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Impact of EU Social Challenges on Biotechnology Education at Pécs and Debrecen Universities

Explore the integration of novel social challenges faced by the European Union into the teaching curriculum of Medical Biotechnology Master’s Programmes at the University of Pécs and the University of Debrecen. This study, identified as TÁMOP-4.1.2-08/1/A-2009-0011, delves into the transformation of educational materials, focusing on G-protein-linked receptors, signal transduction pathways, GPCR structure, and biochemical processes like catecholamine hormone synthesis. By analyzing the impact of EU challenges on biotechnology education, this project aims to enhance the relevance and quality of training in medical biotechnology for aspiring professionals in Europe.

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Impact of EU Social Challenges on Biotechnology Education at Pécs and Debrecen Universities

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  1. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat theUniversity of Pécs and at the University of Debrecen Identificationnumber: TÁMOP-4.1.2-08/1/A-2009-0011

  2. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat theUniversity of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011 Tímea Berki and Ferenc Boldizsár Signaltransduction G-protein-linkedreceptors

  3. Nomenclature • G-protein-coupled receptors (GPCRs) • Seven-transmembrane domain receptors • 7-TM receptors • Heptahelical receptors • Serpentine receptor • G protein-linked receptors (GPLR)

  4. 7-transmembrane-spanning receptors(7-TM) N N-Glycosylation (Receptor folding, trafficking) Ligand-binding GαC-terminaltail EL1 EL2 EL3 Extracellularloops (EL1-3) Gα -binding Other Gαsurfaces Helix 8 (Gβ-binding) Plasmamembrane Interactionsurface TM 1 TM 2 TM 3 TM 4 TM 4 TM 5 TM 6 TM 7 Transmembranehelix (TM1-7) PKC phosphorylation (Desensitization) Intracellularloops (IL1-3) IL1 IL2 IL3 Palmitoylation (Lipid raft localization) E/DRY Motif (Receptor activity and protein-protein interactions) GRK phosphorylation (Desensitization) PKC phosphorylation (Desensitization) C

  5. GPCR

  6. Structure of 7-TM receptors N EL 3 Agonist N EL2 EL1 Intracellularloops TM 7 TM 5 TM 6 InactiveGPCR Active GPCR TM 1 TM 6 TM 7 TM 5 Sideperspective TM 1 TM 3 TM 2 C TM 4 Helix8 TM 3 TM 2 C TM 4 Helix8 Gα IL3 Extracellularloops Ga IL 1 IL2 C-terminal tail of Ga C N EL3 Helix8 TM 6 TM 7 TM 7 IL3 TM 6 TM 1 TM 1 TM 5 TM 5 EL2 TM 3 TM 3 IL1 Intracellularpersective Ga TM 2 TM 2 TM 4 TM 4 EL1 Non-covalent bond IL2 C N Helix8 EL3 IL3 Ga-binding surface IL1 EL2 EL1 IL2

  7. GPCR subtypes • Class A (or 1) – Rhodopsin-like • Class B (or 2) – Secretin receptor family • Class C (or 3) – Metabotropic glutamate/pheromone • Class D (or 4) – Fungal mating pheromone receptors • Class E (or 5) – Cyclic AMP receptors • Class F (or 6) – Frizzeled/Smoothened

  8. Activation of G-protein-coupled receptors (GPCR) Signal molecule G-protein coupled receptor (GPCR) g g g a a a b b b GDP GDP GTP Inactive G-protein g b GDP GTP Plasma membrane g b Cytoplasm a a GTP GTP Activated G-protein subunits

  9. G-proteins G-protein coupled receptor (GPCR) Plasmamembrane Cytoplasm g a b GDP a GTP g b Ion channels PI3K Phospholipases Adenylylcyclases Receptor kinases G12/13 Gi Gs Gq GTP GTP GTP GTP Adenylyl cyclase Adenylyl cyclase PLC PIP2 DAG Activates Rho ATP cAMP ATP cAMP IP3 Phospholipases Ion channels Ca2+

  10. G-protein heterotrimer

  11. Catecholamine hormon synthesis +H3N +H3N CO2– +H3N CO2– OH OH DOPA Tyrosine hydroxylase decarboxylase OH OH OH Dihydroxyphenilalanine(L-DOPA) Tyrosine Dopamine H2+ +H3N N H3C OH OH Phenethanolamine Dopamine HO HO N-methyltransferase β-hydroxylase OH OH Dopamine Epinephrine

  12. Epinephrine and analogues OH OH H H OH NH2 HO N N H CH3 CH3 N .HCL .HCL .H2SO4 CH3 CH3 HO HO CH3 Pseudoephedrine HCL Tyramine HCL 2 Epinephrine (adrenaline) Ephedrine sulphate OH NH2 NH2 NH2 .H2SO4 .H2SO4 .H2SO4 CH3 CH3 2 2 2 Dexamfetamine sulfate Amfetamine sulfate Phenylethanolamine sulfate OH H HO CH3 N OH OH H H .H2SO4 HO CH3 N CH3 N CH3 .H2SO4 HO .HCL CH3 CH3 CH3 OH HO HO 2 2 Isoprenaline HCL Orciprenaline sulfate Salbutamol sulfate OH H HO CH3 N CH3 .H2SO4 CH3 OH 2 Terbutaline sulfate

  13. cAMP-PKA pathway Gα gated channel cAMP gated channel PO4 gated channel Receptor Adenylyl cyclase C C R R P cAMP C C R R P ATP cAMP g a ADP b cAMP cAMP R C cAMP cAMP ATP GTP a a cAMP cAMP R C CREB cAMP cAMP GTP GTP P Activated PKA CREB Inactive PKA P Gene expression CREB CRE Nucleus cAMP Response Element

  14. Primary Action of Epinephrinein a LiverCell Acetylcholine Epinephrine Stress signal Fuel for „fight or flight” Receptor P P P P P Glucose GlucogenSynthase AdenylateCyclase Glucose-6-Phosphatase g ATP cAMP as Glucose-6-P Glucose-1-P Glycogen b Fructose-2,6- bisphosphatase GDP Fructose-1,6- bisphosphatase PFK-1 Glucogen Phosphorylase Fructose-2,6-bisP Fructose-6-P Phosphorylase Kinase A Fructose-1,6-bisP Protein Kinase A PEP PyrKinase Pyruvate

  15. Glucagonsignaling Glucose low in blood PANCREAS Glucagon (Epinephrine) Receptor P P P P Glucose GlycogenSynthase AdenylateCyclase Glucose-6-Phosphatase g ATP cAMP as Glucose-6-P Glucose-1-P Glycogen b Fructose-2,6- bisphosphatase GDP Fructose-1,6- bisphosphatase PFK-1 Glycogen Phosphorylase Fructose-2,6-bisP Fructose-6-P Fructose-1,6-bisP Protein Kinase A PEP PyrKinase Pyruvate

  16. Serotonin receptor • Serotonin receptor → G-protein →adenylylcyclase→ ATP →cAMP→ PKA →cAMPResponseElement (CRE) →Geneexpression

  17. Types of serotonin receptor

  18. Receptor desensitization Desensitized receptor Activated receptor Arrestin ATP ADP GRK G-protein linked receptor kinase P P P P P P

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