Different types of signalling molecules

Signalling molecules are either…

hydrophobic or hydrophilic

State 3 properties of hydrophilic signalling molecules

• soluble in aqueous solutions

• can travel directly in blood, extracellular fluid, or lymph

• require a membrane bound receptor

State 3 properties of hydrophobic signalling molecules

• insoluble in aqueous solution

• require solubilisation by binding to a transport protein

• target intracellular (nuclear receptors)

List the 6 classifications of signalling molecules

• peptides

• amines

• steroids

• lipids

• purines

• gasses

Which signalling molecules are strictly hydrophobic?

steroids and lipids

Which signalling molecules are strictly hydrophilic?

• peptides

• purines

• gasses

Which signalling molecule can be hydrophilic or hydrophobic?

amines

What can peptides and amino acids function as?

neurotransmitters

List 3 amino acids that can function as neurotransmitters

• cysteine

• aspartic acid

• glutamic acid

List two true peptide messengers

• adrenaline

• oxytocin

Sending out peptide ligands

signal is packaged into secretory vesicles so they can be released into the extracellular space via exocytosis

Give an example of a peptide ligand that can be released immediately after synthesis

cytokines

Give 2 examples of a peptide ligand that can be stored and only released when required

peptide hormones and neurotransmitters

State the two broad types of peptide receptors

ionotropic and metabotropic receptors

Ionotropic receptors

binding of signal to receptor results in change of ion flux within cell

Metabotropic receptor

binding of signal to receptor results in a change of enzyme activity within a cell

How is the signal stopped from continually activating the receptor once bound?

protease/peptidase enzymes are present to degrade the signal

Would it take a glycoprotein signal more or less time to be degraded?

more time

Define a biogenic amine

naturally occurring organic compounds with an amine group

List 5 biogenic amines

• catecholamines

• thyroxine

• indoleamines

• histamine

• acetylcholine

Give 3 examples of catecholamines

• dopamine

• adrenaline

• noradrenaline

What amino acid are catecholamines derived from?

tyrosine

Are catecholamines hydrophilic or hydrophobic?

hydrophilic

What amino acid is thyroxine derived from?

tyrosine

Is thyroxine hydrophilic or hydrophobic?

hydrophobic

What does binding of thyroxine facilitate?

increase of basal metabolic rate

Give 2 examples of indoleamines

• serotonin

• melatonin

What amino acid are indoleamines derived from?

tryptophan

Are indoleamines hydrophilic or hydrophobic?

hydrophilic

What amino acid are histamines derived from?

histidine

Are histamines hydrophilic or hydrophobic?

hydrophilic

What do histamines trigger in vascular tissue?

vasodilation

What do histamines trigger in the bronchus?

bronchoconstriction

What can histamines also act as?

a chemoattractant for mast cells

What amino acid is acetylcholine derived from?

choline

Is acetylcholine hydrophilic or hydrophobic?

hydrophilic

Are nicotinic acetylcholine receptors ionotropic or metabotropic?

ionotropic

What are all steroids derived from?

27 carbon cholesterol

List the 3 things steroids can act as

• endocrine hormones

• paracrine hormones

• pheremones

List the 5 classes of steroid hormones

• progestins

• glucocorticoids

• mineralocorticoids

• androgens

• estrogens

Give an example of a progestin

progesterone

Give an example of a glucocorticoid

cortisol

Give an example of a mineralocorticoid

aldosterone

Give an example of an androgen

testosterone

Give an example of an estrogen

estradiol

Where are all steroid hormones synthesised?

mitochondrial and SER of glands

Can steroid hormones be stored in a cell?

no they must be secreted immediately from cell

How is the binding of steroid hormones to carrier proteins regulated?

by the laws of mass action and mass action equilibrium (M+C ←> MC)

What is the most important type of lipid?

eicosanoids

Give 3 examples of eicosanoids

• prostaglandins (PG’s)

• thromboxanes (TX’s)

• leukotrienes (LT’s)

What are prostoglandins and thromboxanes synthesised by?

cyclooxygenase (COX) and prostaglandin synthase (PTGS) enzymes

What are leukotrienes synthesised by?

lipoxygenase enzymes

Which two lipid messengers are important mediators in the inflammatory cascade?

prostoglandins and leukotrienes

What is the lipid substrate for cyclooxygenase and lipoxygenase?

arachidonic acid

How is arachidonic acid strored?

esterified to glycerol in membrane phospholipids

How is arachidonic acid modified to then produce cyclooxygenase and lipoxygenase?

hydrolysis of ester bond by phospholipase A₂ (PLA₂)

State two methods in order to limit inflammation / relieve pain

• inhibit PLA₂ via anti-inflammatory sterioids

• inhibit downstream cyclooxygenase and lipoxygenase synthase enzymes via non-steroid anti-inflammatory drugs

Give two examples of anti-inflammatory nsterioids

• cortisol

• synthetic glucocorticoids (hydrocortisone)

Give 3 examples of non-steroid anti-inflammatory drugs

• asprin

• paracetamol

• ibuprofen

What does PGF_2α do?

induces contraction of smooth muscle

What does PGE₂ do?

acts as a vasodilator

What is prostoglandin function reliant on?

hydroxyl group within its structure

What are prostoglandins inactivated by?

short-chain alcohol dehydrogenase enzymes

State the two purines

adenine and guanine

State the two forms that purine ligands can exist as

• nucleosides

• nucleotides

List the two nucleosides

adenosine and guanosine

List 3 purine nucleotide variants

• AMP

• ATP

• GTP

List 4 things that purine ligands can act as

• neurotransmitters

• neuromodulators

• autocrine hormones

• paracrine hormones

What is the function of a neuromodulator

modulates neuronal response to neurotransmitters

What can hydrolyse purine ligands?

endonucleotidase enzymes

State two paths purine ligands can act via

• metabotropic GPCRs

• ionotropic receptors

What ions do ionotropic purine receptors mediate?

Na⁺, K⁺, Ca²⁺

List 3 examples of gasses acting as ligands

• carbon monoxide (CO)

• hydrogen sulfide (HS)

• nitric oxide (NO)

What proteins to gas ligands bind to?

intracellular proteins

Why do gas ligands bind to intracellular proteins despite being hydrophilic?

gas ligands are small and so can diffuse freely through the plasma membrane

What is nitrous oxide dervived from and by which enzymes?

L-arganine by NO synthase enzymes

Why can NO only act in auto/paracrine manners?

they have a very short half life (2-30 seconds)

List two things nitrous oxide can act as

• paracrine signal = immune system

• vasodilator

How does nitrous oxide act as a vasodilator? (2 points)

diffuses into vascular smooth muscle cells and binds to guanylyl cyclase

• converts GTP into cGMP, this then activates protein kinase G to relax the smooth muscle layer