Foundation 2

Question 1

Describe how a membrane potential is related to ion distribution

Answer 1

The distribution of ions (Na+, K+, Cl-, large anions) is different intracellularly to extracellularly. There is high [Na+], [Cl-] outside the cell and high [K+], [A-] inside the cell.
The distribution is such that the resting membrane potential (i.e. the potential across the membrane when nothing is happening) is -70mV. This means that the inside of the cell is 70mV less than the outside at rest.
Ion channels (voltage-gated, ligand and leak) allow the transport of ions across the membrane in response to stimuli or through conc. gradients.

Question 2

Describe how an action potential is generated and propagated along a neurone

Answer 2

A stimulus causes some voltage-gated Na+ channels to open and Na+ to enter the cell, causing an increase in potential from RMP.
Once the membrane potential has reached threshold (-55mV), all the Na+ channels open and Na+ rapidly rushes into the cell (down its conc. gradient). This is depolarisation.
K+ channels start to open and K+ flows out of the cell (down its conc. gradient).
The Na+ channels close but the K+ channels remain open so the membrane potential becomes more negative. This is repolarisation.
The K+ channels are slow to close which means the membrane potential momentarily dips below RMP. This is hyperpolarisation.
Eventually, all the K+ channels close and the Na+/K+ ATPase equalises the membrane potential to RMP.

The AP propagates down the axon via current loops the currently depolarised segment causes the adjacent segment’s voltage gated Na+ channels to open, causing an influx of Na+ eventually reaching threshold, causing the cycle to happen again. Meanwhile, the previously depolarised segment repolarises.

Question 3

Describe how arrival of an action potential at a terminal bouton triggers neurotransmitter release

Answer 3

An AP arriving at the nerve terminal causes voltage-gated Ca2+ channels to open at the presynaptic membrane.
Ca2+ ions rush into the cell down their conc. gradient.
The rise in intracellular Ca2+ causes the vesicles containing neurotransmitter to fuse with the presynaptic membrane and release their contents into the synaptic cleft (exocytosis).

Question 4

Describe myelination in the central and peripheral nervous system

Answer 4

In the peripheral NS, myelin is closely packed layers of Schwann cell membranes wrapped around the axon.
In the central NS, oligodendrocytes form the myelin sheath.

Question 5

Describe the divisions of the nervous system (e.g. brain, spinal cord and peripheral nervous system)

Answer 5

Nervous System –> Central NS and Peripheral NS
Central NS –> Brain and Spinal Cord
Peripheral NS –> Autonomic NS and Somatic NS
Autonomic NS –> Sympathetic NS (fight or flight) and Parasympathetic NS (rest and digest)
Somatic NS = voluntary, muscles

Question 6

Describe the divisions of the nervous system (e.g. brain, spinal cord and peripheral nervous system)

Answer 6

Nervous System –> Central NS and Peripheral NS
Central NS –> Brain and Spinal Cord
Peripheral NS –> Autonomic NS and Somatic NS
Autonomic NS –> Sympathetic NS (fight or flight) and Parasympathetic NS (rest and digest)
Somatic NS = voluntary, muscles

Question 7

Describe the general structure and role of a synapse and the role of the neuromuscular junction as a specialised synapse

Answer 7

The synapse has the axon terminal, presynaptic membrane, vesicles, postsynaptic membrane and the postsynaptic membrane.
The role of the synapse is to allow easy transmission of electrical and then chemical signals to another neurone of the effector cell.
The NMJ is a synapse between a motor neuron and muscle fibre. It allows the motor neuron to transmit information to the muscle fibre, for example contraction.

Question 8

Describe the general structure and role of a synapse and the role of the neuromuscular junction as a specialised synapse

Answer 8

The synapse has the axon terminal, presynaptic membrane, vesicles, postsynaptic membrane (which has junctional folds) and the postsynaptic membrane. There are Ca2+ channels on the presynaptic membrane and transmitter receptors on the postsynaptic membrane depending on the type of neuron.
The role of the synapse is to allow easy transmission of electrical and then chemical signals to another neurone of the effector cell.
The NMJ is a synapse between a motor neuron and muscle fibre. It allows the motor neuron to transmit information to the muscle fibre, for example contraction.

Question 9

Describe the gross anatomy of the brain

Answer 9

(look at a picture)
From a sagittal (side) view:
Front = Anterior/Rostral
Back = Posterior/Caudal
Top = Superior/Dorsal
Bottom = Inferior/Ventral

From a superior (top) view:
Front = Frontal Pole
Back = Occipital Pole
Right and left hemispheres divided by a longitudinal fissure.

Lobes:
Frontal Lobe, Parietal Lobe, Occipital Lobe, Temporal Lobe

Gross brain structures:
Cortex, Gyrus, Sulcus, Cerebellum, Brainstem, Spinal Cord

The brain has grey matter (which is along the outer edge) and white matter (which is on the inside). The white matter contains ventricles and nuclei.

Question 10

Describe the location of cholinergic and adrenergic receptor subtypes and the effects of their activation

Answer 10

Generally:
In the sympathetic and parasympathetic NS, nicotinic receptors are located on the postganglionic fibres (and so are activated by ACh).

Muscarinic receptors are located on the effector organ in the parasympathetic NS (and so are also activated by ACh).

Adrenergic receptors are located on the effector organ in the sympathetic NS (and so are activated by NA).

Exceptions:
Sweat glands are activated by the sympathetic NS, but use ACh as both the pre- and postganglionic transmitters.

Adrenaline release from adrenal glands is mediated by the sympathetic NS - ACh acts on the glands, which release adrenaline into the bloodstream.

Also some neurons release neither ACh or NA - these are called non-adrenergic, non-cholinergic neurons.

Question 11

Describe the major receptor subtypes at synapses

Answer 11

Adrenergic receptors:
alpha 1, alpha 2, beta 1, beta 2

Muscarinic receptors:
M1, M2, M3, M4, M5

Question 12

Describe the processes involved in signal transmission in the CNS

Answer 12

There are 2 modes of neuronal signal transmission:
Electrical - action potentials in the neuron
Chemical - neurotransmission between neurons

Question 13

Describe the relative affinities for norepinephrine and epinephrine of the adrenoceptor subtypes

Answer 13

alpha 1: NA > Adr
alpha 2: NA > Adr
beta 1: NA = Adr
beta 2: Adr > NA

Question 14

Describe the role of myelin in normal neurone

Answer 14

Myelin provides electrical insulation - conduction is faster in myelinated axons (by 100x).
In the gaps between Schwann cells are nodes of Ranvier. Na+ channels are concentrated at the nodes. Myelin allows the action potential current to ‘jump’ from node to node (called saltatory conduction). This is faster than if the current was just travelling along the axon (called smooth conduction)

Question 15

Describe the roles of the sympathetic and parasympathetic divisions of the autonomic nervous system

Answer 15

Sympathetic NS involved in fight or flight responses such as increased heart rate (via B1 and B2), vasoconstriction (via a1), vasodilation (via B2), Adr and NA release (via nicotinic receptors in adrenal medulla) and bronchodilation (via B2 in lungs).

Parasympathetic NS involved in rest and digest responses such as decreased heart rate (via M2), watery secretion from salivary glands (via M3) and bronchoconstriction (via M3 in lungs)

Question 16

Describe the structure of a neurone

Answer 16

There are many different types of neuron but they all tend to have a cell body (soma), dendrites, axon hillock, axon, axon terminal and synapse.

Question 17

Describe the structure of a typical spinal nerve

Answer 17

Look at slides 86 and 87 on intro to neurobiology part 2 for diagram.

They have an epineurium (connective tissue sheath around entire nerve), a fascicle (a bundle of nerve fibres, in this case), perineurium (surrounds each fascicle), endoneurium (lies between each fibre), axon with myelin sheath.

Question 18

List the major neurotransmitters of the CNS

Answer 18

Amino Acids:
Acetylcholine (excitatory or inhibitory), Glutamate (excitatory), gamma-aminobutyric acid (GABA) (inhibitory)

Biogenic Amines:
Dopamine (excitatory via D1, inhibitory via D2), noradrenaline (excitatory), adrenaline (excitatory), Serotonin (5-HT) (excitatory or inhibitory)

Neuropeptides:
Substance P (excitatory), opioids (inhibitory)

Question 19

List the major neurotransmitters of the CNS

Answer 19

Amino Acids:
Acetylcholine (excitatory or inhibitory), Glutamate (excitatory), gamma-aminobutyric acid (GABA) (inhibitory)

Biogenic Amines:
Dopamine (excitatory via D1, inhibitory via D2), noradrenaline (excitatory), adrenaline (excitatory), Serotonin (5-hydroxytryptamine, 5-HT) (excitatory or inhibitory)

Neuropeptides:
Substance P (excitatory), opioids (inhibitory)

Question 20

Define the terms affinity, efficacy and potency

Answer 20

Affinity - how well a ligand binds to a receptor
Efficacy - the ability of a ligand to activate the receptor
Potency - measure of drug activity expressed in terms of the amount required to produce an effect of given intensity (a highly potent drug evokes a response at low concentrations, a low potency drug evokes the same response at a higher concentration)

Question 21

Define the terms agonist, antagonist and partial agonist

Answer 21

Agonists are drugs that bind to a receptor to cause a biological response.
Antagonists are drugs that block the action of an agonist at the receptor.
Partial agonists are drugs that are unable to produce a maximum response even when occupying all available receptor

Question 22

Define phase I and II metabolism

Answer 22

Phase 1 metabolism is catabolic. The reactions involved tend to expose or introduce groups that make a lipophilic drug more hydrophilic for excretion.
Oxidation is the most common phase 1 reaction, other reactions include reduction and hydrolysis.
Several enzymes are involved but the cytochrome P450s are the most important.

Phase 2 metabolism is anabolic. These reactions involve conjugation of the reactive group often introduced in phase 1.
Phase 2 reactions usually lead to inactive and polar substances that are easily excreted.

Question 23

Define the term pharmacodynamics

Answer 23

The effect of a drug on the body - mechanisms of action of drugs, influence of drug concentration on the magnitude of response

Question 24

Define the term therapeutic index

Answer 24

The therapeutic index is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity

TI = TD50/ED50
TD50 = dose of drug that causes a toxic response in 50% of the population
ED50 = dose of drug that is therapeutically effective in 50% of the population

Question 25

Describe first pass metabolism and its importance

Answer 25

When a drug is administered, some is metabolised by metabolizing enzymes in the gut wall.
After absorption, the drug enters the portal system and goes to the liver where it is metabolised.

First pass metabolism is this metabolism that occurs before the drug can have a pharmacological effect in the body.
It is important because it means we might need to give a larger oral dose or use an alternative route of administration.

Question 26

Describe how one drug can influence the absorption of another

Answer 26

One drug might require a certain transporter for it to be absorbed. If another drug uses the same transporter, then it will take longer for that drug (or the first drug) to be absorbed depending on affinities. This is undesirable because one of the drugs will not have a pharmacological effect as quickly as intended.

Question 27

Describe how the physical chemical characteristics of drugs influence their movement across physiological barriers

Answer 27

There are 3 main ways in which drugs cross cell membranes to be absorbed (predominantly occurs in the small intestine):

1. passive diffusion through lipid
2. diffusion through aqueous channel
3. carrier mediated transport

Depending on whether the drug is ionised or unionised will dictate whether the drug can passively diffuse through the lipid membrane.

Drugs that are in the same pH environment that they are (i.e. acidic drug in acidic pH, basic drug in basic environment) will be UNIONISED and therefore CAN passively diffuse through the membrane.

Drugs in a different pH environment (i.e. acidic drug in basic environment, basic drug in acidic environment) will be IONISED and therefore CANNOT passively diffuse through the membrane.

Question 28

Describe the concept of bioavailability in pharmacology

Answer 28

Bioavailability is the proportion of a drug that passes into the systemic circulation after administration

Question 29

Describe the phenomena of desensitisation and tolerance in pharmacology

Answer 29

Tolerance is the reduction in response to a drug after repeated.

2 major types of tolerance exist:

1. Pharmacokinetic (e.g. altered drug metabolism)
2. Pharmacodynamic - desensitisation:
   - Receptor internalisation
   - Receptor down-regulation
   - Decreased activity of intracellular signalling pathways and ion channels

Question 30

Describe the terms drug and medicine and explain the extent of their use within the healthcare system

Answer 30

Drug = a chemical substance, which, when administered to a living organism, produces a biological effect

Medicine = a chemical preparation, which usually contains one or more drugs, administered with the intention of producing a therapeutic effect.
Medicines usually contain other substances (e.g. excipients, stabilisers, solvents) besides the active drug to make them more convenient to use.

See slides 14, 15, 17 for data on extent of medicines used within the healthcare system (NHS)

Question 31

Describe the terms pharmacology, clinical pharmacology and therapeutics

Answer 31

Pharmacology = the study of drugs and their interactions with the body

Clinical pharmacology = all aspects of drug therapy in clinical practice, from basic mechanisms to practical prescribing, to the effects of drug usage in whole populations

Therapeutics: treatment and care of a patient for the purpose of preventing, supressing or curing a disease or alleviating pain or injury.

Question 32

Explain the concepts of drug selectivity and specificity

Answer 32

Many drugs act preferentially on particular receptors or subtypes or receptors - selectivity.

No drug is specific (i.e. 100% selective for only one receptor subtype).

For example, salbutamol is ~10x more effective at stimulating B2 receptors in airways than B1 receptors in the heart, but it will stimulate B1 receptors in the heart at high concentrations

Question 33

Explain the differences between various routes of drug administration

Answer 33

The main differences occur in absorption of drugs.

Orally administered drugs have to be absorbed (mainly in the small intestine) and then enter the plasma. Some of the drug will be excreted without being absorbed.

Whereas, intravenously administered drugs enter the bloodstream straightaway and so can have an immediate effect.

See slide 12 of ‘Drug Absorption and Distribution’ PowerPoint for full table of routes of administration + advantages and disadvantages.

Question 34

Explain the distribution of drugs across body compartments

Answer 34

Drugs diffuse, or are transported, from the plasma into tissues.

Tissues can bind drugs:

• either due to their composition - lipid soluble drugs will accumulate in fat
• via binding to cellular components - proteins, pigments, minerals

Drugs can also be distributed total body water (which are lipid soluble and can readily cross cell membranes), the extracellular compartment (which cannot easily enter cells because of their low lipid solubility), the plasma (which are too large to cross the capillary wall easily).

Question 35

Explain the effect of antagonists on the dose-response curve of an agonist

Answer 35

A competitive antagonist will cause a parallel shift to the right (can be overcome by increasing agonist conc.). It will have the same shape and same maximal response.

Irreversible antagonists will cause the curve to have a reduced maximal response (cannot be overcome by increasing agonist conc.)

Question 36

Explain the four phases of pharmacokinetics

Answer 36

Pharmacokinetics = what the body does to the drug - ADME

Absorption - from site of administration into the blood

Distribution - drug can reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids of tissues

Metabolism - body inactivates the drug through enzymatic modification

Excretion - drug is eliminated from the body in urine, bile or faeces

Question 37

Explain the role of the liver and cytochromes in drug metabolism and clearance

Answer 37

Drug metabolism occurs predominantly in the liver, especially by the cytochrome P450 enzymes.

The CYP enzymes are located in most cells but are primarily found in the liver, they are involved in the metabolism of ~75% of all drugs in use today.

For clearance, the liver produces and secretes bile into small bile ducts, which join together to form the common hepatic duct.
The bile then goes into the gall bladder where it is stored and concentrated for later use.
The conjugate is excreted in the bile into the gut (from the gall bladder) where it is eliminated in the faeces(?).

Question 38

Explain the routes of drug excretion from the body

Answer 38

1. Kidneys (renal excretion)
   - excretion in urine
2. Hepato-biliary system
   - excretion in faeces
3. Lungs
   - used for volatile compounds

Question 39

Explain why drug metabolism is a potential point of interaction between drugs

Answer 39

Some drug metabolising enzymes can be induced or inhibited by different compounds such as other drugs, alcohol, smoking, diet etc.

Enzyme induction is primarily caused by an increase in the synthesis of enzymes (phase 1 and 2).

For example, rifampicin incudes CYP2C19 & CYP2C9, these enzymes metabolise warfarin. So if someone is taking both these drugs together then the warfarin will be metabolised quicker than intended and so will not have its pharmacological effect for long enough (so might need to increase dose).

On the other hand ketoconazole and a component of grapefruit juice inhibits CYP3A4, this enzyme metabolises nifedipine. So the effects of nifedipine will be prolonged, and could lead to unintentional easier overdose which will cause hypotension, lethargy, loss of consciousness.

Question 40

Identify molecular targets for drug action including receptors, ion channels, enzymes and transporters

Answer 40

1. Receptors
   - Agonists activate the receptor
   - Antagonists block the action of agonists
2. Ion channels
   - Either block or modulate the opening/closing of channel
   - e.g. benzodiazepine on GABA(A) receptor
3. Enzymes
   - Either inhibit or act as a false substrate
   - e.g. NSAIDs on cyclooxygenase (COX)
4. Carriers (transporters)
   - Either transported in the place of the endogenous substrate or inhibit transport
   - e.g. SSRIs stop serotonin from being taken back up into the neuron, thereby increasing its effect

Question 41

Identify the factors influencing variability in response to drugs

Answer 41

Internal

• Disease state
• Age
• Genetics

External

• Drug formulation
• Drug interaction
• Smoking/alcohol
• Diet and environment

Question 42

Describe basic anatomical terms, structure and concepts

Answer 42

Anatomical position

• Face forward
• Hands by sides, palms forward
• Feet together, toes forward

Terms

• Superior = towards the head
• Inferior= towards the feet
• Anterior/Ventral = towards the front
• Posterior/Dorsal = towards the back
• Superficial = situated at or close to a surface
• Deep = further away from the surface
• Medial = towards the midline
• Lateral = away from the midline
• Distal = away from the origin of a limb or from the median line of the body
• Proximal = close to the origin of a limb or close to the median line of the body
• Prone = face down
• Supine = face up

Planes

• Sagittal = bisects the body into the right and left. If it bisects into 2 equal halves, then it is the median plane. Anything parallel to the median plane is para-sagittal.
• Coronal = at a right angle to sagittal plane, bisects body into anterior and posterior
• Transverse/Horizontal = bisects body into superior and inferior

Question 43

Define hormones and the endocrine system

Answer 43

A chemical/protein synthesised by specific endocrine tissues and secreted into the bloodstream, whereby it is carried to non-adjacent sites in the body and exerts its actions.

The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs.

Question 44

Describe how the actions of steroid hormones are mediated via receptors

Answer 44

1. Since steroid hormones are lipophilic, they can passively diffuse through the membrane and bind to the intracellular receptor.
2. The receptor-hormone complex translocate to the nucleus and bind to DNA response elements within promoter regions of DNA.
3. This recruits RNA polymerase, which leads to the generation of mRNA, which is translated into a protein.
4. The action of the hormone is mediated by the newly-synthesised protein.

Question 45

Describe the different classes of hormones and how they work

Answer 45

Steroid Hormones

• Synthesised from cholesterol (therefore lipophilic).
• Bind to intracellular receptors (because lipophilic).
• Lead to transcription of mRNA that will lead to production of a protein which will mediate the effect of the hormone.

Non-Steroid Hormones

• Polypeptides or modified amino acids (are hydrophilic).
• Bind to cell surface receptors (e.g. GPCRs, tyrosine kinase) which cause a second messenger cascade.

Question 46

Describe the different ways in which cells communicate, e.g. autocrine, paracrine, synaptic and endocrine

Answer 46

Endocrine - cell signals to a distant cell via a chemical messenger released into the circulatory system
Paracrine - cell communicates to the cell(s) next to it
Autocrine - cell signals to itself (e.g. cytokines)
Neurocrine/Synaptic - a neuron signals to a cell using neurotransmitters (really just a special type of paracrine signalling)

Question 47

Describe the hormone receptor system, second messengers and activation of target cell transducer systems

Answer 47

1. Non-steroid hormones cannot diffuse across cell membrane.
2. So hormone binds to a cell surface receptor such as a GPCR or tyrosine kinase.

GPCR
3. Binding causes release of second messengers within the cell.

4. Second messengers activate enzyme cascade.
5. Cascade triggers cellular responses.

Tyrosine Kinase
3. Receptor undergoes autophosphorylation.

4. The phosphorylated tyrosine residues can bind to specific relay proteins which will trigger cellular responses (often via signal transduction pathways).

Question 48

Describe the mechanisms regulating hormone release, activation and feedback control

Answer 48

For example, in the HPA axis, the production of cortisol and adrenaline is going to affect cellular metabolism (mainly increased glucose).

If we don’t use this excess glucose, then we need to turn the pathway off (so blood glucose levels don’t get too high).

This is done via negative feedback: rising levels of cortisol will be sensed by the hypothalamus and anterior pituitary gland to cause a reduction in the release of CRH and ACTH.

Other examples include water levels/blood volume control via antidiuretic hormone and glucose level regulation via insulin and glucagon.

Question 49

Describe the structure and function of the adrenal gland and its hormone products in health and disease

Answer 49

The adrenal glands are made up of 2 parts: adrenal cortex and adrenal medulla. There is a capsule which surrounds them.

The medulla is controlled by sympathetic NS.
The cortex is regulated by adrenocorticotropic hormone and it makes up ~90% of adrenal gland weight.

The adrenal cortex can be divided into 3 zones: glomerulosa (outermost), fasciculata (middle) and reticularis (innermost).
The zona glomerulosa secretes mineralocorticoids (mainly aldosterone).
The zona fasciculata secretes glucocorticoids (mainly cortisol).
The zona reticularis secretes an androgen precursor called DHEA and glucocorticoids as well.

The adrenal medulla is made up of 2 types of neuroendocrine cells: the noradrenaline (NA)-secreting cells and the adrenaline (Adr)-secreting cells which secrete NA and Adr respectively.
These catecholamines are stored in neuroendocrine granules and released in the fight or flight response associated with sympathetic stimulation.

Disease
Increased aldosterone secretion occurs in Conn’s syndrome (rare) and more commonly as a secondary effect of excess diuretic medication or other disorders. It leads to water retention and hypertension.

Increased cortisol secretion leads to Cushing’s syndrome. This is caused by a tumour (would be called Cushing’s disease) or as a secondary effect of excess medication.

A decrease in both aldosterone and cortisol would result from adrenal cortex insufficiency.
This is caused by either destruction of the adrenal gland (Addison’s disease) or upstream disorders of the hypothalamus or pituitary gland.

Question 50

Describe the structure and function of the hypothalamic-pituitary axis and its hormone products in health and disease

Answer 50

The hypothalamus secretes many -releasing or -inhibiting hormones such as thyrotropin-releasing hormone (TRH) or growth hormone-inhibiting hormone (GHIH; somatostatin).

These hormones secreted by the hypothalamus control the release of anterior pituitary hormones. For example, thyroid-stimulating hormone is stimulated by TRH, growth hormone is inhibited by GHIH.

The posterior pituitary hormones are produced in the hypothalamus and stored in the posterior pituitary prior to release. There are 2 hormones stored in posterior pituitary: oxytocin and antidiuretic hormone (ADH).

Disease
Excess growth hormone from the pituitary gland can cause acromegaly or giantism.
Growth hormone deficiency can cause dwarfism (although GH deficiency is not the main cause).

• Cranial diabetes is caused by a lack of ADH production by the hypothalamus (which can be caused by a brain tumour or head injury).
• Kallmann syndrome is a genetic disorder caused by a lack of gonadotropin-releasing hormone (GnRH) by the hypothalamus.

Question 51

Describe the synthesis and release of steroid hormones

Answer 51

Synthesis

• Synthesised from cholesterol in a series of reactions in the mitochondria and smooth endoplasmic reticulum. The cholesterol can either come from our diet or be made in the cell.
• The hormones differ in the side chains attached to the cholesterol rings and the C-C bonding within those rings (i.e. C-C or C=C).
• The synthesis is mainly 2 steps :
  1. Cholesterol is converted to pregnenolone via the enzyme desmolase.
  2. Pregnenolone is converted to progesterone by enzymes in the mitochondria and cytoplasm
• The next steps in the process are quite variable but generally, progesterone is converted into androgens (e.g. testosterone), glucocorticoids (e.g. cortisol) and mineralocorticoids (e.g. aldosterone).
• Androgens can be further converted into oestrogens.

Release

• Steroid hormones are released as soon as they are made because they can diffuse out the cell (because lipophilic), i.e. their rate of release is being determined by their rate of synthesis.
• The steroid hormone-releasing cells all tend to have a lot of mitochondria, SER, small nucleus and a lot of lipid droplets which contain cholesterol. They tend to be situated near blood capillaries so that the steroid hormone can easily be released into the bloodstream.
• Since they are lipophilic and hydrophobic, they need to bind to plasma proteins to be transported in the blood.

Question 52

Describe the synthesis, storage and release of peptides and amino acid hormones

Answer 52

Polypeptide Hormones

• The synthesis of peptide hormones is the same as the synthesis of any protein - it occurs via the process of transcription and translation.
• They are stored in secretory vesicles because they are hydrophilic (so they cannot diffuse out the cell passively).
• These vesicles can be released quickly via exocytosis.

Modified Amino Acid Hormones

• Synthesised from a tyrosine or tryptophan precursor.
• In the case of the catecholamines, they are synthesised from tyrosine, whereas serotonin and melatonin are synthesised from tryptophan.
• The catecholamines are stored in secretory vesicles and released via exocytosis.
• Thyroid hormones are an exception - they are synthesised from tyrosine, but they are iodinated prior to storage in the colloid space (centre of thyroid gland). They are stored as precursors.
• This process of iodination makes them lipophilic which makes them act more like steroid hormones.