Introduction to the biological pathway

1. Introduction to the biological pathway 2003.02.07 POSTECH NLP lab 발표자: 정설경

2. Contents • Introduction • Cell • Biological pathway • Metabolic pathway • Regulatory pathway • Signal transduction pathway • GPCR pathway • Limitation & approach Introduction to the biological pathway

3. Introduction – Cell (1) • Cell 의 종류 • Prokaryote • Eukaryote • Plant cell • Animal cell Introduction to the biological pathway

4. Introduction – Cell (2) • Cell structure • Membrane structure • Plasma membrane • Nuclear membrane • Cell activity • Physiological activity • Chemical activity • Main component: protein Introduction to the biological pathway

5. 인지질의 구조 ( phospholipid ) 막 구조 ( plasma membrane) Introduction to the biological pathway

6. Introduction to the biological pathway

7. Introduction – Cell (2) • Cell structure • Membrane structure • Plasma membrane • Nuclear membrane • Cell activity • Physiological activity • Chemical activity • Main component: protein Introduction to the biological pathway

8. Protein structure (1) Introduction to the biological pathway

9. Protein structure (2) Introduction to the biological pathway

10. Ex> Membrane protein Introduction to the biological pathway

11. Biological pathway • Pathway • 사전적: 좁은 길, 오솔길, 진로(course) • 생화학: 경로 • Biological pathway • Molecular interaction network in biological processes • Metabolic pathway, Regulatory pathway • Number of Pathway • 9644 pathways (PATHWAY database) • 160 pathways involving 744 reactions and 791 substrates (mouse) Introduction to the biological pathway

12. Metabolic pathway • Carbohydrate Metabolism • Glycolysis/Gluconeogenesis • TCA cycle (Citrate cycle) • Energy Metabolism • ATP synthesis • Lipid Metabolism • Nucleotide Metabolism • purine, pyrimidine metabolism • Amino Acid Metabolism • Biodegradation of Xenobiotics Introduction to the biological pathway

13. Introduction to the biological pathway

14. Regulatory pathway • Genetic information processing • Transcription, Translation, Sorting and Degradation. Replication and Repair • Environmental information processing • Membrane transport, Signal transduction, Ligand receptor interaction • Cellular processes • Cell motility, Cell growth and death, Cell communication, Development, Behavior Introduction to the biological pathway

15. Signal transduction pathway • Category of signaling protein • Signal molecule • Receptor • Intracellular signaling protein • Target protein • 4 types of intercellular signaling • Endocrine • Paracrine • Neuronal signaling • Contact-dependent signaling Introduction to the biological pathway

16. Modulation by other molecule Divergence to multiple target Amplification Introduction to the biological pathway

17. Introduction to the biological pathway

18. Signal transduction pathway • 4 types of intercellular signaling • Endocrine • Broad effect, specific receptor • hormones • Paracrine • Within local tissue, enzyme/extracellular matrix • Neuronal signaling • Synapse of neuron, speedy • Contact-dependent signaling • Killer T cell (immune system) Introduction to the biological pathway

19. Signal receptor • Cell surface receptors • On-Off signaling • Ion-channel linked • G-protein linked • Enzyme linked • Intracellular receptors • Steroid, Thyroid hormone • Retinol, Vitamin D Introduction to the biological pathway

20. Introduction to the biological pathway

21. G-protein linked receptors • Structure of receptors • N-terminal : extracellular region • Seven-span transmembrane domain • C-terminal : intracellular signal transduction region • Desensitization of receptors • Phospholylation • PKA, PKC or a member of G-protein-linked receptor kinases(GRKs) family • Receptor inactivation • Receptor sequestration • Receptor down-regulation Introduction to the biological pathway

22. G-protein (1) • α,β,γ subunit • α subunit: complex with GDP • Major family Introduction to the biological pathway

23. G-protein (2) • Mechanism of G-protein • Activation • Dissociation of α-GDP, βγ complex • α-GTP, βγ complex  target protein • Deactivation • G-protein itself: GTPase  association of α-GDP, βγ complex • Target of activated G-protein • Direct – ion channel … • Indirect – second messenger • Adenylate cylase  cAMP • Phospholipase C (PLC)  diacylglycerol(DAG) & inositol 1,4,5-triphosphate(IP3) Introduction to the biological pathway

24. Pathway of indirect signaling • Pathway of cAMP • cAMP  protein kinase A  cell response • Pathway of PLC • DAG  protein kinase C • IP3  Ca2+ ↑ Introduction to the biological pathway

25. cAMP pathway Introduction to the biological pathway

26. PLC pathway (1) Introduction to the biological pathway

27. PLC pathway (2) • Ca2+ signaling • Regulate 70% of protein kinase • Regulated by Calcium binding protein, calmodulin(CAM) • Ca2+ Ca2+-CaM complex  CaM-kinase Introduction to the biological pathway

28. example • Smell receptor • Vision receptor Introduction to the biological pathway

29. Limitation • Cannot effectively • Evaluate them for internal consistency • Evaluate them with consistency for new data : microarrays • Refine them with respect to new data • Integrate them to produce system understanding • They are too large and complex • The printed word cannot be manipulated effectively Introduction to the biological pathway

30. Solution: biological knowledge bases • Store biological knowledge and theories in computers in a declarative form • Amenable to computational analysis and generative user interfaces • Accepted to store data in computers, but not knowledge • Refined, interpreted, consensus views • Establish ongoing efforts to curate (maintain, refine, embellish) these knowledge bases • Such knowledge bases are an integral part of the scientific enterprise Introduction to the biological pathway

31. Pathway/Genome Database pathway reactions compounds proteins operons, promotors, DNA binding site Genes Chromosomes, plasmid CELL Introduction to the biological pathway