The circle and the basics of signal transduction. Course Outline. Topic #! Topic lecture! Silverthorn! Membranes (pre-requisite material)" "
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1 Homeostasis 03 The goal of this lecture is to discuss the concept of homeostasis and to introduce basic signal transduction mechanisms involved in homeostatic regulation The sections for this lecture are: Basic concept the circle Homeostasis and the circle ignal transduction Life is a series of chemical reactions occurring in compartmentalized environments. The main purpose of life is to keep itself alive Physiology, the study of how life works, is based on the simultaneous occurrence of the following three concepts: levels of organization structure / function relationship homeostatic regulation The circle and the basics of signal transduction Course Outline Topic # Topic lecture ilverthorn Week 1 to week 2" Topic #1" Topic #2" Introduction (pre-requisite material)" Membranes (pre-requisite material)" " 1-5" 1-5" Pre-requisite" Material" (chapter # 5)" " Topic #3" Homeostasis and ignal Transduction" 6" " lectures, Topic #4" ndocrine Communication and the ndocrine ystem" 7" recitations, Topic #5" Neural Communication and the ensory ystem" 8-11" office hours, review, Topic #6" Muscle, Muscle Contraction and their Regulation" 12-13" exam1 " (chapter # 8)" RVIW #1 material from topic #01 #06 XAM #1 material from topic #01 #06 (33%) Week 3 to week 4" Topic #7" Topic #8" Basic Physiology of the Cardiovascular ystem" Basic Physiology of the Respiratory ystem" 14-17" 18" lectures, recitations, review, exam2" Topic #9" Basic Physiology of the Renal ystem" 19-20" (chapter # 7) " RVIW #2 material from topic #01 #09 XAM #2 material from topic #01 #09 (33%) Week 5 to week 6" Topic #10" Topic #11" Basic Physiology of the Gastrointestinal ystem" Food Intake, Metabolism, nergy Balance and xercise" 21 " 23-25" lectures, recitations, review, exam3" Topic #12" From exual Differentiation to Adult Reproduction" 26" (chapter # 6)" RVIW #3 material from topic #01 #12 XAM #3 material from topic #01 #12 (33%) 1-26" 1-26" " (all tests are cumulative) 1
2 Homeostasis is the idea behind the circle T = signal transduction T integrator afferent path efferent path T sensor T negative feedback path effector ignal transduction (T) is the transfer of info across a membrane into the main components of the circle Basic Biology Concepts How do we know what we know reductionism, the most successful experimental approach in physiology life as chemical reactions occurring under linear versus non-linear conditions integrative physiology and non-linear conditions functional genomics and proteomics, the future of experimental physiology potential problem: knowing more and more about less and less tructure / function relationship and levels of organization 2
3 Basic Biology Concepts communication at cellular and sub-cellular levels neural communication endocrine communication neuroendocrine communication signal transduction pathways cross-talk among signal transduction pathways channels and enzymes as final effectors homeostasis and the concept of feedback regulation the main purpose of life is to keep itself alive Feedback Regulation A B C life runs against a thermodynamic equilibrium energy is used to generate work to keep life alive the need of potential energy stores due to sporadic input theoretical components of a feedback loop ( refrigerator ) visualization of a classic motor reflex arc as feedback the body thermoregulatory control as example homeostatic processes related to thermoregulation life runs against a thermodynamic equilibrium 3
4 Feedback Regulation ( energy ) A life runs against a thermodynamic equilibrium energy is used to generate work to keep life alive the need of potential energy stores due to sporadic input life runs against a thermodynamic equilibrium Feedback Regulation ( the circle ) B theoretical components of a feedback (e.g. the refrigerator ) variable under control (t F/C) thermostat (set point) t F/C detector (feedback) comparator (integrator) common language error signal (on/off) amplifier and engine the circle feedback detector T M P R A T U R negative feedback loop set - point comparator error signal amplifier engine controlled variable chemical reactions are ultimately controlled by negative feedback mechanisms L C T R I C A L I G N A L 4
5 Feedback Regulation ( homeostasis ) life runs against a the circle thermodynamic equilibrium energy is used to generate work to keep life alive the need of potential energy stores due to sporadic input theoretical components of a feedback loop ( refrigerator ) C visualization of a classic motor reflex arc as feedback the body thermoregulatory control as example homeostatic processes related to thermoregulation chemical reactions are ultimately controlled by negative feedback mechanisms Feedback Regulation ( questions ) the circle Questions to be asked about any Homeostatic Reflex chemical reactions are ultimately controlled by negative feedback mechanisms 5
6 Feedback Regulation ( the circle ) the circle thermoregulation homeostatic processes related to thermoregulation chemical reactions are ultimately controlled by negative feedback mechanisms Feedback Regulation ( the circle ) the circle thermoregulation homeostatic processes related to thermoregulation the thermoregulatory control response 6
7 Feedback Regulation ( the circle ) the circle thermoregulation homeostatic processes related to thermoregulation the thermoregulatory control response Feedback Regulation ( the circle ) the circle thermoregulation homeostatic processes related to thermoregulation -Fb the thermoregulatory control response 7
8 Feedback Regulation ( the circle ) the circle thermoregulation homeostatic processes related to thermoregulation the thermoregulatory control response Feedback Regulation ( the circle ) thermoregulation homeostatic processes related to thermoregulation the circle theoretical components of a feedback (e.g. refrigerator ) feedback detector T M P R A T U R negative feedback loop set - point comparator error signal amplifier engine controlled variable The circle is a didactic representation of an homeostatic control system, the basis of physiology L C T R I C A L I G N A L 8
9 Feedback Regulation ( the circle ) thermoregulation homeostatic processes related to thermoregulation the circle theoretical components of a feedback (e.g. refrigerator ) what is fever? feedback detector T M P R A T U R negative feedback loop set - point comparator error signal amplifier engine controlled variable The circle is a didactic representation of an homeostatic control system, the basis of physiology L C T R I C A L I G N A L Homeostasis ( the circle ) the circle ame Important Generalizations About Homeostatic Control ystems 9
10 Homeostasis ( integrators ) comparator / integration centers in CN M PVN integrators compare what it should be with what it actually is and generate an error signal Homeostasis ( integrators ) comparator / integration centers in CN PVN POA IIIV M integrators compare what it should be with what it actually is and generate an error signal 10
11 Homeostasis ( messengers ) (how components of homeostatic control systems talk to each other) most communication strategies involved a ligand binding to a receptor Homeostasis ( messengers ) (how components of homeostatic control systems talk to each other) most communication strategies involved a ligand binding to a receptor 11
12 Homeostasis ( messengers ) (how components of homeostatic control systems talk to each other) most communication strategies involved a ligand binding to a receptor Homeostasis ( signal transduction ) Glossary of Terms concerning Receptors there are intracellular receptors and receptors located in the plasma membrane 12
13 Homeostasis ( signal transduction ) there are intracellular receptors and receptors located in the plasma membrane This is the most important slide of the whole course 13
14 ignal transduction ( receptors ) Receptor Classification based on their Location and ignal Transduction Pathways there are intracellular receptors and receptors located in the plasma membrane ignal transduction ( receptors ) Receptor Classification based on their Location and ignal Transduction Pathways there are intracellular receptors and receptors located in the plasma membrane 14
15 ignal transduction ( receptors ) signal transduction pathways and surface membrane receptors ignal transduction ( paths ) signal transduction pathways and surface membrane receptors 15
16 ignal transduction ( paths ) signal transduction pathways and surface membrane receptors ignal transduction ( paths ) signal transduction pathways and surface membrane receptors AC GC PLC Ca camp cgmp IP3 DAG Amplifier enzymes 2 nd messengers 16
17 ignal transduction ( paths ) signal transduction pathways and surface membrane receptors amplification cascade ignal transduction ( paths ) signal transduction pathways and surface membrane receptors camp is the most widely distributed 2nd messenger 17
18 ignal transduction ( paths ) the Nobel prize was awarded for the discovery of camp and G proteins through G protein, receptor is linked to either an enzyme or a channel to express the effect of a bound ligand dissociation of GDP and binding of GTP to the alpha subunit is elicited by ligand binding to the receptor camp regulates cell functions by binding to camp - dependent PKA ignal transduction ( paths ) membrane receptors using camp stimulate: Rs / Gs: pi, ACTH, AVP, Ang II, LH, FH, TH, 5HT, glucagon inhibit: Ri / Gi: α 2 adrenergic, muscarinic - Ach agonists, opioids e.g. FH on follicles, Ca channels, CRB e.g. glycogen phosphorylase (+) synthetase (-), hormone sensitive lipase (+) e.g. AVP / V2 / Aq3, cystic fibrosis transmembrane regulator (CFTR, Cl channel) e.g. ANP effects (vasodilatation, diuresis natriuresis) through cgmp production keep cation channels open (natriuresis) concepts of membrane receptors link to integrators, amplifiers and cross-talk membrane receptors acting through 2nd messengers other than camp 18
19 ignal transduction ( paths ) other membrane receptor pathways use PLC instead of AC (camp) ignal transduction ( paths ) other membrane receptor pathways use PLA instead of AC (camp) 19
20 ignal transduction ( paths ) other membrane receptor pathways use tyrosine-kinase instead of AC (camp). ignal transduction ( paths ) kinase Cys rich Cys residues hydrophobic aa N H2 CF NH2 terminal = receptor COOH terminal = enzyme JAK kinases other membrane receptor pathways use tyrosine-kinase instead of AC (camp). arial GF insulin PDGF single - tm domain receptors ANP ICF JAK2 GH, Prl, cytokines COOH 20
21 ignal transduction ( paths ) glutamate NMDA receptor calmodulin + NO inactive Ca ion channel calmodulin + Ca NO active arginine NO citrulline other membrane receptor pathways use gases as neural messengers physiological response GTP cgmp NO - Fe guanylyl cyclase ignal transduction ( summary ) e.g. membrane receptors and effectors 21
22 ignal transduction ( summary ) Reference Table of Important econd Messengers Ca camp cgmp DAG ecosanoids IP3 ignal transduction ( summary ) AVP-R Ca-R Rd-R Per toxin Ch toxin 22
23 ignal transduction ( summary ) signal transduction pathways and intracellular receptors ignal transduction ( summary ) signal transduction pathways and intracellular receptors NH DNA Hormone binding binding region region COOH nuclear receptor structure estrogen progesterone glucocorticoid Thyroid (T3) androgen Vitamin D 23
24 ignal transduction ( summary ) signal transduction pathways and intracellular receptors ignal transduction ( summary ) R signal transduction pathways and intracellular receptors steroids T3 - T4 vitd Na / K pump camp ----> PKA ----> channel / enzyme AC Protein synthesis XX1 HR mrna R DNA 24
25 Homeostasis ( the circle ) the circle Homeostasis ( the circle ) the circle -Fb 25
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