Chemical Messengers (L16 & 17) PDF

Chemical Messengers transmitter nuoro 1 Done By Fatma Altubaikh...

Chemical Messengers transmitter nuoro 1 Done By Fatma Altubaikh !‫ با‬$‫ قوة ا‬$‫ حول و‬$ ، ! ‫ الحمد‬، !‫ما شاء ا‬ ‫بسم ا! الرحمن الرحيم‬ Cell Signalling cellsigniling In multicellular organisms, there is a need for cells to communicate with one another in order to coordinate their growth and metabolism. as The principal way by which cells communicate with each other is by means of extracellular signalling molecules or hormones. to mm The signalling molecules or hormones are synthesized and secreted by cells that produce a specific response in target cells that have receptors for that signalling molecule. IT'S Ptes Different target cells can respond differently to the same signalling molecule where their responses depend on the itype of receptor and f the2intracellular reaction initiated by that signalling molecules. 2  Cell Signalling man Based on the distance over which the signalling molecule act, Cell signalling can be classified into: Hormonsmovetosestematic cercellation glands 1.Endocrine signalling in which the signalling molecule or hormone such as insulin acts on target cell distant from the site of synthesis in cells of an endocrine organ which is pancreas in the present example. The endocrine cells secret the signalling molecule into the blood stream (or sap in plants) which carries it to the target elsewhere in organism’s body. Insulin rectptor o v 3 0 0 00 Cell Signalling Ex prostaglandin 2. Paracrine signalling in which the signalling molecule effects only target cells close to the cell from which it was secreted. The communication from one nerve cell to another by chemical neurotransmitter is an example of paracrine signalling. 3. Autocrine signalling where a cell responds to a molecule that it has produced itself. 4 cens  0 molecules Signalling molecules Based on the solubility, the signalling molecules are classified into: singleas 1. Amino Acid derivatives which are small molecules structurally related to nonpolar polarand tryptophan an amino acid such as tyrosine derivatives. 1 1 polar 1 1no 1 AA i tyrosine Melatonin tryptophan 2 3 Include hormones and neurotransmitters. 5 Signalling molecules 2. Peptide hormones that consist of chains of amino acids such as glycoproteins and the polypeptide chains (hydrophilic).solubleADH Antidiuretic Hormone, ACTH Adrenocorticotropic givesignaltoreleasehormone Hormone, MSH I Melanocyte Stimulating Hormone. Protien a suger a Hand master G G G g 1 6  Signalling molecules Excholestrol 3. Lipid derivatives )lipophilic) including steroidal hormones and eicosanoids. I 7 Signalling molecules inside Based on their receptors, signalling molecules either bind to 1intracellular cytosol 2 surface receptors. receptors or cell- Except m musestined 1. Apart o from prostaglandins, lipophilic signalling molecules diffuse across the plasma membrane and interact with the intracellular receptors in the cytosol or nucleus where the resulting hormone-receptor complex often binds to regions of the DNA and affect the transcription a of certain DNAmRNA genes. Examples are Steroid hormones defuse And thyroxine. Bind It p.de north it affecting transcriptions 8 signalling lipophilic PG diffuse extraprom  Signalling molecules Or 2. The lipophilic prostaglandins (paracrine signalling molecules) on the other hand bind to cell-surface receptors. EXCEPTION 3. All hydrophilic signalling molecules (including those of or tyrosine derivatives) which cannot diffuse across the hydrophobic interior on the lipid bilayer bind to plasma membrane receptors. 9 Hormones 4 n.mx G Master gland ofccells maturation Endocrine system 10 Pituitary is the Master Gland Cortisol 11 whicharethe twohormonesthatarereleased 1to idinalincorteison 01 bytheactionofsympatheticnervoussystemdirectlyfromHypothalams Hypothalamic regulation of endocrine system AntiDiuretic Hormone or vasopressin Or Neurohypophysis Or Trophic hormones 12 Figure 18.5  Hypothalamus Thyrotropin- Thyroid-stimulating releasing hormone hormone corticotropin Adrenocorticotropic Hormone follicle-stimulating hormone gonadotropin r h Luteinizing Hormone 13 How do hormones regulate cellular activity ? 14  whenCat Example; Ca+ homeostasis Result final Math O normal osteoblastBuild TBth case start cases start 6 preaks milding final sit.D ycat normal 15 Cell-Surface receptors o Cell-surface receptors. o Hydrophilic and some lipophilic signaling molecules (prostaglandins) bind to attached firmly These receptors are integral membrane proteins situated in the plasma membrane that bind the signaling molecule (ligand) with high affinity. specific The ligand binds to a specific site on the receptor like the binding of a substrate to an enzyme. 16 Cell-Surface receptors Binding of the ligand to the receptor causes a conformational change in the It known as signal receptor that initiates a sequence of reactions in the target cell transduction which in turn leads to a change in cellular function. sertis ofreaction ampleficatifect th Efface 17 Cell-Surface receptors The distribution of receptors varies on different cells where there are more than one type of receptor for a particular ligand. This allows different target cells to respond differently to the same signaling molecule or ligand. fetoareceptors Cell-surface receptors are classified into three classes depending on how they transfer the information from the ligand to the interior of the cell: 1. enzyme-linked 2. Ion channel-linked 3. G protein-linked Torsin Kagnate ligand 18  Cell-Surface receptors 1. Enzyme-linked receptor On binding of the ligand, the cell-surface receptor undergoes conformational change that activates an intrinsic enzyme activity. For example, the insulin receptor is a complex of two α subunits and two β subunits held together by disulphide linkages. By binding to the polypeptide insulin, the receptor undergoes a conformational change leading to autophosphorylation of the cytosolic enzymatic domain of the6β subunits where the OH groups of the tyrosine residues are phosphorylated by ATP as the phosphate donor, a receptor tyrosine kinases. adationofphosphate The phosphorylated receptor is then recognized by other proteins which in turnbow modulate various intracellular events. This allows the cell to respond to the hormone properly. In addition, the β subunits can directly phosphorylate target proteins within the cell. 19 Cell-Surface receptors 2. ion-channel receptor Neroussystem paracraim Here binding of the ligand again causes a conformational change which opens the ion-channel receptor. This allows the flow of certain ion through the channel which subsequently alters the electrical potential across the membrane. For example; At the nerve-muscle junction, the neurotransmitter acetylcholine binds to a specific receptors that allow Na+ ions to flow into the target cell and K+ ions out of the target cell. 20 receptor muscells ok in eat out Cell-Surface receptors 1. G protein-linked receptors On binding to its ligand, a G protein-linked receptor activates G protein [guanyl nucleotide (GTP)-binding proteins] which in turn1activate or inhibit either an enzyme the 2 atgenerates a specific second messenger or an ion channel causing a change in the membrane potential. Epinephrine act through interaction with G protein-linked receptor. Enzyme Fctive Inactive needed 2 massenger 21 activats Cell-Surface receptors 1. G protein-linked receptors G proteins are localized on the cytosolic face of the plasma membrane and act as on-off molecular switches. When it has guanosine diphosphate GDP bound, the G protein is in the “off” molecular switches, where the activated receptor causes the G protein to release the GDP and exchange it with GTP. This in turn convert G protein to the “on” state. The activated G protein with its bound GTP then dissociates from the receptor and binds to and activates an effector enzyme (such as adenylate cyclase) which in turn catalyses the formation of a second messenger (such as cAMP). The G protein then hydrolyses the bound GTP to GDP and revert back of its “off” state. 22  23 Second Messengers The binding of signalling molecules (ligands) to guanyl nucleotide (GTP)- binding proteins (G protein-linked receptors) lead to a short-lived increase in the concentration of certain intracellular signalling molecules called second messengers. The second messengers include: 1. 3’, 5’-cyclic AMP (cAMP), 2. 3’, 5’- cyclic GMP (cGMP), 3. inositol 1,4,5-triphosphate (IP3), i 4. 1,2-diacylglycerol s (DAG) 5. and Ca2+ 24  Second Messengers I The elevation in the level of one of these second messengers leads to a rapid alteration in cellular function. cAMP and cGMP are derived from ATP and GTP by the action of CAMP CGMP adenylate cyclase and guanylate cyclase ATP GTP respectively. For example, the action of glucagon is mediated through the cAMP. ATP 25 Second Messengers IP3 and DAG are derived from the membrane lipid action a Omni split phosphatidylinositol 4,5 biphosphate by the action of phospholipase offC which also located in plasma membrane and also activated like adenylate cyclase by G proteins. 26  Second Messengers One of the main actions of the polar IP3 is to diffuse through the cytosol and interact with Ca2+ channels in the ER membrane causing the release of stored Ca2+ ions which in turn mediate various cellular responses. to PIP2; phosphatidylinositol 4,5 biphosphate. DAG; GDP Diacylglycerol. I protein set 27 C PSP phospholipase Second Messengers The DAG (and IP3) which is produced by the hydrolysis of phosphatidylinositol 4,5-Bisphosphate together with Ca2+ ions released from the ER activates protein Kinase C, a membrane-bound enzyme that phosphorylates various target Proteins similarly lead to alterations in a variety of cellular processes. DAG cat I p ER 28 29 30 Neurotransmitters Chemical substances which are released at the end of a nerve fibre by the arrival of a nerve impulse and, by diffusing across the synapse or junction, effects the transfer of the impulse to another nerve fibre, a muscle fibre, or some other structure. Thus, neurotransmitters are required for the communication between nerve cells (neurones) or nerve and muscle cells by a rapid action (within seconds– action then terminated) where their actions could be excitatory or inhibitory 31 Neurotransmitters Numerous neurotransmitters were identified including: AA 1. Small molecule neurotransmitter; the amino acid neurotransmitters 1glutamate,2GABA (γ-aminobutyric acid), and 3glycine. All of these are amino acids, though GABA is not an amino acid that's found in proteins. 2. The biogenic amines (with one or more amine group) which are made from amino acid precursors. Hormones Decarboxylation of histidine 2 32 transmitter Nuoro d Precursor is L-tryptophan Neurotransmitters NitrogenicBase Purin 3. The purinergic neurotransmitters ATP and adenosine, which are nucleotides and nucleosides. tribose Adnan Ach 4. Acetylcholine, which does not fit into any of the other structural categories but is a key neurotransmitter at neuromuscular junctions (where nerves connect to muscles), as well as certain other synapses. 33 Neurotransmitters GAMAglazing glutamatGABA 5. Neuropeptides, The neuropeptides are each made up of three or more amino acids and are larger than the small molecule transmitters. There are a great many different neuropeptides. Some of them include the endorphins As which inhibit pain; Substance P, which AAand enkephalins, carries pain signals; and Neuropeptide Y, which stimulates eating and may act to prevent seizures. 34 Other signalling molecules 1. Retinoic Acid which is derived from vitamin A. 2. Vitamin D which is synthesized in the skin in response to sunlight. 3. NO which is a colourless gas that is relatively stable free radical synthesised from molecular oxygen and guanidinium nitrogen of arginine in the reaction catalysed by NO synthase in many tissues. NO acts near the point of release, entering the targe cell and activating the cytosolic enzyme guanylyl cyclase which catalyses the formation of the cGMP. NO is an essential molecule involved in several physiological and pathological processes within the mammalian body. 4. Cytokines which are a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the 35 immune system and have an effect on other cells.