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29 Cards in this Set
- Front
- Back
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What is the Melanocortin Receptor? |
The melanocortin receptor is a transmembrane G protein-coupled receptor of the rhodopsin family. |
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What do loss of function mutations in the melanocortin receptor result in? |
Defects in the melanocortin receptor predispose to obesity due to its role in binding appetite supressing hormones. |
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Describe the structure of Protein Kinase A. |
Protein Kinase A (PKA) is a tetramer of 2 regulatory and 2 catalytic sub units. |
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How does cAMP interact with protein kinase A (PKA) ? |
cAMP is an allosteric ligand activator of PKA. It binds to grooves in the regulatory sites changing the conformation of PKA thus releasing the catalytic sites from the structure. |
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What is Allosteric Regulation? |
The regulation of a protein by binding an effector molecule at a site other than the enzymes active site. |
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Why is adrenaline leading to glucose release a good example of an amplification cascade? |
Adrenaline released: 10 -9 M Glucose released: 10 -6M The release of the glucose far outweighs the overall release of the adrenaline. |
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What is gustducin? |
Gustducin is a Heterotrimeric G protein found in the tasting system which allows the tasting of sweet molecules. |
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How does gustducin cause an effect? |
1. Sweet tasting molecule binds to sweet taste receptor which is bound to the Ggust (Gustducin) protein. 2. The Ggust protein becomes activated, allowing binding of GTP to the alpha subunit. 3. The gustducin alpha subunit activates adenylyl cyclase 4. Adenylyl cyclase converts ATP to cAMP 5. cAMP activates Protein Kinase A 6. Activated PKA phosphorylates a potassium channel 7. Potassium channel closes as a result. |
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What are the main 2 types of alpha subunit on g proteins? |
GaI - inhibitory GaS - Stimulatory |
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How can we investigate which type of G alpha subunit is part of a G protein? |
We can use inhibitors. |
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What is the effect of the Gholera toxin? |
The gholera toxin locks GaS subunits in an activated state. This leads to repeated stimulation of adenylyl cyclase and thus a massive increase in cAMP in cells where GaS and Gholera toxin are both present. |
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How is 'Whooping Cough' related to investigation of G alpha subunit function? |
Whooping cough is caused by Bordetella pertussis. Which produces a GaI subunit inhibitor - Pertussis toxin. This results in the hyperaccumulation of cAMP in cells where the GaI subunit cannot inactivate adenylyl cyclase. We can isolate pertussis toxin from Bordetella pertussis and use it independently to identify GaI subunits. |
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How does pertussis toxin inhibit the action of GaI subunits? |
ADP ribosylation of GaI locks GaI in a GDP bound state preventing its activation. |
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How is cAMP degraded? |
Phosphodiesterase and water convert it into 5' AMP by breaking the Oxygen bonds to the cyclic ring. |
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Including detail on intracellular signalling processes; How does low blood glucose result in a decrease of glycogen synthesis? |
Low blood glucose --> Releases glucagon from pancreas alpha cells --> increase in cAMP --> activates protein kinase A --> deactivates glycogen synthase --> decreased glycogen synthesis! |
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Including detail on intracellular signalling processes; How does low blood glucose result in an increase of glycogen synthesis? |
High blood glucose --> release of insulin from pancreas beta cells --> increase in protein Kinase B activity --> Decrease in Glycogen synthase kinase 3 Activity (GSK-3) --> activation of glycogen synthase --> increased glycogen synthesis. |
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What is the role of Glycogen synthase kinase 3 (GSK-3) in regulating blood glucose? |
GSK-3 is a protein kinase which phosphorylates serine or threonine residues on its target substrate. In blood glucose regulation GSK-3 phosphorylates three C-Terminal serine residues, thus reducing its activity. |
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How is the insulin receptor formed? (genes, subunits, bonds etc.) |
Both the alpha and beta subunits are encoded from the same gene - thus they are derived from the same peptide by proteolytic cleavage. Yielding 2 subunits which are later linked via disulfide bridges to form the final insulin receptor. |
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What are the steps of the insulin receptor pathway? |
1. Insulin receptor is activated by the binding of insulin. 2. Insulin receptor phosphorylates the protein 'IRS-1' 3. Phosphorylated IRS-1 activates the PI-3K membrane bound enzyme 4. P1-3K phosphorylates PIP2 --> PIP3 5. PIP3 binds to PDK-1 activating it 6. PDK-1 activates Protein Kinase B 7. Protein Kinase B inactivates GSK-3 through phosphorylation 8. Glycogen synthase no longer phosphorylated into an inactive form and becomes active. |
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How is glycogen synthase maintained in an inactive state in the insulin synth pathway? |
Maintained in this state by a protein phosphatase |
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How do protein kinases phosphorylate their targets? |
Protein Kinases phosphorylate their targets by transferring the gamma phosphate of ATP to particular AA residues. |
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What do protein phosphatases do? |
Remove phosphates from their substrates. |
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What is the overall effect of insulin on muscle? |
Activates enzymes of hexose metabolism leading to storage of glycogen. |
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What are the specific effects of insulin on myocytes? |
1. Opens GLUT4 channels - allowing uptake of glucose. 2. Activates Hexokinase which converts glucose to G-6-Phosphate 3. Activates glycogen synthase which converts UDP glucose to glycogen. |
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Describe the structural properties of glycogen. |
Branched storage polysaccharide of animal cells. Each chain has 12-14 glucose residues alpha 1 --> 6 branch point. |
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How is glycogen synthesis initiated? |
Initiated by phosphorylation of a peptide. |
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What is the donor of glucose in glycogen synthesis? |
UDP glucose - the UDP is released |
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How is the glycogen chain extended? |
By successive transfers of glucose by glycogen synthase. |
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What is UDP? |
A sugar nucleotide made up of UTP and a glucose - 1 - phosphate |
