sheet and α-helix/unordered regions. Overall, this study provides valuable new information about the structure and composition of the insulin fibril surface and demonstrates the power of TERS for fibril characterization. Continue reading >>

How Insulin Is Made - Material, Manufacture, History, Used, Parts, Components, Structure, Steps, Product

How Insulin Is Made - Material, Manufacture, History, Used, Parts, Components, Structure, Steps, Product

Background Insulin is a hormone that regulates the amount of glucose (sugar) in the blood and is required for the body to function normally. Insulin is produced by cells in the pancreas, called the islets of Langerhans. These cells continuously release a small amount of insulin into the body, but they release surges of the hormone in response to a rise in the blood glucose level. Certain cells in the body change the food ingested into energy, or blood glucose, that cells can use. Every time a person eats, the blood glucose rises. Raised blood glucose triggers the cells in the islets of Langerhans to release the necessary amount of insulin. Insulin allows the blood glucose to be transported from the blood into the cells. Cells have an outer wall, called a membrane, that controls what enters and exits the cell. Researchers do not yet know exactly how insulin works, but they do know insulin binds to receptors on the cell's membrane. This activates a set of transport molecules so that glucose and proteins can enter the cell. The cells can then use the glucose as energy to carry out its functions. Once transported into the cell, the blood glucose level is returned to normal within hours. Without insulin, the blood glucose builds up in the blood and the cells are starved of their energy source. Some of the symptoms that may occur include fatigue, constant infections, blurred eye sight, numbness, tingling in the hands or legs, increased thirst, and slowed healing of bruises or cuts. The cells will begin to use fat, the energy source stored for emergencies. When this happens for too long a time the body produces ketones, chemicals produced by the liver. Ketones can poison and kill cells if they build up in the body over an extended period of time. This can lead to serious illne Continue reading >>

The Structure Of A Protein Hormone, Insulin

The Structure Of A Protein Hormone, Insulin

The structure of a protein hormone, insulin Get access/doi/pdf/10.1080/00107517108213714?needAccess=true Hormones are chemical substances involved in the regulation and integration of metabolic processes. For the first time, the three-dimensional structure of a protein hormone, insulin, has been worked out by x-ray crystallographio analysis using isomorphous replacement and anomalous scattering methods. The basic repeating unit in the crystals studied is an insulin hexamer. The three dimers in the hoxamer are related to one another by a crystallographio threefold axis. The two molecules in each dimer are related to each other by a local twofold axis. In the insulin molecule the two polypeptide chains, the A and the B chains, are held together by two disulphide bridges, and hydrophobic and polar side chain interactions. The dimer structure is stabilized by hydrophobic interactions and interchain hydrogen bonds. The stabilization of the hexamer is achieved by predominantly non-polar interactions between adjacent dimers and the co-ordination of the molecules to the two zinc ions on the threefold axis. Finally, the analysis provides some interesting insights into the relationship between the structure and the biological role of insulin. Continue reading >>

Mechanism Of Insulin Chain Combination

Mechanism Of Insulin Chain Combination

ASYMMETRIC ROLES OF A-CHAIN -HELICES IN DISULFIDE PAIRING * 210 The A and B chains of insulin combine to form native disulfide bridges without detectable isomers. The fidelity of chain combination thus recapitulates the folding of proinsulin, a precursor protein in which the two chains are tethered by a disordered connecting peptide. We have recently shown that chain combination is blocked by seemingly conservative substitutions in the C-terminal -helix of the A chain. Such analogs, once formed, nevertheless retain high biological activity. By contrast, we demonstrate here that chain combination is robust to non-conservative substitutions in the N-terminal -helix. Introduction of multiple glycine substitutions into the N-terminal segment of the A chain (residues A1A5) yields analogs that are less stable than native insulin and essentially without biological activity. 1H NMR studies of a representative analog lacking invariant side chains IleA2and ValA3 (A chain sequence GGGEQCCTSICSLYQLENYCN; substitutions are italicized and cysteines are underlined) demonstrate local unfolding of the A1A5 segment in an otherwise native-like structure. That this and related partial folds retain efficient disulfide pairing suggests that the native N-terminal -helix does not participate in the transition state of the reaction. Implications for the hierarchical folding mechanisms of proinsulin and insulin-like growth factors are discussed. Insulin is a globular protein containing two chains, A (21 residues) and B (30 residues). The monomer in solution ( 1 , 2 ) resembles the crystallographic T-state ( 3 ), an -helix-rich structure stabilized by three disulfide bridges (Fig. 1 A). The hormone is generated in vivo by proteolytic processing of a single-chain precursor, proinsulin ( 4 ). Fold Continue reading >>

Insulin

Insulin

This article is about the insulin protein. For uses of insulin in treating diabetes, see insulin (medication). Not to be confused with Inulin. Insulin (from Latin insula, island) is a peptide hormone produced by beta cells of the pancreatic islets, and it is considered to be the main anabolic hormone of the body.[5] It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells.[6] In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both.[6] Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood.[7] Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat. Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited.[8] Their neighboring alpha cells, by taking their cues from the beta cells,[8] secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high.[6][8] Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin.[6][8] The secretion of insulin and glucagon into the Continue reading >>

Insulin, Chemical Structure And Metabolism

Insulin, Chemical Structure And Metabolism

Insulin is a polypeptide hormone formed, after elimination of C peptide by hydrolysis, of two chains of 21 and 30 amino acids, connected by two disulfide bridges. It is secreted by the ß cells of the islets of Langerhans of the pancreas and exerts an hypoglycemic action. It belongs to the group of peptides called IGF (insulin like growth factors) or somatomedins. Biosynthesis Insulin is produced in beta cells which constitute 75% of the islets of Langerhans of the pancreas. Alpha cells secrete glucagon, delta cells somatostatin. Insulin is synthesized in the form of a single polypeptide chain, preproinsulin which is transformed into proinsulin which, itself, catalyzed by proteases called furines, gives insulin and C peptide (C for connecting, because connecting the two chains A and B). Bound to two zinc atoms, insulin is stored in granules as a polymer, probably a hexamer. Secretion Insulin, as well as C peptide, are released by exocytosis into the portal venous system which leads it directly to the liver, which takes up nearly 50%. The remainder of insulin is distributed throughout the body. With a basal secretion of approximately 40 microgram/h under fasting conditions, there are increases of secretion linked to meals. To these slow variations are superimposed peaks of pulsatile secretion. The aim of the treatments by exogenous insulin is to approach the physiological curve of secretion. The principal stimulant of insulin secretion is glucose; it elicits a biphasic release: an immediate effect of short duration and a sustained effect. The cells of the islets are connected by tight junctions, which allow the transfer of ions, of metabolites, secondary messengers from one cell to another, and thus play an important part in synchronizing the secretions. The stimulation Continue reading >>

Insulin Protein Structure

Insulin Protein Structure

The structure of insulin is different among different species of animals. However, essentially it is a protein chain that is similar in many ways among animals. Human insulin is closest in structure and function with cow (bovine) or pig (porcine) insulin. Bovine insulin differs from human in only three amino acid residues, and porcine insulin in one. Insulin from some invertebrates and even fishes can be clinically useful in humans as they possess several similarities. Insulin structure Normal insulin that is biologically active is monomeric or exists as a single molecule. It has two long amino acid chains or polypeptide chains. The chains are chain A with 21 amino acids and chain B with 30 amino acids. Two disulfide bridges (residues A7 to B7, and A20 to B19) covalently connect the chains, and chain A contains an internal disulfide bridge (residues A6 to A11). These joints are similar in all mammalian forms of insulin. When secreted insulin joins in two’s to form dimmers and then in six’s to form hexamers. This combination takes place in the presence of zinc. The peptide chains then form 2 dimensional and three dimensional forms. Each of these 3-dimensional structures have three helices and three conserved disulfide bridges. This is a basic fold. This basic fold is present in all members of the insulin peptide family. At the core or center of the molecules is a hydrophobic or “water-hating” or water repellent area. These cluster of hydrophobic residues in the center contributes to protein stability. Stability is also lent by the disulfide bridges. Surrounding its core, the monomer has two extensive nonpolar surfaces. One of them is a flat one that is aromatic and gets buried when there is a dimer formation. The other surface is more extensive and disappears whe Continue reading >>

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