Cell Surface Receptors
What are cell surface receptors?
Glycoproteins embedded in the cell membrane that bind to specific ligands
When is insulin secreted?
Fed state
What happens when GDP is exchanged for GTP on the alpha-subunit of the G-protein?
The alpha-subunit detaches and binds to adenylate cyclase to activate it.
What is the fate of glucose in glycolysis? What enzyme is increased in the fed state that is a part of glycolysis?
Glucose/G-6-P will be converted to pyruvate. The enzyme upregulated is glucokinase (GK).
What is glycogenolysis?
The breakdown of glycogen stores to yield glucose.
What is a 2nd messenger?
Molecules that relay the receptors signal and amplify it 1000's of times
What type of receptor is the insulin receptor? What does this mean? (hint autophosphorylation)
The insulin receptor is a tyrosine kinase receptor. This means that when insulin binds, the tyrosine residues are autophosphorylated. This triggers a signaling cascade.
What is the 2nd messenger of the glucagon signaling pathway?
cAMP
What is glycogen synthesis? What does glycogen synthase do?
Glycogen synthesis is the conversion of glucose to glycogen for storage. Glycogen synthase adds UDP-glucose to short chains of glycogen to lengthen them (storing more glucose).
In glycogenolysis, why does hepatic glycogen contribute to blood glucose levels but not myocytes?
Only the liver has glucose-6-phosphate, which converts glucose-6-phosphate to glucose.
What are the three domains of a cell surface receptor? What are their functions?
Extracellular ligand-binding domain - have residues exposed outside of cell to interact with and bind hormone
Transmembrane domain- anchors the receptor in the membrane
Cytoplasmic or Intracellular domain- interacts with molecules inside the cell, leading to generation of second messengers
What converts PIP2 to PIP3? What does PIP3 do?
PIP2 is converted (phosphorylated) by PI3K. PIP3 will phosphorylate AKt and activate it.
What occurs when cAMP is activated?
It amplifies the signal within the cell and activate protein kinases.
What is lipogenesis? What does pyruvate dehydrogenase do?
Lipogenesis is the conversion of glucose to fatty acids for storage. Pyruvate dehydrogenase converts pyruvate to acetyl-CoA.
What is gluconeogenesis? What genes are induced by glucagon in this pathway?
The conversion of non-carbohydrate precursors into glucose. Glucagon induces the trascription of PEPCK and glucose-6-phosphatase.
What are two cell surface receptors that we discussed today and what are their ligands?
Insulin receptor - insulin
G-protein coupled receptor - glucagon
How does the signaling cascade increase glucose uptake in myocytes?
Active AKt will cause GLUT4 to translocate to the cell surface of myocytes to increase glucose uptake.
What do protein kinases do?
Phosphorylate other enzymes, activating or inactivating them, depending on the enzyme.
Why/when is acetyl-CoA shuttled to de novo lipogenesis? What does acetyl-CoA carboxylase and FAS do in lipogenesis?
When the TCA cycle is running at full capacity, acetyl-CoA will be converted to fatty acids. Acetyl-CoA carboxlyase will convert acetyl-CoA to malonyl Co-A. FAS joins acetyl-CoA and malonyl-CoA to make longer fatty acid chains.
What is beta-oxidation? How do LCFA get into the mitochondrial matrix for beta-oxidation?
The cleavage of two-carbon fragments from FA's to yield acetyl-CoA. LCFA get into the mitochondrial matrix via CPT1 and CPTII (carnitine shuttle).
Can a cell surface receptor have more than one 2nd messenger? Can other cell surface receptors have the same 2nd messenger?
Yes! multiple hormones/receptors use the same 2nd messenger and one hormone/receptor can use multiple 2nd messengers.
How does the insulin signaling pathway increase glycogen synthesis?
What pathways does the glucagon signaling pathway induce?
Gluconeogenesis
Beta-oxidationGlycogenolysis
What enzymes are upregulated in the fed state?
GK- glycolysis
Glycogen synthase- glycogen synthesis
FAS- lipogenesisWhat type of acyl-CoA dehydrogenase is needed for the breakdown of FA's 10-12 carbons long in beta-oxidation?
MCAD (medium-chain Acyl-CoA dehydrogenase)