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  1. Homeostasis
    Maintainence and regulation of a constant internal environment
  2. How homeostasis work?
    Any deviation from the norm will provide a response to nullify the effect and return it back to norm. When conditions are restored to the reference point, the info is feedback to the control centre via the detector, preventing further corrective action. (Negative Feedback)
  3. Principle of Negative Feedback
    Any deviation from the norm will provide a response to nullify the effect and return it back to norm.
  4. Principle of Self Regulation
    System is itself affected by and subjected to the effect it produces
  5. 2 SYSTEMS
    endocrine and nervous system
  6. Hormones are
    chemical messengers
  7. All hormone secreting cells constitutes the
    • endocrine system:
    • endocrine glands - ductless glands as they secret chemical messengers directly into body fluids
  8. Endocrine system
    responsible for communication between cells via release of chemical substances known as hormones
  9. Characteristics of endocrine control
    • Horomes secreted into bloodstream so reach every cell of body
    • BUT hormone act on specific target organs only, only on cells that possess the appropriate receptor molecules on their surfaces
  10. Endocrine Glands
    • Endocrine system consists of widely separated endocrine glands which secrete one or more hormones into the bloodstream directly.
    • They are richly supplied with networks or capillaries that facilitate the release of hormones into the bloodsteam
  11. Amino acids and catecholamines
    • Water soluble molecules
    • Thyroxine - A.A
    • Adrenaline - Catecholamine
    • Stored in membrane bound vesicles within cytoplasm
  12. Proteins
    • Water soluble
    • Insulin
    • Glucagon
    • Stored in membrane bound vesicles within cytoplasm
  13. Steroids
    • are lipids
    • Fat soluble, made from cholesterol.
    • Oestrogen and testosterone
    • Accumulate within cell cytoplasm as lipid droplets
  14. Hormones
    realeased in minute amounts from endocrine glands to bloodstream
  15. Hormones are specific in action
    • Site of their action is determined by the location of the appropriate receptor that interacts with the hormone and ONLY TARGET CELLS have hormone receptors
    • Solubility in water/lipid determines the way in which a hormone acts one cells
  16. Water soluble hormones (protein and catecholamine)
    • i.e Insulin & adrenaline
    • do not enter target cells
    • They bind with receptors on cell surface membrane and sets off a series of events inside the cell (signal transduction pathway)
    • EXCEPTIONAL: a.a hormone thyroxine
  17. Thyroxine and steroid hormones (LIPID SOLUBLE)
    • pass through cell surface membrane, into cell where they bind with receptors in nucleus.
    • Ability to do so because it is protected by a protein (lipoprotein) thus can stay in blood.
    • Hormone receptor complex can bind with DNA, regulating transcription (REGULATION)
  18. Transduction
    • steroid (lipid soluble) hormones form hormone-receptor complex with intracellular receptors
    • This complex initiates the cellular response to the hormone, most often in the form of synthesis of new proteins (as hormone receptor complex can bind with DNA, regulate transcription)
    • Water soluble homrones bind with glycoprotein receptor on cell surface membrane and initiate steps involved in transduction of signal. These steps = activation of enzymes by phosphorylation (add phosphate grp to protein) / use of 2nd messengers
  19. Response
    • Cell membrane -> affects membrane permeability by binding with specific receptor on cell membrane and altering molecule arrangement
    • Cellular organelles -> regulates organelle function
    • Genes -> affects gene expression by binding with specific receptor passes through cell membrane, enter nucleus activates specific genes, leads to synthesis of proteins
  20. Duration of Hormone Action (sidenote)
    • Biological half life of hormones in the blood is very short
    • As after release, they are rapidly inactivated and destroyed by enzymes in liver and target tissues, eliminated through kidneys.
    • HOWEVER, hormones bound to proteins, they are relatively stable with lower rate of breakdown and excretion and longer effective life.
    • Set point : 800mg/dm3 ~ 900mg/dm3
    • Cells require constant supply of glucose(Resp. substrate)
    • Blood glucose drops below 600mg per dm3 hypoglycaemia
    • Blood glucose high is hyperglycaemia
    • High conc. of solute lowers water potential and draw water out of cells
  22. How glucose is added
    • Carbo rich foods are eaten, digested to monosaccharides
    • Hydrolysis of glycogen to glucose
    • A.A and glycerol from triglyceride lipids converted to glucose in liver
  23. Glucose removal ways
    • Resp substrate
    • Conversion to glycogen in liver for storage
    • Conversion to fats for storage
  25. SITE OF REGULATION: PANCREAS (islets of Langerhans)
    each islet consists of 2 types of cells : alpha cells glucagon (large and peripheral) beta cells insulin (smaller and at core)
  26. Insulin
    • Secreted due to increasing blood glucose level (detected by beta cells)
    • Inactive prohormone hydrolysis and removal of specific A.A form insulin
    • Insulin = protein consisting of 2 polypeptide chains joined by disulphide bonds
    • Insulin enters bloodstream, combines with plasma protein (beta-globulin) to prevent breakdown.
    • Increases membrane permeability to glucose by facilitating entry of glucose into muscle cells and adipose tissue.
    • Binding of insulin to receptors on target cells leads rapidly to fusion of vesicles found in cytoplasm to plasma membrane.
    • Glucose transporters proteins embedded in the membrane of these vesicles are rapidly inserted into the cell surface membrane, thereby giving cell an ability to efficiently take up glucose.
  27. Insulin
    • stimulates an increase in rate of glycogenesis in liver and muscles
    • inhibit breakdown of store glycogen leading to increase in storage of glycogen
    • stimulates an increase in rate of uptake of glucose by muscle and fat cells through increase in cell membrane permeability(by increase in glucose transporters in plasma membrane)
    • Stimulates an increase in rate of protein synthesis through A.A uptake by liver and muscle cells, fat synthesis from glucose by adipose cells
    • Stimulates and increase in formation of ATP DNA AND RNA (uses energy)
  28. Glucagon
    • 29 AA polypeptide
    • triggered by drop in blood glucose level and increasing AA levels
    • TARGET ORGAN : LIVER (acts through cAMP)
    • Promotes glycogenolysis and gluconeogenesis
  29. Signal Transduction Pathway
    • Process by which any chemical signal on cell's surface is translated into changes in the cell
    • 3 stages : reception, transduction and response
  30. Reception
    chemical signal binds to cellular glycoprotein, usually at cell surface
  31. Transduction
    binding leads to change in receptor that triggers a series of changes along a signal transduction pathway
  32. Response
    transduced signal triggers specific cellular activity
  33. Specificity
    A cell targeted by a particular signal has molecules of a receptor protein that recognizes the signal molecule
  34. Signal molecule
    • behaves as a ligand
    • complementary in shape to specific site on receptor and attaches there
  35. Binding
    causes receptor protein to undergo change in conformation -> directly affect receptor so it can interact with another molecule
  36. Signal receptors (plasma membrane proteins) :
    • G protein linked Receptors (glucagon)
    • Tyrosine Kinase Receptors (insulin)
    • Intracellular Receptors (Steroid hormone)
  37. G protein linked receptors
    • Binding of appropriate extracellular signal to G protein linked receptor activates receptor
    • Receptor binds to and activates a specific G protein located on cytoplasmic side of membrane
    • Activation takes place when a GTP nucleotide replaces the GDP bound to the G protein
    • G protein then activates a membrane bound enzyme after which it hydrolyzes its GTP and becomes inactive again
    • Activated enzyme triggers next step in pathway to cell's response
  38. Tyrosine Kinase Receptors
    • TK enzyme that transfers phosphate groups from ATP to A.A tyrosine on a protein
    • Ligand binding causes 2 receptors to form dimer
    • Activates TK protein portions of each polypeptide which phosphorylate the tyrosines on each other's cytoplasmic tails
    • Different relay proteins now bind to specific phosphorylated tyrosines and become activated, triggering different transduction
  39. Intracellular Receptors (lipid soluble, steroid)
    • Hydrophobic chem messengers cross cell surface membrane and bind to receptors in cytoplasm or nucleus
    • steroid hormones activate receptors that function as transcription factors regulating gene expression
  40. Activation of G protein linked receptor
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  41. Activation of Tyrosine Kinase Receptor
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  42. Transduction stage
    converts signal to a form that brings about specific cellular response
  43. Protein phosphorylation
    Phosphorylation is a cellular mechanism for regulating protein activity
  44. Protein kinase (PK) (bulk of relay molecules)
    enzyme that transfers phosphate grps from ATP to protein
  45. Signal transmitted by
    cascade of protein phosphorylations, each bringing with it a conformational change (usually change protein from inactive to active)
  46. Protein phosphatases
    enzymes that remove phosphate groups from proteins (Shut down signalling pathways when extracellular signal is no longer present)
  47. Second Messengers
    • small, non protein, water soluble
    • cyclic AMP (cAMP) and Ca2+ ions
  48. Binding of signal molecule (first hormone) to receptor
    • causes enzyme adenylyl cyclase to become activated
    • adenylyl cyclase then converts ATP to cAMP
    • cAMP activates protein kinase -> phosphorylates other proteins

    cAMP -> AMP through phosphodiesterase in the absence of signal molecule
  49. Insulin Receptor and its Response
    • Receptor : TK
    • Functions as enzyme that transfers phosphate grps from ATP to tyrosine residues on the protein subunits
    • Binding of insulin to receptor results in formation of a dimer and cross phosphorylation of subunits, activating catalytic activity of receptor
    • Activated receptor then phosphorylates a number of intracellular proteins, which then alter their activity, generate biological responses such as (FUNCTIONS OF INSULIN)
  50. Glucagon Receptor and its Response
    • Receptor: G Protein linked receptor (in liver cells)
    • Binding of glucagon to receptor on cell surface membrane activates set of G protein -> activates adenylyl cyclase
    • Activated AC convert ATP to cAMP, increasing cAMP concentration
    • Result in activation of protein kinases which then phosphorylate enzymes leading to (FUNCTIONS OF GLUCAGON)
  51. Signal amplification via signal transduction pathway - cascade effect
    1 signal molecule binds to a cell surface receptor

    Activate many G protein molecules

    Each activated G protein molecule activates a molecule of adenyl cyclase

    This produce a large amount of cAMP

    Each cAMP in turn activates a protein kinase

    Each protein kinase phosphorylates and activates several copies of a specific enzyme

    Each of these enzymes can then catalysed many chemical reactions
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