lecture 1 biochemistry (week 2)

Question 1

describe the pathway of senses (smell, taste, and vision)

Answer 1

stimulus –> receptor protein activation –> enzyme cascade (in some cases), ion channel action (in others) –> cellular response –> nerve conduction, brain circuitry, behavioural response

Question 2

describe GPCRs as sensory receptors

Answer 2

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

Question 3

who earned nobel prizes in physiology and medicine in 2004? and what for?

Answer 3

richard axel

linda d buck

for their discoveries of odorant receptors and the organization of the olfactory system

Question 4

describe smell/olfaction

Answer 4

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

Question 5

describe olfaction in each olfactory sensory neuron

Answer 5

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

Question 6

describe the olfactory network connections

Answer 6

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

Question 7

what is the olfactory code?

Answer 7

how different smells/ligands are recognized by specific groups of receptors

similar ligand structures can therefore elicit very different smell responses

Question 8

describe the sense of smell in other parts of the body

Answer 8

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.

Question 9

describe how taste may have saved our ancestors’ lives

Answer 9

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

Question 10

what are the taste receptors and what specific taste do they correspond to?

Answer 10

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)

Question 11

what happens to the taste cell when the receptor is activated?

Answer 11

the cell is depolarized, by TRPM5; a calcium activated non selective cation channel, that induces depolarization when calcium is increased intracellularly

Question 12

what do taste responses depend on?

Answer 12

the taste cell type, not the receptor

Question 13

describe the experiment done to prove this

Answer 13

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

Question 14

what are the taste/smell diseases?

Answer 14

hyposmia/anosmia/dyosmia - smell

hypogeusia/ageusia - taste

ageing, COVID-19, mineral deficiencies, Parkinson’s, psychiatric conditions

faculties are non essential

Question 15

what are the main parts of the eye?

Answer 15

lens, retina, iris

Question 16

what are some of the diseases in case of eye anatomy going wrong?

Answer 16

astigmatism, presbyopia, myopia, amblyopia, glaucoma, retinal detachment

Question 17

describe the anatomy of the retina

Answer 17

optic nerve

ganglion cells

amacrine cells

bipolar cells

horizontal cells

cones and rods – photoreceptors

Question 18

what is the rhodopsin gene?

Answer 18

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

Question 19

how does hyperpolarisation signal to the brain?

Answer 19

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

Question 20

describe the photoreceptors

Answer 20

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

Question 21

what are the diseases of the retina/signalling?

Answer 21

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)

Question 22

what does OPN4 do?

Answer 22

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

Question 23

describe the anatomy of the ear

Answer 23

outer – pinna

middle – incus, malleus, stapes

inner – cochlea (hearing), organ of corti, semi-circular canals (balance), macula and crista ampullaris

Question 24

how does hearing work?

Answer 24

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.

Question 25

how does balance/equilibrium function

Answer 25

utricle and saccule (otolith organs) with maculae (sensory receptors) for linear acceleration and head position

semi-circular canals and ampullae with cristae ampullaris (sensory receptors) for rotational acceleration

maculae and Crista ampullaris receptors are very similar to organ of corti receptors

however: gravity & acceleration provide force to move the cilia

Question 26

describe the touch system

Answer 26

free or encapsulated nerve dendritic endings

in skin and deep organs, e.g.: Pacinian corpuscles,

meissner corpuscle

large receptive field detects vibration of moving touching…not stationary touching.

opens mechanically-gated sodium ion channel

action potential generated

Question 27

describe how temperature is detected

Answer 27

thermoreceptors

free dendritic endings in hypodermis

function in thermoregulation (body temp. control)

temperature-gated ion channels

chemical ligands can also stimulate these channels

Question 28

describe how pain is detected

Answer 28

free dendritic endings

activation by strong, noxious stimuli - Function?
3 categories:
mechanical
thermal (menthol and cold / capsaicin and hot) as in previous slide
chemical (includes chemicals from injured tissues)

inflammatory Pain

may activate 2 different pathways:
reflexive protective – integrated in spinal cord
ascending to cortex (pain or pruritis/itching)