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WEEK 1 Flashcards

1
Q

What are the three main types of cell communication?

A

Autocrine, Paracrine and Endocrine signalling

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2
Q

What is autocrine signalling?

A

Secretory cell=target cell (intracrine=same but acts within same cell rather than binding to cell’s target sites)

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3
Q

What is paracrine signalling?

A

Secretory cell adjacent to target cell

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4
Q

What is endocrine signalling?

A

Substance secreted into general circulation and reaches target cell at a distance

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5
Q

What are the nicotinic effects of ACh?

A

muscle contraction, synaptic transmission (autonomic ganglia, parasympathetic postganglionic, CNS)

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6
Q

What are the receptors that cause nicotinic effects of ACh?

A

nAChRs (ion channels)

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7
Q

What are the muscarinic effects of ACh?

A

bradycardia, salivation, bronchospasm, mydriasis

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8
Q

What are the receptors that cause muscarinic effects of ACh?

A

M1-5 (GPCRs)

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9
Q

How do you measure ligand binding to a receptor?

A

Radioactive binding assay

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10
Q

Describe the process of radioactive binding assay

A

add radioactive ligand to sample containing receptor, wash, measure radioactivity

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11
Q

What is the equation for fraction of occupancy?

A

[Radioactive ligand]/[Receptor(total)]=[L]/[L]+Kd

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12
Q

What is the equilibrium dissociation constant (Kd) and what does it measure?

A

concentration of ligand where 50% of receptors are occupied by ligand=ligand affinity

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13
Q

What are the four main receptor types?

A

Ligand-gated ion channels (ionotropic)-eg. nAChRs
G-protein coupled receptors (metabotropic)-eg. mAChRs
Kinase-linked receptors-eg. cytosine receptors
Nuclear receptors-eg. oestrogen receptor

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14
Q

Process of GPCRs

A

Receptor in plasma membrane is bound by agonist, causes change in receptor conformation, activation, heterotrimeric G protein consistent of alpha, beta and gamma protein reassembles, active G protein receptors interact with G protein bound to plasma membrane by lipid anchors, G protein coupling, alpha, beta and gamma subunits dissociate causing nucleotide exchange-GDP moves off, GTP replaces it, activated G protein subunits regulate effector proteins, beta-gamma dimer formed which activates Ca2+ ion channels, GTP hydrolysis causes inactivation of Galpha protein

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15
Q

What effect does the Gs alpha subunit cause?

A

ATP-(adenylyl cyclase)->cAMP-(cAMP phosphodiesterase (PDE))->AMP

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16
Q

What effect does the Gq alpha subunit cause?

A

Gq->Phospholipase C->diacylglycerol-activates Protein Kinase C by binding of InsP3 to channels on ER surface, causing Ca2+ to move out and cause biological response

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17
Q

Describe the process of hormonal regulation of glycogen metabolism

A

Gs->AC->cAMP->Protein Kinase A
Protein Kinase A causes: Glycogen synthase phosphorylation (inactivation), Phosphorylase kinase phosphorylation (activation) which causes glycogen phosphorylase b to form glycogen phosphorylase a which causes glycogen hydrolysis in the liver

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18
Q

What is the role of Protein kinase?

A

Protein phosphorylation

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19
Q

What is the role of Protein phosphatase?

A

Protein dephosphorylation

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20
Q

TSH receptor signalling in the Thyroid with relation to the cAMP/PKA pathway

A

TSH binds to TSHR, causes Gs alpha subunit to activate adenylyl cyclase which forms cAMP from ATP, which activates Protein Kinase A (PKA), causing transcription of genes that form Tg-1, from which T3 and T4 are formed

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21
Q

What is an autonomous thyroid adenoma (ATA)?

A

benign tumour in the thyroid gland which causes hyperthyroidism-60% of cases due to activating TSHR mutation

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22
Q

What do homozygous muts suffer from and why?

A

Severe congenital hypothyroidism due to inactivating TSHR mutations

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23
Q

What do heterozygous muts suffer from and why?

A

Mild/compensated hypothyroidism due to inactivating TSHR mutations

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24
Q

What is the effect of positive feedback loops?

A

Stimulatory

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25
What is the effect of negative feedback loops?
Inhibitory
26
What is a hormone?
A substance secreted directly into the blood by specialised cells which is present in minute concentrations and binds to specific receptors on target cells
27
What is homeostasis?
The maintenance of a constant internal environment
28
Describe the endocrine feedback loop
Stimulus activates Gland A which produces Hormone A, which activates Gland B/target tissue which activates Hormone B which causes action. Hormone B also causes inhibition of Gland A and Hormone A.
29
What are the two types of hormones?
Lipophilic (steroid hormones) and Water-soluble (peptide hormones)
30
What is a lipophilic (steroid) hormone?
A substance able to pass through the phospholipid bilayer and bind to receptors in the target cell
31
What is a water-soluble/hydrophilic (peptide) hormone?
A substance unable to pass through the membrane so binds to a receptor on the cell surface and causes conformational change which mediates effects into the cytoplasmic side via secondary messengers
32
How are hormones regulated?
``` Biosynthesis Secretion Circulation/distribution Peripheral modification Receptor interaction Hormone metabolism/excretion ```
33
What are the basic actions of the thyroid hormones?
basal metabolic rate, growth
34
What is the basic action of the parathyroid hormone?
Ca2+ regulation
35
What are the basic actions of cortisol?
glucose regulation, inflammation
36
What are the basic actions of aldosterone?
BP, Na+ regulation
37
What are the basic actions of catecholamines?
BP, stress
38
What are the basic actions of oestradiol?
Menstruation, femininity
39
What are the basic actions of testosterone?
Sexual function, masculinity
40
What are the basic actions of insulin?
Glucose regulation
41
What is the basic action of ANP?
Na+ regulation
42
What is the basic action of Vitamin D?
Ca2+ regulation
43
What is the basic action of ACTH?
Adrenal cortex regulation
44
What is the basic action of TSH?
Thyroid hormone regulation
45
What are the basic actions of GH?
Growth, metabolism regulation
46
What are the basic actions of LH/FSH?
Reproductive control
47
What is the basic action of Prolactin?
Breast milk production
48
What is the basic action of ADH?
Water regulation
49
What is the basic action of Oxytocin?
Breast milk expression (lactation)
50
What is the result of binding of an auto-antibody to TSH receptors?
stimulation of unregulated hyper-production of thyroid hormones with no negative feedback to pituitary gland to secrete less TSH
51
What is the general management strategy for hormone excess?
Remove/block
52
What is the general management strategy for hormone deficiency?
Replace
53
What are three types of glands?
Endocrine, exocrine and mixed glands
54
What are endocrine glands?
Ductless glands that release secretions (hormones) into the blood directly from cells
55
What are exocrine glands?
Glands that release their secretions outside the body and may be ducted
56
What are mixed glands?
Glands that can act as endocrine and exocrine glands
57
What are the four characteristic differences between the two major regulatory systems of the body (endocrine and nervous systems)?
Many hormones vs. few neurotransmitters Generally slow vs. generally rapid Generally long-lasting vs. generally short-lived Widespread-in blood vs. localised-cell to cell
58
What are the different mechanisms of chemical signalling?
Neuroendocrine, endocrine, paracrine, autocrine and intracrine.
59
What is feedback?
Process by which body senses change and responds to it
60
What is negative feedback?
Process by which body senses change and activates mechanism to reduce it (inhibits hormone release in endocrine cascade)
61
What is positive feedback?
Process by which body senses change and activates mechanism to amplify it (stimulates hormone release in endocrine cascade)
62
Process of peptide hormone synthesis, packaging and release
1 ) mRNA on ribosomes binds AA into peptide chain called preprohormone, chain is directed into the ER lumen by a signal sequence of AA 2) enzymes in the ER chop off signal sequence creating inactive prohormone which passes from the ER through the Golgi complex 3) secretory vesicles containing enzymes and prohormone bud off the golgi and enzymes chop the prohormone into one or more active peptides plus additional peptide fragments 4) secretory vesicles release the contents by exocytosis into the extracellular space 5) hormone moves into circulation for transport to target
63
Where are steroid hormones synthesised?
Adrenal gland
64
Describe the storage and transport of steroid hormones
Not stored but synthesised in cytosol as required, then diffuse out of the cell and transported as lipoprotein
65
Process of steroid hormone synthesis
1) hydrolysis of esters and release of cholesterol from the cell membrane 2) cholesterol to pregnenolone in mitochondria 3) processing of pregnenolone to necessary hormone via cell-specific enzymes in SER 4) egress by diffusion/facilitated diffusion
66
What regulates the movement of cholesterol to mitochondrion?
Steroid acute regulatory protein (stAR)
67
What regulates steroid acute regulatory protein (stAR) activity and cholesterol processing?
ACTH
68
How is aldosterone formed in the zona glomerulosa but not the other adrenocortical regions?
Zona glomerulosa contains cells expressing enzymes leading to aldosterone synthesis which are not present in the other regions
69
What are amine hormones?
Thyroid hormones->small, non-polar molecules-therefore hydrophobic and lipophilic
70
What is the difference in the number of iodine atoms in thyoxine/tetraiodothyronine (T4) and triiodothyronine(T3)?
T4=4 iodine atoms | T3=3 iodine atoms
71
Which hormones require carrier proteins?
Steroid and thyroid hormones
72
What is the effect of hormone carrier proteins?
Increase solubility Increase half-life Reservoir in blood
73
What are the two types of carrier proteins?
Specific binding proteins (eg. thyroid binding globulin (TBG) and cortisol binding globulin (CBG)) Non-specific binding proteins (eg. albumin-loose binding->binds aldosterone)
74
What is the site of action of hormones?
Protein/peptide=cell surface receptors | Steroid=intracellular receptors in cytoplasm/nucleus-hormone-receptor complex binds to HRE (hormone response element)

CEP (9 decks)

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