Signalling pathways/molecules Flashcards by Olivia Clist

What is physiology?

Energy interacting with matter in living systems

Normal function of living organisms and their parts

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What is the aim of all living systems?

To maximise dynamic order through regulating flow (requires energy).

(Minimise disorder - entropy)

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What governs flow at the cellular level?

Specific temperature range
Molecular/ion type
Ph range
Substrates

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What is pharmacology?

Study of the effect of molecules on physiological and biochemical activity of cells up through to the level of the person

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What are endogenous signalling molecules?

Produced inside the body

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What are exogenous signalling molecules?

Made outside the body. May be:

plant based (natural) e.g. Morphine, antibiotics, aspirin
synthetic (man made) - many

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What is homeostasis?

Maintaining the optimal environment for cells to function

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What is the sequence of negative feedback?

Imbalance - sensor - set point comparator - controller - effector - correction signal

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What is a synergistic feedback loop?

Signals work together to amplify the result

E.g. Temperature control mechanisms work together to reduce/increase temperature

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What is an antagonistic feedback loop?

Often called “push-pull” - where the increasing activity of one effector is accompanied by decreasing activity of an antagonistic effector

E.g. Glucagon and insulin
Adrenaline signal

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What is normal body temperature?

Set point 37 degrees (+/- 1 degree)

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What is the controller of temperature regulation in the body?

Hypothalamus - temperature centre - drives heat loss/gain response

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What is responsible for detecting changes in temperature?

Peripheral temperature sensors in the skin e.g. TRP M8 cold receptor and TRP V4/V3 warm receptors

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What are some features of the heat response?

Peripheral vessels dilate

Sweat glands activated

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What are some of the mechanisms for the heat loss response?

Vasoconstriction (peripheral vessels constrict)
Muscles produce heat by shivering
thyroid gland releases hormones to increase metabolism - increases energy and heat production.

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What temperature is considered hypothermia?

Less than 35 degrees

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At what temperature is thermoregulation lost?

Above ~ 42 degrees

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What are endocrine signalling molecules?

Produced by ductless glands
Secrete hormones into the bloodstream
Typically act over long distances

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What is the potency of hormones?

Highly potent (picomolar 10^-12 M to nanomolar 10^-9 M)

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What are the three major types of hormone?

Amine
Peptide/protein
Steroid

What are amine hormones?

Amino acid derivatives - small charges, hydrophilic
Receptor in the plasma membrane, caused change in membrane potential which triggers synthesis of cytosolic second messengers
Plasma half life - seconds

Give examples of amine hormones

Adrenaline
Noradrenaline
Thyroxine

What are peptide hormones?

Can be short chain - very long (200+aa), hydrophilic.
Receptor in plasma membrane, triggers synthesis of cytosolic second messengers and protein kinase activity
Plasma half life - minutes

Give examples of peptide hormone

Insulin
Glucagon
ANP/BNP

What are steroid hormones?

Derived from cholesterol - lipophilic (hydrophobic) Intracellular receptors (cytosolic or nuclear), receptor-hormone complex controls transcription and stability of mRNA Plasma half life - hours

Give examples of steroid hormone

Testosterone Progesterone Oestrogen

What is paracrine signalling?

Signalling to adjacent cells (short distance)

The synapse is an example of paracrine signalling. Discuss the signalling molecules.

Neurotransmitters Tight coupling of signalling molecule transmission, one direction. Electrochemical to chemical signal conversion. Very fast - msecs

What are the three major types of neurotransmitters?

Amino acids Monoamines Peptides

Give examples of monoamine neurotransmitters

Adrenaline - excitatory Noradrenaline - excitatory Dopamine - excitatory and inhibitory Serotonin - excitatory

Give examples of amino acid neurotransmitters

Glutamate - excitatory Glycine - mainly inhibitory GABA - inhibitory

Give examples of peptide neurotransmitters

Opioid peptides

What is a notable exception to the major groupings of neurotransmitters

Acetyl Choline - excitatory

Paracrine signalling molecules also include local chemical mediators such as...

Interleukins Chemokines Interferons Cytokines

What is autocrine signalling?

Cells respond to signalling molecules they produce/release themselves

What is a receptor?

Any molecule for which there is an interaction which has a known/putative physiological or therapeutic effect

What are the main signalling molecule targets?

R - receptors I - ion channels T - transporters E - enzymes

What are important exceptions to the RITE signalling molecule targets?

Chemotherapy a target is structural protein/DNA | Antibiotics - selectively targets bacteria (another organism)

What are the four main groups of receptors?

K - kinase linked receptor e.g. Cytokine receptors I - ion channels (ligand gated) e.g nicotinic Ach receptors N - nuclear/intracellular e.g oestrogen receptors G - gpcr e.g. Muscularinic Ach receptors

What are kinase linked receptors?

Wide variety of ligands (hormones, growth factors, cytokines) Act via phosphorylation of serine/threonine/tyrosine and starts a signalling cascade

What are ligand gated ion channels?

Also called ionotropic receptors When ligand binds, conformational change causes opening/closing of ion channel. May be very fast e.g. Neurotransmitters

What are nuclear/intracellular receptors?

For lipid soluble ligands such as steroids When ligand-receptor complex migrates to nucleus, binds to transcription factor, activates/inactivated a gene or set of genes

What is the function of ion channels?

Selectively allow ions (Na, K, Ca, Cl) to cross plasma membrane down electrochemical gradient Also regulate voltage signals in excitable cells - maintain membrane potential

What are transporters/carriers?

Act in facilitated diffusion - transport ions/small molecules into/out of cells May use ATP (against gradient) or preexisting ion gradient (symport and antiport)

During exercise heart and lung function changes to meet demand in what ways?

Supply more oxygen from lungs to muscles And more glucose to muscle Remove CO2 and h2o from respiration in muscle (to lungs) Increase rate of heat loss (via capillary heat exchange network)

What Happens to proteins above 40 degrees?

Loss of structure - braking of covalent and electrostatic forces

What things might you do in practice to deal with hyperthermia?

Remove layers Open windows Paracetamol Increase fluids

What things might you do in practice to deal with hypothermia?

Add layers Bear hugger blankets IV fluids

Why might elderly people be more susceptible to hypothermia?

Natural degeneration of muscle/fat body mass - less able to generate heat, poorer thermoregulation May also be diabetic - diabetic neuropathy causing less response to cold sensation Socially - poorer diet, less movement, no heating in home