exam 1 medchem class 4

what happens after GPCR is activated

G-protein trimer (has alpha, gamma, beta subunits) relays the signal: then secondary messengers are activated (eg cAMP, Ca2+, PI) which lead to diverse biological responses

downstream response options after GPCR

short term responses from protein kinases, immediate early gene mRNA after transcription, immediate early gene protein after translation, dimerization and post-translational modification, long-term gene responses

how does the g-protein trimer relay the signal

alpha subunit can activate target protein, activated beta-gamma complex can open a K+ channel, alpha subunit can stop the signal also (with intrinsic GTPase activity- by hydrolysing its bound GTP to GDP, inactivating and reassociating with the beta-gamma dimer)

g protein cycle

basal state - agonist binding leads to association and GTP-GDP exchange which - leads to dissociation where the alpha and beta-gamma subunits are effectors - then GTPase activity of alpha subunit returns it to basal state

Galpha-s mediated signaling

adenylate cyclase system - activates adenylyl cyclase - cAMP - PKA - multiple physiological effects - inc. smooth muscle relaxation

bonds that histamine can have

• Ionic w/ NH3+ they become protonated

• Can form an amino compound w/ negative charge aa (aspartame and glutamate)

• N and HN can do H bonds

  • Aromaticity can do van der waals bonding

what are actions of cAMP

cell-type dependent, depend on different PKA protein substrates

eg of physiological actions of cAMP following GCPR activation

adrenaline increases heart rate

Galpha-q mediated signalling expl

• Once Gq protein gets activated

  • Alpha subunit is activating enzyme - PI-PLC - Is breaking down a phospholipid

    • PIP2 - polar head of phospholipid, part of membrane

    • Very polar head that has been cleaved off

    • Now have IP3

    • Rest of phospholipid - DAG -

      • Activates protein kinase (PKC)

        • Phosphorylation of proteins

      • Goes on till Gq protein stops being activated

How can you measure PLC activation?

via Ca2+ levels inside the cell

3 notes of intracellular Ca2+

very important 2nd messenger in cells, many proteins sensitive to its concentration in the cytoplasm, its concentration is tightly regulated

example of an important Ca2+ sensitive protein

Calmodulin - can bind Ca2+ and then change conformation and eg bind target proteins

CaM-kinase dependent NO synthesis (4 steps)

Ach binds muscarinine receptor (GPCR) - signalling via PLC gives Ca2+, Ca2+ binds calmoduline, calmoduline activates CaM-kinase, CaM-kinase activates NO synthase, etc.

molecular basis of sight

chromophore changes upon illumination - GPCR is the mediator from proton to “molecular movement”

from photon to electric signal

membrane outer segment has cation selective ion channel - open in the dark, Na+ influx, depends on cGMP levels; proton inhibits Na+ influx (activation of cGMP-specific PDE via G protein, membrane hyperpolarization); hyperpolarization transferred to synaps

how do we see different colors

3 kinds of cones - diff proteins

how to do signal termination with a: transmitter

breakdown/re-uptake

how to do signal termination with a: g protein

intrinsic GTPase activity

how to do signal termination with a: second messenger

breakdown

how to do signal termination with a: protein

dephosphorylation

how to do signal termination with a: receptor

regulation of function and localization

GC and AT pairing in DNA - how many bonds, which

GC - 3 H bonds
AT - 2 H bonds