Homeostasis and Cell Signalling

Question 1

Homeostasis

Answer 1

refers to the maintenance of a stable internal environment independent of fluctuations in the external environment by self-regulating and negative feedback mechanisms so that the organism can function optimally

Question 2

Advantages of cell signalling pathway

Answer 2

• a small number of ligand molecules can trigger a large cellular response due to signal amplification where the number of activated molecules increases with each catalytic step
• a specific ligand can bind to a specific receptor which can trigger a specific cellular response
• allows many checkpoints for regulation:
  1. phosphotases that inactivates kinases
  2. endocytosis of receptor
  3. endocytosis of ligand-receptor complex
  4. production of inhibitors. that bind to intracellular domain of LRC
• one specific ligand molecule can trigger multiple transduction pathways, and elicit many different cellular responses
• can activate genes in the nucleus without the need to move into the nucleus

Question 3

Effects of Insulin

Answer 3

when glucose levels increase above set point, this is detected by the B cells of islets of Langerhans of pancreas –> secrete insulin –> insulin will recognise and bind to specific ligand - binding site of the tyrosine kinase receptor which is complementary in shape –> ligand binding causes a change in conformation of the intracellular cytoplasmic domain of the ligand receptor complex which activates the tyrosine kinase in each of the subunits –> this triggers crossphosphorylation of the tyrosine residues –> phosphorylated tyrosine residues act as docking sites for other relay proteins to be phosphorylated and hence activated –> some relay proteins include kinases which can go on to activate other relay proteins –> phosphorylation initiates the sequential activation of kinases, resulting in a phosphorylation cascade which eventually activates glycogen synthase which catalyses the synthesis of glycogen from glucose, translocation of glucose transporters from the membrane of the cytoplasmic vesicles to the cell surface membrane –> increases glucose intake into cells as it increases permeability of the cell to glucose, increased rate of glycolysis, and lipid and protein synthesis –> blood glucose levels decrease, detected by B cells which decreases insulin production

Question 4

Effects of glucagon

Answer 4

decrease in blood sugar levels –> detected by a cells of islets of Langerhans of pancreas –> secrete glucagon –> which recognizes and binds to ligand binding site of G-protein coupled receptor which is complementary in shape –> induces a conformational change in the intracellular cytoplasmic domain of the GPCR which then causes the binding of inactive G protein to bind to it and release bound GDP to replace with GTP, hence activating it —> dissociates from GPCR and translocates along the cytoplasmic side of the cell membrane until it binds to and activates adenylyl cyclase which converts ATP to cAMP which activates protein kinase A –> activation of protein kinase A. triggers a sequenial activation of kinases, leading to a phosphorylation cascade until it reaches glycogen. phosphorylase which breaks down glycogen into glucose, increases rate of gluconeogenesis –> blood glucose levels increase, detected by a cells which reduce secretion of glucagon

Question 5

Role and nature of second messenger

Answer 5

• small, non-protein, water soluble molecules or ions
• can readily spread through the cell via diffusion and activate cellular proteins
• can participate in pathways initiated by both GPCR and RTK

Question 6

structure and function of GPCR

Answer 6

• GPCR is consists of a single polypeptide folded into a globular protein with an extracellular N terminus and an intracellular C terminus
• GPCR is a globular, seven pass transmembrane protein with a tertiary structure
• consists of 7 a helices
• extracellular loops have a ligand-binding site at which specific signalling molecule, the intracellular domain of the GPCR has a G protein binding site
• when a ligand binds to the ligand-binding site of the extracellular side of a GPCR, it induces a conformational change in the intracellular domain
• bound G protein is activated by exchanging bound GDP for GTP