生物化学教学课件：Hormones

1、Hormones Tissue-Specific Metabolism: The Division of LaborEvery process in organism is regulated by one or more hormones.hormonal signals integrate and coordinate the metabolic activities of different tissues.The coordination of hormonal signals in mammals is achieved by the neuroendocrine system. 1

2、. Hormones outline1.1 Definition- Hormones are chemical messengers secreted by certain tissues into the blood or interstitial fluid细胞间液, serving to regulate the activity of other cells or tissues.1.2 Chemical property of hormones in vertebrate metabolism(1) peptides or polypeptides, such as insulin

3、or glucagon(2) amino acid derivatives, including the catecholamines 儿茶酚胺 and thyroxine甲状腺素(3) steroid, including glucocorticoids糖皮质激素 and the sex hormones(4)脂肪酸衍生物激素PG(前列腺素）1.3 secretion of hormones Hormone is secreted by endocrine glandEndocrine gland: a group of cells and blood vesselspineal松果体, p

4、ituitary垂体, thyroid甲状腺, parathyroid甲状旁腺, pancreas胰岛, adrenals肾上腺, gonad性腺, thymus胸腺The Endocrine System-a collection of glands that secrete hormonesExample: The secretion of insulinGlucose regulation of insulin secretion by pancreatic cells.Classification of Animal Hormones旁分泌激素内分泌激素1.4 Characters o

5、f hormone action2. Mechanisms of Hormone ActionHormones- active at exceedingly low concentrations. 血液肽类激素的浓度为10-1210-10mol/L，固醇类激素的浓度为10-1010-8mol/LHOW?-depend on signal transduction pathwayHydrophilic Hormones(peptide or AA derivatives)-membrane receptorsHydrophobic Hormones(steroids, FA derivative

6、s)- intracellular receptorsSignal transduction through membrane receptors: Information from outside the cell is conveyed into the cell. A first messenger (hormone), binds to a cell surface receptor. The binding stimulates production of a second messenger inside the cell. The second messenger stimula

7、te reactions of downstream kinase cascade.激素与膜受体结合引发信号转导的5种方式：Hormone receptor charactersMacromolecular receptorThe activity of its functional site is altered by hormone bindingHormones bind tightly to its receptor, dissociation constants ：0.1 M 1.0 pM. The receptor density on a cell surface decide

8、its response to hormone. 2.1 seven-helix receptors activate adenylate cyclasecAMP-Protein Kinase pathwayepinephrine2.1.1 seven-helix receptors most nitrogen hormoneReceptor structure：Middle: 7 helixG ProteinCoupled Receptor(GPCR)2.1.2 G proteins named based on their ability to bind guanine nucleotid

9、es. G proteins are membrane proteins inactive state : binding GDP ,inhibit adenylate cyclase, Gi active state : binding GTP , stimulation of adenylate cyclase ,GsGEF: GDP-GTP Exchange FactorGAP: GTP-hydrolysis Activating Protein2.1.3 cAMP- Second messengersActivation of adenylate cyclase by epinephr

10、ine肾上腺素 or glucagon胰高血糖素 produces cAMPSecond messengers: transmit the hormonal message to the target metabolic pathway. cAMP -second messenger2.1.4 cAMP-Dependent Protein Kinase (PKA)1. cAMP promotes the dissociation of cAMP-dependent protein kinase (R2C2) to give free catalytic monomers (C).2. Subu

11、nit C is the protein kinase, which phosphorylates other proteins.Activation of cAMP-dependent protein kinase, PKA.2.1.5 PKA activates downstream Kinase CascadeExample:Glycogen metabolism is regulated by phosphorylation (dephosphorylation) of a set of proteins in a cascading mechanismEpinephrine acti

12、vating Glycogen metabolism in a cascade mannerCascade Amplification Hormones using cAMP as a second messenger:Calcitonin降血钙素(一种调节血中含钙量之荷尔蒙)Chorionic gonadotroptin绒毛膜促性腺激素corticotropin 促肾上腺皮质激素epinephrine肾上腺素adrenalinefollicle stimulating hormoneglucagons胰高血糖素lipotropin促脂素vasopressin抗利尿激素parathyroid

13、hormone副甲状腺素2.2 Signal transduction pathways involving phosphoinositide 磷酸肌醇 turnover2.2.1 procedure:a. Hormone binds to a receptor.b. stimulates a G protein to bind GTP.c. activates phospholipase C 磷脂酶Cd. IP3 stimulates the release of calcium from its intracellular stores in the endoplasmic reticul

14、um.e. DAG stimulates membrane-bound protein kinase C. protein kinase C requires calcium ion f. Protein kinase C phosphorylates specific serine and threonine residues in target proteins.2.3 Receptors with tyrosine kinase1. Epidermal growth factor (EGF表皮生长因子);2. Platelet-derived growth factor (PDGF血小板

15、生长因子) ;3. Colony-stimulating factor 1 (CSF-1);4. Fibroblast growth factor (FGF 纤维原细胞血小板生长因子);5. InsulinReceptors with Tyrosine Kinase Activity Contain an intrinsic enzymatic activity Phosphorylates tyrosine residue in downstream protein a single membrane-spanning domain. no second messengersInsulin

16、pathwayInsulin receptor:a glycoprotein with an 22 tetrameric structure chain to bindinsulin.chain,C-terminus inthe cell has a protein tyrosine kinaseactivity The kinase activity is essential to the biological activity of the insulin receptorsome cases of non-insulin-dependent diabetes are associated

17、 with receptor mutations that abolish the kinase activity.2.4 Steroid and Thyroid 甲状腺Hormones-Intracellular ReceptorsSteroids and related hormones (i.e., thyroid, vitamin D, and retinoic acid hormones) Act within the nucleusregulate transcription of specific genes (usually positively). Steps:Steroid

18、 hormones transport directly from outside into cytoplasm, then into nucleusbind to specific receptor proteins in the nucleus or cytoplasmreceptor-hormone complexes interact with specific DNA sequences-hormone responsive elements (HREs).regulate transcription of specific genes. Steroid Hormonesrecept

19、ors contain bound zinc and conserved cysteine residues essential for DNA binding.-zinc finger structural motifEffects occurring via membrane receptors: short duration-represent responses to rapid and urgent physiological demands and involve activation or inhibition of preexisting enzymes.Effects of steroids: longer-term changes3. Hormonal Regulation and Integration of Mammalian MetabolismThe major endocrine systems and their target tissuesHormone Release Is Regulated by a Hierarchy of Neur