lecture 1 biochemistry (week 2) Flashcards
describe the pathway of senses (smell, taste, and vision)
stimulus –> receptor protein activation –> enzyme cascade (in some cases), ion channel action (in others) –> cellular response –> nerve conduction, brain circuitry, behavioural response
describe GPCRs as sensory receptors
cell growth –> inactivation of adenyl cyclase (cytosolic AMP decrease) –> cell motility
cell growth and motility –> activation of adenyl cyclase (cytosolic AMP increase)
cell proliferation - activation of PLC beta (increase of intracellular Ca)
cancer progression and metastasis - strong activation of the GTPase
PLC beta, P3K, ion channel –> desensitization and apoptosis
who earned nobel prizes in physiology and medicine in 2004? and what for?
richard axel
linda d buck
for their discoveries of odorant receptors and the organization of the olfactory system
describe smell/olfaction
the olfactory epithelium includes exposed olfactory sensory neurons which are highly ciliated
humans have about 400 functioning olfactory receptors which are expressed on cilia, picking up odorants
describe olfaction in each olfactory sensory neuron
each neuron only expresses one type of olfactory receptor
Golf is the alpha subunit of the heterotrimeric complex linked to Olf Receptors –> stimulates Adenylyl Cyclase
cAMP opens cation channels leading to depolarization and action potential propagates into the olfactory bulb in the brain
describe the olfactory network connections
thousands of sensory neurons, only 400 receptors
all neurons expressing one particular olfactory receptor converge on their own discrete area in the olfactory bulb
again, another developmental mystery –> how this complicated wiring doesn’t get confused
also, there must be ‘amplitude sensing’ at the level of neuron and clusters of neurons –> how ‘strong’ a smell is
what is the olfactory code?
how different smells/ligands are recognized by specific groups of receptors
similar ligand structures can therefore elicit very different smell responses
describe the sense of smell in other parts of the body
odorant receptor hOR 17-4,
previously shown to interact with the floral odour ‘bourgeonal’ –>
role in guiding sperm to the egg.
receptors present in heart muscle cells may be a metabolic regulator of heart function.
receptors activated in the immune system have been seen to promote the death of certain types of leukaemia cells.
receptors in the skin increase the regeneration of skin cells and help wound healing.
receptors in the digestive tract may cause chronic diarrhoea or constipation but may also contribute to better digestion.
describe how taste may have saved our ancestors’ lives
gustation’ senses components in your food
you want nutrition but not to be poisoned –> behavioural response needs to be quick
sour and bitter –> possible toxins/acidity –> may be an acquired taste like coffee
umami (savoury taste from some L-amino acids = MSG)
hedonic (pleasure) or homeostatic (good for you) eating interacts with taste (palatable/aversive) and state (hunger/satiety
what are the taste receptors and what specific taste do they correspond to?
T1R1+T1R1 – umami (l amino acids, glycine, L-AP4)
nucleotide enhancers
T1R2+T1R3 – sweet (sucrose, fructose, glucose), artificial sweeteners (saccharin, cyclamate), d amino acids, glycine, sweet proteins
30 T2Rs – bitter (cycloheximide, denatonium, salicin, PTC, saccharin, quinine strychnine atropine)
ENaC – sodium, low NaCl sodium salts
sour and carbonation cells – PKD2L1 (acids), CA Iv (carbonated drinks)
what happens to the taste cell when the receptor is activated?
the cell is depolarized, by TRPM5; a calcium activated non selective cation channel, that induces depolarization when calcium is increased intracellularly
what do taste responses depend on?
the taste cell type, not the receptor
describe the experiment done to prove this
artificial GPCR called Receptor activated solely by a synthetic ligand (RASSL) experiments
has a ligand (spiradoline) is normally tasteless.
artificially express RASSL in mouse sweet or bitter taste cells
the mouse reacts according to cell type, not the ‘actual’ taste
same receptor + same ligand elicit different responses based on the nature of the cell
what are the taste/smell diseases?
hyposmia/anosmia/dyosmia - smell
hypogeusia/ageusia - taste
ageing, COVID-19, mineral deficiencies, Parkinson’s, psychiatric conditions
faculties are non essential
what are the main parts of the eye?
lens, retina, iris
what are some of the diseases in case of eye anatomy going wrong?
astigmatism, presbyopia, myopia, amblyopia, glaucoma, retinal detachment
describe the anatomy of the retina
optic nerve
ganglion cells
amacrine cells
bipolar cells
horizontal cells
cones and rods – photoreceptors
what is the rhodopsin gene?
it is the receptor
and a photon of light is the ‘ligand’
contains a chromophore called retinal
located in within the TMDs of rhodopsin
light induces cis retinal –> trans retinal
induces a conform change in rhodopsin
triggering the heterotrimeric G protein signal transduction cascade
trans retinal dissociates from the rhodopsin and undergoes enzymatic recycling back to its cis form
how does hyperpolarisation signal to the brain?
normal nerve signalling operates by depolarisation (action potentials).
here, it’s about ending the inhibition of the neighbouring Bipolar Cell.
the prevention of the glutamate neurotransmitter release, uninhibits the bipolar cell and allows a signal to the brain
describe the photoreceptors
rods – low light amd motion (express rhodopsin)
cones – differentiate colour and detail (express different opsins)
long cones - red
medium cones - green
short cones - blue
RGB
what are the diseases of the retina/signalling?
night blindness due to deficiency in Vitamin A - which is converted into retinal
age-related macular degeneration
wet = vasculature leakage problem
dry = (ageing) thinning of macular and deposition of Drusen material
diabetic retinopathy: microvasculature damage in the retina.
very common form of loss of vision.
colour blindness (achromatopsia) is more common in males because cone genes are on X chromosome (no second X to compensate in males)
what does OPN4 do?
encodes melanopsin in the retina
expressed in retinal ganglion cells
not for image formation
Senses light, but more for day/night differential = ‘entrainment’ of your body clock
these cells can signal to the Suprachiasmatic Nucleus (SCN) in the brain
describe the anatomy of the ear
outer – pinna
middle – incus, malleus, stapes
inner – cochlea (hearing), organ of corti, semi-circular canals (balance), macula and crista ampullaris
how does hearing work?
sound waves
tympanic (ear drum) membrane
ossicles transmit & amplify
fluid waves (intensity and pitch) activate hair cells via mechanical opening of bridge protein channels on cilia.
signal to cortex.
