Amylin Receptor Agonists
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Amylin Receptor Agonists
Amylin, or islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone. It is co-secreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1 (insulin:amylin). Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels. IAPP is processed from an 89-residue coding sequence. Proislet amyloid polypeptide (proIAPP, proamylin, proislet protein) is produced in the pancreatic beta cells (β-cells) as a 67 amino acid, 7404 Dalton pro-peptide and undergoes post-translational modifications including protease cleavage to produce amylin. Synthesis ProIAPP consists of 67 amino acids, which follow a 22 amino acid signal peptide which is rapidly cleaved after translation of the 89 amino acid coding sequence. The human sequence (from N-terminus to C-terminus) is: (MGILKLQVFLIVLSVALNHLKA) TPIESHQVEKR^ KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTYG^ KR^ NAVEVLKREPLN ...
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Posttranslational Modification
In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translate mRNA into polypeptide chains, which may then change to form the mature protein product. PTMs are important components in cell signalling, as for example when prohormones are converted to hormones. Post-translational modifications can occur on the amino acid side chains or at the protein's C- or N- termini. They can expand the chemical set of the 22 amino acids by changing an existing functional group or adding a new one such as phosphate. Phosphorylation is highly effective for controlling the enzyme activity and is the most common change after translation. Many eukaryotic and prokaryotic proteins also have carbohydrate molecules attached to them in a process called glycosylation, which can promote protein folding and improve stability a ...
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Insulin Resistance
Insulin resistance (IR) is a pathological response in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood sugar). Insulin is released by the pancreas in response to carbohydrates consumed in the diet. In states of insulin resistance, the same amount of insulin does not have the same effect on glucose transport and blood sugar levels. There are many causes of insulin resistance and the underlying process is still not completely understood. Risk factors for insulin resistance include obesity, sedentary lifestyle, family history of diabetes, various health conditions, and certain medications. Insulin resistance is considered a component of the metabolic syndrome. Insulin resistance can be improved or reversed with lifestyle approaches, such a ...
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Type 2 Diabetes
Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Other symptoms include increased hunger, having a sensation of pins and needles, and sores (wounds) that heal slowly. Symptoms often develop slowly. Long-term complications from high blood sugar include heart disease, stroke, diabetic retinopathy, which can result in blindness, kidney failure, and poor blood flow in the lower limbs, which may lead to amputations. A sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon. Type 2 diabetes primarily occurs as a result of obesity and lack of exercise. Some people are genetically more at risk than others. Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primar ...
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Fatty Acids
In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, from 4 to 28. Fatty acids are a major component of the lipids (up to 70% by weight) in some species such as microalgae but in some other organisms are not found in their standalone form, but instead exist as three main classes of esters: triglycerides, phospholipids, and cholesteryl esters. In any of these forms, fatty acids are both important dietary sources of fuel for animals and important structural components for cells. History The concept of fatty acid (''acide gras'') was introduced in 1813 by Michel Eugène Chevreul, though he initially used some variant terms: ''graisse acide'' and ''acide huileux'' ("acid fat" and "oily acid"). Types of fatty acids Fatty acids are classified in many ways: by length, by saturation vs unsat ...
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Tumor Necrosis Factor Alpha
Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors on other cells. It is a member of the tumor necrosis factor superfamily, a family of transmembrane proteins that are cytokines, chemical messengers of the immune system. Excessive production of TNF plays a critical role in several inflammatory diseases, and TNF-blocking drugs are often employed to treat these diseases. TNF is produced primarily by macrophages but is also produced in several other cell types, such as T cells, B cells, dendritic cells, and mast cells. It is produced rapidly in response to pathogens, cytokines, and environmental stressors. TNF is initially produced as a type II transmembrane protein (tmTNF), which is then cleaved by TNF alpha converting enzyme (TACE) into a soluble form (sTNF) and secreted from the cel ...
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Promoter (biology)
In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription (genetics), transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, Upstream and downstream (DNA), upstream on the DNA (towards the Directionality (molecular biology)#5′-end, 5' region of the sense strand). Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism. Overview For transcription to take place, the enzyme that synthesizes RNA, known as RNA polymerase, must attach to the DNA near a gene. Promoters contain specific DNA sequences such as response elements that provide a secure initial binding site for RNA polymerase and for ...
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Lipotoxicity
Lipotoxicity is a metabolic syndrome that results from the accumulation of lipid intermediates in non-adipose tissue, leading to cellular dysfunction and death. The tissues normally affected include the kidneys, liver, heart and skeletal muscle. Lipotoxicity is believed to have a role in heart failure, obesity, and diabetes, and is estimated to affect approximately 25% of the adult American population. Cause In normal cellular operations, there is a balance between the production of lipids, and their oxidation or transport. In lipotoxic cells, there is an imbalance between the amount of lipids produced and the amount used. Upon entrance of the cell, fatty acids can be converted to different types of lipids for storage. Triacylglycerol consists of three fatty acids bound to a glycerol molecule and is considered the most neutral and harmless type of intracellular lipid storage. Alternatively, fatty acids can be converted to lipid intermediates like diacylglycerol, ceramides and fatt ...
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Amine
In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of electrons. Amines can also exist as hetero cyclic compounds. Aniline is the simplest aromatic amine, consisting of a benzene ring bonded to an amino group. Amines are classified into three types: primary (1°), secondary (2°), and tertiary (3°) amines. Primary amines (1°) contain one alkyl or aryl substituent and have the general formula RNH2. Secondary amines (2°) have two alkyl or aryl groups attached to the nitrogen atom, with the general formula R2NH. Tertiary amines (3°) contain three substituent groups bonded to the nitrogen atom, and are represented by the formula R3N. The functional group present in primary amines is called the amino group. Classification of amines Amines can be classified according to the nature and number o ...
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Peptidylglycine Alpha-amidating Monooxygenase
Peptidyl-glycine alpha-amidating monooxygenase, or PAM, is an enzyme that catalyzes the conversion of an n+1 residue long peptide with a C-terminal glycine into an n-residue peptide with a terminal amide group. In the process, one molecule of is consumed and the glycine residue is removed from the peptide and converted to glyoxylic acid. The enzyme is involved in the biosynthesis of many signaling peptides and some fatty acid amides. In humans, the enzyme is encoded by the '' PAM'' gene. This transformation is achieved by conversion of a prohormone to the corresponding amide (C(=O)NH2). This enzyme is the only known pathway for generating peptide amides. Replacing the carboxylic acid group with an amide group makes the peptide more hydrophobic and more likely to be neutrally charged at physiologic pH, and it is believed that these neutrally charged peptide amides can more easily bind to receptors. Function This gene encodes a multifunctional protein. It has two enzymatical ...
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Glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (GGU, GGC, GGA, GGG). Glycine disrupts the formation of alpha-helices in secondary protein structure. Its small side chain causes it to favor random coils instead. Glycine is also an inhibitory neurotransmitter – interference with its release within the spinal cord (such as during a '' Clostridium tetani'' infection) can cause spastic paralysis due to uninhibited muscle contraction. It is the only achiral proteinogenic amino acid. It can fit into both hydrophilic and hydrophobic environments, due to its minimal side chain of only one hydrogen atom. History and etymology Glycine was discovered in 1820 by French chemist Henri Braconnot when he hydrolyzed gelatin by boiling it with sulfuric acid. He originally called it "sugar of ...
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Arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the amino and guanidino groups are protonated, resulting in a cation. Only the -arginine (symbol Arg or R) enantiomer is found naturally. Arg residues are common components of proteins. It is Genetic code, encoded by the DNA codon table, codons CGU, CGC, CGA, CGG, AGA, and AGG. The guanidine group in arginine is the Precursor (chemistry), precursor for the biosynthesis of nitric oxide. Like all amino acids, it is a white, water-soluble solid. The one-letter symbol R was assigned to arginine for its phonetic similarity. History Arginine was first isolated in 1886 from Lupinus luteus, yellow lupin seedlings by the German chemist Ernst Schulze (chemist), Ernst Schulze and his assistant Ernst Steiger. He named it from the Greek ''árg ...
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