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1st year: Physiology and Metabolism > signal transduction (Spooner) > Flashcards

signal transduction (Spooner) Flashcards

1
Q

why do regulatory feedback pathways exist?

A

positive feedback may be the response so need to control this and damp down signals or turn off receptor

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2
Q

signals are usually….

A

ligands that bind to something like receptor (except for light)

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3
Q

agonists

antagonists

A

ligands that stimulate pathways, most natural ligands like serotonin
ligands that inhibit pathways, most drugs like antihistamine

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4
Q

direct contact

A

direct contact - ligand on signalling cell binds receptor on target cell, important in development

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5
Q

gap junction

A

exchange signalling molecules, like in neurones

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6
Q

autocrine

A

ligand induces response only in signalling cell
self-stimulation - cell that makes signal is one that responds to signal
autocrine ligands rapidly degraded so short half life and can’t travel far

reinforce developmental decisions

common features of cancers

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7
Q

eicosanoids

A

autocrine ligands derived from fatty acids
aggregation of platelets in immune system
pain and inflammation
contraction of smooth muscle

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8
Q

paracrine

A

ligand induces response in target cells close to signalling cell

limited diffusion of ligand, destroyed by extracellular enzymes

e.g. neuromuscular junction

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9
Q

endocrine

A

ligand by endocrine cells and carried in blood (hormones)
distant target cells
systemic effect

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10
Q

what class of signals does acetylcholine belong to?

A

paracrine but also can be endocrine

so distinction between classes not always clear

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11
Q

specificity: cell-type specific

A

certain receptors only present on certain cells
molecules downstream of receptor only present in some cells (sometimes have receptor but don’t respond because lack further components)

because of differential gene expression by activators and repressors

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12
Q

specificity: high affinity interaction

A

precise molecular complementarity between ligand and receptor mediated by non-covalent forces

association depends on concentration

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13
Q

what is dissociation dependent on?

A

independent of conc of free reactants but dependent on conc of complex

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14
Q

1st order vs second order reaction

A

1 reactant vs 2 reactants

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15
Q

high affinity

low affinity

A

highly specific

less specific, sticky

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16
Q

signalling is incredibly…..

A

sensitive

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17
Q

desensitisation

A

continuous signal

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18
Q

cross-talk

A

pathways share common components so shared response

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19
Q

integration

A

multiple signals produce unified response
net response depends on integrated output of both receptors
takes strength of each into account

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20
Q

intrinsic enzyme activity

A

ligand binding activates enzyme activity

e.g. insulin receptor

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21
Q

insulin

glucagon and epinephrine (adrenaline) and cortisol

A

lowers blood sugar levels

raises blood sugar levels

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22
Q

islets of Langerhans:
alpha
beta
gamma

A

secrete glucagon
secrete insulin (more beta cells than alpha)
secrete somatostatin

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23
Q

IR

A

insulin receptor
associated into dimers
alpha subunit pointing out from membrane, beta in cytosol

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24
Q

IRS-1

A

insulin receptor substrate 1

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25
Grb2 | Sos
binds phosphate on activated IRS-1 guanine nucleotide exchange factor (GEF) - changes any guanine associated with the target
26
Ras
G protein, enzyme
27
what activates the same cascade as insulin?
EGF
28
what does insulin count as?
growth factor because activates CDKs
29
PI-3K what does it cause when activated?
phosphoinositide 3-kinase phosphorylates phosphotidylinositol 4,5 bisphosphate (PIP2) to produce phosphotidylinositol 3,4,5 triphosphate (PIP3) which recruits PIP3-dependent protein kinase (PDK1) which activates protein kinase B (PKB also called Akt)
30
second messenger
small metabolically unique molecule, not a protein, whose conc can change rapidly, relay signals from receptors to target molecules in cytoplasm or nucleus
31
growth factor
phosphorylation of IRS-1 amplifies signal and recruits and activates Ras so MAPK cascade, gene expression changes
32
glucose regulator
phosphorylation of IRS-1 amplifies signal, conversion of membrane lipids and amplification via lipid dependent kinase, activation of PKB upregulates glucose entry into cells and glycogen production
33
why are there 2 pathways involved in IR signalling?
there's no point in growing if there is no food supply
34
PTEN
PIPs-specific phosphatase removes phosphate at position 3 of PIP3 to convert to PIP2 so shuts off signalling through PKB
35
PKB
converts excess glucose to glycogen | transport of GLUT4 glucose transporter to membrane
36
Lipostat theory 1953 evidence?
adipose tissue decreases - feedback stimulates feeding behaviour (hunger) and reduced fatty acid oxidation (store it) LEPTIN released by adipose, binds to receptor in hypothalamus and tells brain you're full
37
Leptin discovery
Lep obese mice display physiological behaviour of starvation, diabetes, won't stop eating injection of leptin gene corrects obesity
38
anorexigenic
appetite-reducing neurones in hypothalamus
39
alpha-MSH
alpha-melanocute stimulating hormone modulates nervous transmission suppression of apetite, stimulate sympathetic NS
40
JAK
soluble Janus kinase cytosolic non-receptor tyrosine kinases, transduce cytokine-mediated signals via JAK-STAT pathway 2 phosphate transferring domains - 1 kinase, 1 negatively regulates kinase activity of 1st (Janus - god with 2 faces)
41
STAT
signal transducer and activator of transcription | activated by activated receptor
42
NLS
nuclear localisation signals
43
where does leptin signal other than the brain?
liver and muscle cells making them more sensitive to insulin | signals through IRS-2
44
EPO signalling?
erytropoietin hormone that under hypoxic (low O2) conditions, secreted to increase production of RBCs used to cheat in sport via JAK-STAT pathway using STATs
45
GPCR structure
``` G-protein coupled receptor same basic structure extracellular domains E1 to E4 transmembrane domains H1-H7 cytosolic domains C1-C3 and C4 tail ```
46
multiple heterotrimeric G-proteins
Gs - stimulates adenylate cyclase Gi - inhibits adenylate cyclase etc.
47
thinking errors
type 1 - believing a false (it's false but you think true) type 2 - rejecting a truth (it's true but you think false) physiological response promotes type 1 error e.g. run if there's a noise that might be a lion
48
cortisol
increases blood sugar through gluconeogenesis | suppresses immune system
49
cAMP
2nd messenger signalling molecule activates variety of proteins response depends on which target proteins are in cell activates protein kinase A (PKA) which targets proteins (transcription factors, ion channels, enzymes)
50
complex epinephrine signalling
Epinephrine binds: ① a β-adrenergic GPCR receptor coupled to a Gs heterotrimeric G protein: Gαs is activated and stimulates adenylate cyclase Gβs subunits inhibit adenylate cyclase ② an α-adrenergic GPCR receptor coupled to a Gi heterotrimeric G protein: Gαi is activated and inhibits adenylate cyclase Gβγi subunits activate a MAPK kinase cascade
51
3 ways to turn off adrenaline response
loss of ligand regenerates receptor alpha turns itself off adenylate cyclase converts G-alpha to inactive form
52
glucagon and adrenaline link
glucagon stimulates glycogen breakdown, which is the same response as adrenaline but long term slow response unlike adrenaline which is fast
53
CTx
cholera toxin binds to cell surface ganglioside lipid GM1 on intestinal epithelial cells endocytosis, goes to Golgi into ER PDI protein breaks disulphide bond that holds toxin subunits together, A1 subunit bound to BiP, dislocates but refolds when enter cytosol of cell CTxA modifies G-alpha-s ON permanently so adenylate cyclase always on, rise in cAMP, interfere with CFTR - diarrhoea
54
light reception
passes through neural layer through rods and cone cells | signal in discs of photoreceptive membrane in outer segment of retine
55
light receptor structure
inner and outer segments - primary cilium rod cells - non-colour vision and depth at low light intensity cone cells - colour, high light intensity
56
rod cells
outer segment has discs not connected to plasma membrane | disc is closed sac of membrane with photosensitive rhodopsin
57
rhodopsin
specialised GPCR made of opsin linked to 11-cis-retinal (prosthetic group which receives light) covalently attached to nitrogen in side chain of specific lysine residue of TM domain 7
58
mammalian rhodopsin
500nm peak absorbance rod cell respond to single photon 5 responses lead to register of flash of light
59
3 mechanisms that make rods insensitive to high light
prolonged cGMP-gated channel closure phosphorylation of opsin reduces transducin activation arrestin binding to phosphorylated opsin stops transducin activation
60
our colour vision
we are typically trichromats 414-426nm blue 530-532 nm green 560-563nm red
61
organism that can see the most colours
Mantis shrimp - Neogonodactylus oestedii | 16 pigments
62
sildenafil citrate
structure similar to cGMP so inhibits cGMP PDE so cause blue-tinged vision, can't tell blue and green apart also targets PDE-5 in corpus cavernosum (erectile tissue)
63
nitric oxide
activates guanylate cyclase inside cell by binding to haem group converts from GTP to cGMP - alters activity of target proteins
64
angina treatment today
``` glycrol trinitrate (nitroglycerine NG) cause dilation of blood vessels ```
65
high blood pressure and NO
autonomous nerves in vessel wall respond to high blood pressure and release ACh which binds to receptors on plasma membrane of endothelial cells - increases endothelial cell calcium - 2nd messenger - activates nitric oxide synthase (arginine to citrulline and nitric oxide)
66
nitric oxide synthase isoforms and functions
NOS1, nNOS, neuronal isoform - development of nervous system, protection against cardiac arrhythmia ,peristalsis and sexual arousal NOS2, iNOs, inducible isoform - produces large amounts of NO as a defence mechanism by macrophages, cause of septic shock NOS3, eNOS, endothelial isoform - controls vascular tone, insulin secretion, regulates angiogenesis, role in embryonic heart development and morphogenesis of coronary arteries and cardiac valves bNOS, bacterial NOS - protects against oxidative damage, immune attack
67
amyl nitrate
vasodilator vapourises to generate NO dilates vascular smooth muscle lowered blood pressure
68
cyclic nucleotides
2ndary messengers | control physiological processes like smooth muscle contractility
69
phosphodiesterases (PDEs)
superfamily of metallophosphydrolases that cleave 3',5'-cyclic phosphate moiety of cAMP/cGMP to produce 5' nucleotide
70
PDE5
increases blood pressure | target for succeful drug sildenafil citrate
71
4 types of oestrogen receptors
E1 - menopause E2 - reproductive years E3 - pregnancy E4 - pregnancy
72
tamoxifen
hormone treatment for breast cancer | signaliing via ERs is inhibited

1st year: Physiology and Metabolism (7 decks)

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