homeostasis & cell signalling

• homeostasis

  maintenance of a stable internal environment, independent of fluctuations in external environment by self-regulating & negative feedback so that organism can function optimally
• homeostasis

  when BGL increases aboce set point of around 90 mg / dL, displacement is detected by beta cells of islets of langerhans in pancreas. beta cells in response will secrete more insulin via exocytosis into the bloodstream.

  insulin will be transported via circulatory system to its target tissues, where it binds to cell surface receptors. this triggers a cascade of intracellular signalling events to bring about a response
• insulin responses

  1. glucose transporters (GLUT4) inserted into csm, increasing permearbility of cell to glucose, increasing glucose intake
  2. increase glycolysis, increase glycogenesis (glu->gly, cat by glycogen synthase), decrease gluconeogenesis (synthesise glu from other non-carb sources)
  3. decrease FA released and increase lipid (FA+glycerol) synthesis, increase transport of a.a into cells for protein synthesis
• glucagon responses

  1. increases glycogenolysis (gly->glu), increase gluconeogenesis
  2. increase rate of breakdown of lipids in adipose tissues
• steps of cell signalling

  1. ligand-receptor interaction
  2. signal transduction
  3. cellular response
  4. termination of cellular response
• termination


  stage 1: enz in extracellular space may degrade ligand, preventing ligand receptor interaction OR ligand receptor complex can be taken into cell via endocytosis

  stage 2: increase activity of phosphatases to dephos relay proteins, inactivating relay proteins OR use inhibitors that bind to ligand receptor complex/ relay prot, preventing signal transduction
• imptance of removing a bound ligand after a cellular response has been triggered

  if ligand remains bounded to a receptor, it will continue to trigger signal transduction, leading to excessive cellular response.

  cells can only respond to new ligands when bound ligand removed
• • a single polypeptide with an extracellular N-terminus, and an intracellular C-terminus.
  • a globular, seven pass transmembrane protein with a tertiary structure.
  • consists of 7 α-helices connected by three intracellular and three extracellular peptide loops.
  • The extracellular loops have a ligand binding site at which a specific signaling molecule (e.g. glucagon) can bind to the GPCR.
  • The intracellular domain of GPCR has a G protein binding site that allows binding of a heterotrimeric G protein complex.
• second messengers

  • small, non-protein, water soluble molecules or ions
  • can readily spread throughout cell via diffusion an d activate cellular proteins
• glucagon and GPCP (G-protein coupled receptor)

  • a decrease in BGL level below 90mg/dL detected by alpha cells in IOL of pancreas which secretes glucagon which recognises and binds to extracellular ligand-binding site csr, GPCR, on liver cell
  • causing GPCR to undergo confo change in intra domain of receptor, causing inactive G protein to bind to GPCR, causing a GTP mol displace bound GDP mol, causing confo change in G protein, activating it
• • activated G protein dissosiates from receptor and translocates along cytoplasmic side of csm to bind and thus activate enzyme adenylyl cyclase
  • adenylyl cyclase catalyses conversion of ATP to cAMP, which activates protein kinase A (PKA), activated PKA can phosphorylate other proteins
• G protein has intrinsic GTPase activity to hydrolyse GTP to GDP and inactivate G protein, termination
• • an increase in BGL ... which secretes insulin which recog and binds to extracellular ligand-binding site of csr, receptor tyrosine kinase (RTK), which exists as linked dimers on liver cells
  • causing confo change in intra domain of RTK, activating tyrosine kinase in each subunit, triggering crossphosphorylation.
  • phosphorylated tyrosine residues serve as docking sites for other relay proteins. relay proteins activated by binding to or phospho by PTR
  • activated relay prot may be kinases which can go on to phospho other proteins
• 1. Facilitates signal amp: small no. of signal mols binding to receptor can prod large cellular response as no. of activated mols increases with each catalytic step in pathway
  2. One signal mol can trigger many ST pathways in a cell and elicit many diff CR
  3. many checkpoints for regu as cellular responses can be termi/regu at reception or during ST
  4. ensures specific rxns are triggered as a specific signal will bind to a specific receptor and will elicit specific reactions in specific cell types.
  5. A signal mol can activate genes in nucleus upon binding to csr without the need to move into nucleus.
• signal transduction


  series of changes in cellular proteins, that convert the extracellular chemical signal into an intracellular response. binding of ligand to receptor causes confo change in intracellular domain of receptor, initiating ST
• phosphorylation cascade


  sequence where 1 enzyme phosphorylates another