L2 - Peptide and Steroid Hormones

Question 1

Peptide Hormone Formation & Secretion (3)

Answer 1

1. Synthesised on ribosomes (on RER)
   o SS binds SRP - SS-SRP complex binds to receptor in RER membrane - peptide transported into RER lumen
   - SS cleaved off - further processing (e.g. glycosylation)
2. Formation of transport vesicles to transfer peptide to Golgi (modification, Sorting and packaging, Filtering imperfectly synthesised proteins)
3. Secretion (exocytosis): 2-step process
   o Secretory granules translocation to plasma membrane – involves cytoskeleton: MF’s and MTs)
   o Docking and fusion of SG with PM – involves docking (fusion proteins:SNARE hypothesis)

Question 2

Peptide Hormone Secretion often..?

Answer 2

Biphasic

Question 3

Peptide Hormone Action (transport and receptor domains and pathway)

Answer 3

Transported via circulation (aqueous)

Receptor (affinity and specificty) - 3 functional domains
o	Extracellular (binding)
o	1-7 membrane-spanning domains (hydrophobic amino acids) – “hydropathy plot”
o	Intracellular (effector’ function)

• Hormone binding > conformational change in receptor, relayed to effector > generation of intracellular signals (2nd messengers) > cellular response (stimulatory OR inhibitory)

Question 4

Adenylate cyclase / cyclic AMP system

Answer 4

GS – receptors attached here are stimulatory adenylyl cyclase – Cyclic AMP (signaling molecule)

GI – Inhibitory – to adenylyl cyclase – lower cAMP why? = Complex e.g. fight or flight when safe we need to be able to stop response.

Question 5

Calcium-mobilising receptors

Answer 5

Cytosolic [Ca2+] is maintained at low levels (typically 10-7M) - 1.3mM outside

By plasma membrane & smooth ER calcium ATP-ases (PMCA – out (keeps levels low in cell) & SERCA – back into ER from cytosol?)

Question 6

By Ca2+ entry from extracellular fluid

Answer 6

Via membrane Ca2+ channels

Receptor-operated Ca2+ channels (ROCCs): e.g. H1 histamine receptor

Voltage-sensitive Ca2+ channels

Question 7

Ca2+ mobilisation from the SER: Inositol lipid signalling

Answer 7

IP3 cleaves off goes to receptor on ER > release calcium -= Calcium and DAG = activate PKC

Question 8

Tyrosine kinase couples receptors (e.g. insulin receptors) (AA, pathway, structure and alpha/beta subunits)

Answer 8

AA tyrosine can be phosphorylated

Hormone binding > activation of tyrosine kinase > phosphorylation of target proteins specifically on tyrosine residues > ‘cascade’ of protein phosphorylation > cellular response

Span membrane once but work in couple – dimerise on activation and transphosphorylate each other – and further phosphorylate other

Alpha (extra): binding / Beta (intra): ATP-binding and tyrosine kinase domains

Question 9

Steroid Hormones (2 conversions, solubility, action and synthesis)

Answer 9

Cholesterol → Cortisol

7-dehydro cholesterol break double bond → Vitmain D3

Insoluble in blood serum: Must be carried i.e. protein bound.
• Enters cell easily → intracellular effects (lipophobic)
• Steroid hormone synthesis: adrenals, gonads and placenta(peripheral tissues to lesser extent)
Cannot store steroids.

Expression of specific genes altered

Question 10

GPCR Ligands – Polypeptides / Modified Amino Acids

Answer 10

tyrosine
dopamine
noradrenaline
adrenaline

Question 11

Phosphrylation of which aa?

Answer 11

Serine/Threonine and Tyrosine

-OH group

easterfication