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Cell Signaling (BIO-203)Lecture 5
Signal amplification occurs in many signaling pathways Receptors are low abundance proteinsThe binding of few signaling molecules to
available receptors require production of tens of thousands or even millions of second messenger or activated enzyme molecules per cell.
Substantial signal amplification must occur in order for a hormone signal to induce a significant cellular response.
For example, a single epinephrine-GPCR complex causes conversion of up to 100 inactive Gαs molecules to the active form before epinephrine dissociate from the receptor.
•Binding of a single epinephrine molecule to the receptor induces synthesis of a large number of cAMP molecules, first level of amplification.•2 molecules of cAMP activate 1 molecule of protein kinase A.•Each activated PKA phosphorylates and activates multiple product molecules, second level of activation.
Iron uptake in different cells
Diferric Tf in
serum
Macrophage
Hepatocyte
Duodenal enterocyte Endosome
pH < 6 Ferritin
Ferritin
Dcytb
HCP1
HO
Haem
Apo Tf in serum
Haem from RBCs
Ferritin
HO
Diferric Tf
Fe3+ Fe2+
Haem
FPN1
Fe-Tf-TFR1
MCFhephaestin or ceruloplasmin
DMT1
STEAP 3
GLUTGlucose transporter found in the plasma
membrane of erythrocytes. 12 GLUTS are encoded by human genomes.
Glucose conc. is high in the extracellular medium than in cell.
GLUT alternates between 2 confirmational states.
Insulin and glucagon work together to maintain a stable blood glucose level
The entry of glucose into pancreatic β cells is mediated by GLUT2
Basal blood glucose level is approximately 5mM. The Km value (an indicator of the affinity of the transporter protein for glucose molecules; a low Km value suggests a high affinity).
The Km for glucose of GLUT2 is 20mM, a rise in extracellular glucose from 5 mM causes an increase in glucose intake.
The conversion of glucose into pyruvate is accelerated resulted in an increased production of ATP in the cytosol.
The binding of ATP to ATP-sensitive K channels closes these channels.
Closed channels reduced the efflux of K ions from the cell which triggers the opening of Ca channels.
The influx of Ca ions raises the cytosolic Ca levels which triggers the fusion of insulin-containing secretory vesicles with the plasma membrane and secretion of insulin.
How do we measure the affinity of a receptor to its ligand?
How a maximal cellular response to a signaling molecule achieved?
What do binding assays tell us?