foundation I

Question 1

implication of 2nd law of thermodynamics for cells

Answer 1

• 2nd law states that total entropy of a system increases over time
  (i.e. tends towards DISORDER)
• INPUT of energy is required to counteract entropy
  and maintain the highly organised stuctures found in cells

Question 2

which of the following ligands bind to intracellular receptors?
A) water-soluble hormones (e.g. insulin, epinephrine)
B) cytokines (e.g. JAK-STAT)
C) lipophilic hormones
D) growth factors (e.g. TGF)

ligands must diffuse across the lipid bilayer to do so

Answer 2

C) lipophilic hormones

examples include
* steroid hormones (e.g. estrogen)
* thyroid hormone
* vitamins (e.g. vit D, retinoic acid — active form of vit A)

Question 3

describe Ras-MAPK signaling pathway:
1. binding of (…) to Receptor Tyrosine Kinase (RTK) on cell surface
2. inducing (…) and thus activation of RTK
3. intracellular (…) domains of RTKs then undergo (…)
4. which allows it to bind (…)
5. and subsequently activate (…) by binding to it and promoting the exchange of (…)
6. ending in the MAPK cascade ((…) -> (…) -> (…) -> (…))
7. (…) then translocates to nucleus and activates transcription factors

Answer 3

1. binding of growth factor to Receptor Tyrosine Kinase (RTK) on cell surface
2. inducing dimerization and thus activation of RTK
3. intracellular tyrosine kinase domains of RTKs then undergo auto or cross-phosphorylation
4. which allows it to bind adaptor proteins
5. and subsequently activate Ras by binding to it and promoting the exchange of GDP for GTP
6. ending in the MAPK cascade (Ras -> Raf -> MEK -> ERK)
7. ERK then translocates to nucleus and activates transcription factors

Question 4

Which one of the following activating variations will MOST LIKELY be observed in cancer cells?

A) Increased Ras exchange of GTP for GDP
B) Increased phosphorylation of Raf kinase
C) Increased nuclear translocation of Ras
D) Decreased dimerization of the Ras
E) Decreased binding of Ras to Erk

Answer 4

B) Increased phosphorylation of Raf kinase

the change will always be Ras remaining in active GTP-bound state
→ constant activation of Raf, then MEK and finally ERK
→ ERK translocates to nucleus and promotes gene transcription for uncontrolled cell division

Question 5

describe GPCR signaling pathway:
1. ligand binds to extracellular domain of GPCR
2. inducing a (…) and thus activation of the (…) bound to GPCR,
and thus resulting in exchange of (…)
and the dissociation of the (…) subunit from the (…) subunit
3. the (…) subunit then activates (…),
which converts (…)
4. (…) then activates (…),
which goes on to phosphorylate target proteins

Answer 5

1. ligand binds to extracellular domain of GPCR
2. inducing a conformational change and thus activation of the G-protein bound to GPCR,
   and thus resulting in exchange of GDP for GTP
   and the dissociation of the α subunit from the βγ subunit
3. the α subunit then activates adenylyl cyclase,
   which converts ATP to cAMP
4. cAMP then activates protein kinase A (PKA),
   which goes on to phosphorylate target proteins

Question 6

how is GPCR signaling terminated

Answer 6

α subunit hydrolyses GTP to GDP
→ return of G-protein to inactive state
→ also reassociation of α and βγ subunits