Signalling In Disease Flashcards
Which 2 factors cause loss of control
Genetics eg mutations
Disease eg cholera or pertussis
Are all gpcr in all cells
No which causes either localised or systemic effects
How do gpcr change overtime
Levels of exp change during development
What are orphan receptors
Receptors that are close to structure as other gpcr but don’t have an identified ligand
Which 2 things cause hyperthyroidism
Overproduction of tsh/thyrotropin
Or failure of tsh gpcr to inactivate
What is the diabetes called which has lack of response /lack of ligand arginine vasopressin / ADH
Nephrogenic diabetes insipidus
What 3 things are in nephrogenic insipidus
Under production of ADH
Inability for receptor to recognise ligand
Inability for receptor to activate G protein to activate adenylyl cyclase
Where do ligands bind on gpcr
Exo loops or n terminal
What part of a gpcr binds with a G protein
Cytoloops and c terminus
What is bound to rhodopsin gpcr
11 CIS Retinal
What G protein associates which rhodopsin
Transducin
What happens to retinal and receptor when light hits
Converts 11 CIs to all trans retinal
And conformational change in receptor
What is the importance of activation of G protein transducin in rhodopsin
Activates pde converting cgmp to 5’gmp
This blocks the na cation channel and hyperpolarisation cell = activated neurone
What determines wavelength of light perceived by rhodopsin
Where retinal binds on the 7 tm domain on the lysine residue
The aa sequence surrounding it
How many aa determines diff between red and green wavelength perceived by rhodopsin
3 aa around the 7 tmd lysine where retinal binds
Why is red green colour blindness often in males
X linked and they need only 1
Why can recomb of red and green receptor genes occur
They are nearly homologous except 3 aa
Explain the 2 types of recomb occurring
Recomb where there’s unequal recomb and one x has more red copies and no green copies etc
Recombination within genes to form hybrids of red and green gene in one
What G protein mutation causes night blindness
G a transducin (can’t activate pde)
What g alpha subunit causes defects in blood clotting
G alpha 12
What is caused by a mutation in a B3 subunit
Hypertension
What mutation causes adrenal cortical tumours
Ai2
What syndrome is caused by mutation in the g alpha s subunit (activates pka)
Mccune Albright syndrome
What 2 diseases cause modification in g subunits
Cholera vibrio cholera - gas subunit
Pertussis bordatella whooping cough - gai subunit (inhibitory)
What type of toxin is cholera
Hetero oligomeric - a and b exotoxin
Which subunit of the cholera toxin enters cell
A subunit
Which part of a subunit causes chemical mod of the gas subunit
CTa1 cholera toxin a1
What does cta1 do to gas
Nad dependant adp ribosylation before the gtp site On a subunit
Causes constant activation of adenylyl cyclase
How does cholera cause diarrhoea and dehydration
Camp increase causes Cl efflux out of cells
What type of bacteria is cholera vibrio
Gram -ve rod
What effect does increased camp have in cardiac
Increase in camp eg via SNS causes increase in contraction rate via increase in ca influx of ion channels etc
How is camp important in kidney
V2 binding of ADH causes camp increase to increase aqueous channels in lumen for reabsorption
What does camp do in bone when it’s increased by parathyroid binding
Increased reabsorption of ca in bone
How does camp caused increase glucose
Lipolysis, phos of phosphorylase, phos of glycogen synthase
How is phospholipase c terminated
Degradation into ip2 or phos into ip4
How is type 2 diabetes different
Can produce insulin but they’re not responding to it
What has been suggested to cause resistance
Increase in ffa/ fat diet/ increase in adipose cells
Which populations have high type 2 occurrence
Pimas and aborigines
Which hormones reduce appetite released by adipocytes
Leptin and adiponectin
What tissue is the only one to increase overtime
Adipose
What are adipokines for released for adipocytes
Lipid metabolism, appetite roles, glucose homeostasis, angiogenesis,immune system, ecm metabolism
Is having no fat stores good
No also causes diabetes
Why is mutations in signalling unlikely for type 2
Would be present at birth
How is randles cycle / change in metabolic preferences a potential cause of diabetes
Competition of ffa and glucose to get b oxidated
If more fa then glucose can’t get oxidated and glycolytic enzymes get blocked
