Cell Physiology

Question 1

Explain signal transduction.

Answer 1

RECEPTION - TRANSDUCTION - AMPLIFY - RESPONSE

An extracellular first messenger signal molecule activates a receptor which activates intracellular second messenger molecules to be transduced via a specific pathway, to activate a cellular response.

Question 2

Enzyme-linked receptors general mechanism.

Answer 2

• Ligand binding
• Protein conformational change
• Transmitted via TM helix
• Activation of intrinsic enzymes
• Signalling cascade.

Question 3

Enzyme-linked receptor guanylyl cyclase

Answer 3

2 guanylyl cyclase domains convert GTP -> cGMP which activates downstream kinases.

Question 4

Enzyme-linked receptor serine/threonine kinase.

Answer 4

Ser-Threo kinase domains phosphorylate target proteins,

Question 5

Enzyme-linked receptor tyrosine-kinase

Answer 5

Tyr kinase domains phosphorylate self or other proteins

Question 6

Tyrosine kinase-association enzyme-linked receptor

Answer 6

NO KINASE DOMAINS.

Tyr kinase proteins associated non-covalently with cytoplasmic domains.

Question 7

Enzyme-linked receptor tyrosine phosphatase

Answer 7

Receptor contains tyrosine phosphatase domains & dephosphorylate target proteins.

Question 8

What are cell surface receptors.

Answer 8

Hydrophilic signalling molecules activate intracellular signal transduction pathways.

Question 9

What are nuclear (intracellular receptor).

Answer 9

Hydrophobic signalling molecules act as TRANSCRIPTION FACTORS in nucleus to regulate GENE TRANSCRIPTION.

Question 10

Compare steroid and non-steroid hormones (as first messengers)

Answer 10

Steroid:

• lipid soluble (derived from cholesterol)
• small; pass through plasma membrane to bind to intracellular receptors & activate genes.
• Slower acting (mins-hrs)

Non-steroid:

• Water soluble (derived from aa)
• bind to cell surface receptors -> activate signal transduction pathway.
• Activate existing enzymes.
• Faster acting (s-min)

Question 11

Describe the mechanism of cytoplasmic receptor activation.

Answer 11

• Ligand binds to receptor & dislodges repressor protein
• Ligand-receptor complex enters nucleus & binds to Hormone Response element in promoter region of DNA.
• Gene expression.

Question 12

Describe the mechanism of nuclear receptor activation.

Answer 12

• Lipid soluble hormones diffuse through plasma membrane
• bind to cytoplasmic (& migrate to nucleus) or nuclear receptors
• Hormone-receptor complex binds to hormone response element (Acts as TF).
• mRNA synthesis
• mRNA migrates & binds to ribosomes - protein synthesis.

Question 13

Compare ionotropic & metabotropic receptors.

Answer 13

Ionotropic: ionic ligand-receptor binding opens ion channels.
Metabotropic: ligand-receptor binding -> cascade of reactions via G protein linking.

Question 14

Briefly describe how a ligand-gated ion channel works.

Answer 14

First messenger binds to receptor -> conformational change -> molecule enters via ion channel.

Question 15

State the 4 GPCR families & their functions.

Answer 15

• Gα(s) stimulate AC&raquo_space; cAMP
• Gα(i) stimulate AC &laquo_space;cAMP
• Gα(q/11) stimulate PLC-β&raquo_space; IP3 & DAG
• Gα(12/13) activate Rho family of GTPases.

Question 16

What are enzyme-linked receptors responsible for?

Answer 16

Mediate actions of multiple growth factors, cytokines & hormones.
Regulate cell growth, proliferation & differentiation.

Question 17

For each receptor state ligand examples & their signal transduction pathway/target.

1. Ligand-gated ion channels
2. GPCRs
3. Enzyme linked receptors
4. Nuclear receptors

Answer 17

1. EC: GABA, (Cl-), ACh (Na+, K+, Ca++), ATP (Ca++, Na+, K+), glutamate (Na+, K+, Ca++).
   IC: sAMP (K+), IP3 (Ca++)
2. Neurotransmitters ACh & peptides (βy subunits activate ion channels)
   odorants, cytokines, lipids ( α subunit activates enzymes - cyclases, phospholipases)
3. ANP - receptor guanylyl cyclase
   TGF-β - ser/threo kinase
   insulin, EGF - tyrosine kinase
   IL-6, erythropoietin - tyrosine kinase-associated receptor
4. Steroid hormones: mineralocorticoids, glucocorticoids, androgens, estrogens, progestins.
   Miscellaneous hormones: thyroid, Vit D, retinoic acid, prostaglandins.
   Bind to regulatory sequences in DNA - alter gene expression.