Test 4 Flashcards
Not all signaling molecules act through PM receptors. Some bind to receptors found in the cytoplasm . Others bind to nuclear receptors. What type of signal could enter the cell by simple diffusion to activate a cytoplasmic receptor?
A) glucose
B) testosterone (steroid)
C) insulin (hydrophilic protein)
D) ATP
E) all of the above
B) testosterone (steroid)
A GPCR is a type of …. Membrane protein.
A) single-pass integral
B) monotopic integral
C) multi-subunit integral
D) peripheral
E) multi pass integral
E) multi pass integral
Define ‘signal transduction’.
Signal Transduction is the conversion of an extracellular message into (one of a range of) an intracellular response.
It involves a cascade of reactions that amplifies the original signal.
Means of a cell sensing a signal from its environment.
- Three steps:
(1) reception - cell senses a signal/environment using receptor proteins
(2) transduction: relaying the message
(3) response : activation of cellular response
Explain how a signal molecule which does not enter a cell can alter cell activities.
Ligand, or signal molecule, binds to receptor outside of the cell, which triggers a conformational change, resulting in a subsequent transduction/response scheme
Differentiate between an extracellular ligand and a cytoplasmic ligand.
Extracellular ligand: first messenger, binds to receptor outside cell
Cytoplasmic ligand: secondary messengers, propagate transduction
Describe the receptor-ligand interactions. Compare this interaction to previous intermolecular interactions discussed in class (e.g. enzyme-substrate, solute-transporter).
Receptor-ligand interaction is highly specific: fits into ligand-binding domain on receptor
- Interaction is temporary
- Receptors are saturable -> finite number of receptors
Differentiate between a paracrine hormone and an endocrine hormone.
Paracrine hormone/signaling: which local regulator diffuses through extracellular fluid
Endocrine hormone: synthesized in a particular location, secreted into the blood to travel long-distances, induces a response in a target cell/tissue located a distance from the original source
Explain signal amplification and its significance in cell signaling.
Relatively small quantities of ligand are often sufficient to elicit a response from target cell
At each step in the resulting cascade: a signaling intermediate stimulates the production of many molecules needed for the next step, and this is repeated over and over again
Producing more and more secondary messengers
- Ex. epinephrine: GPLR in 1:1 ratio, GPLR: G protein in 1:100 ratio, Glycogen phosphorylase: G-1-P in 10^6:10^8 ratio
Explain why not all cells respond to a given signaling molecule.
If a specific receptor is not expressed for that given signaling molecule, the corresponding cell will not respond
Describe in detail the class of proteins known as GPCRs (aka GPLRs).
- Multipass integral membrane proteins
- Ligand binding causes a change in receptor conformation that then activates a particular G protein
- Structure:
- 7 trans-membrane spanning domains
- N-terminal in EC, C-terminal in CYT
- ligand-binding domain (EC), G-protein interaction domain (CYT)
- Represent over half of the current drug targets
Describe in detail the class of proteins known as G proteins.
Family of guanine-nucleotide binding proteins
- G protein acts as an on/off switch: when bound to GDP, the G protein is inactive; GTP bound is active form
Two classes:
- heterotrimeric - peripheral membrane proteins, alpha beta and gamma subunits;
- monomeric (ex. Ras) - cytoplasmic, not linked to receptors
Illustrate the mechanisms involved in transducing a signal using G-proteins.
Heterotrimeric G proteins (Gαβγ) mediate signal transduction cascades via interactions with GPLRs
- Alpha subunit is largest: binds to GDP or GTP, has GTPase activity
- When Gα binds to GTP, it detaches from the Gβγ subunits which are permanently bound together
- Gα and/or Gβγ propagates signal cascade, depends on identity of G protein
- Mechanism:
1. ligand binds to receptor,
2. Gα releases GDP and binds to GTP activating G protein: subunits separate
3. G protein subunits activate or inhibit target proteins
4. Gα subunit hydrolyzes its bound GTP to GDP and becomes inactive
5. subunits recombine to form inactive G protein
Glycogenolysis involves …
A) glucose synthesis from non-carbohydrate sources
B) oxidation of glucose
C) hydrolysis of glycogen to release glucose-1-phosphate
D) phosphorolysis of glycogen to release glucose-1-phosphate
E) reduction of CO2 to form carbohydrates
D) phosphorolysis of glycogen to release glucose-1-phosp
The target of glycogen phosphorylase is glycogen. What reaction will glycogen phosphorylase catalyze involving glycogen?
A) it will remove phosphate from glycogen
B) it will transfer phosphate to glycogen, using ATP as a phosphate source
C) it will transfer phosphate to glycogen using P¡ as a phosphate source
D) it will hydrolyze glycogen
E) it will hydrogenate glycogen
C) it will transfer phosphate to glycogen using P¡ as a phosphate source
Glycogen phosphorylase will be activated by a …..and deactivated by a ……
A) kinase; phosphatase
B) phosphate; phosphorylase
C) phosphorylase; kinase
D) Phosphorylase; phosphatase
E) kinase ; phosphorylase
A) kinase; phosphatase
