gluconeogenesis Flashcards
Describe mechanism by which cortisol (glucocorticoid receptor included) causes synthesis of PEPCK in liver cell (to increase in the fasting state).
cortisol is a steroid hormone, intracellular receptor that resides in the cytosol. GR dimerize a specific gene transcription factor, binds to gene that codes for PEPCK at the glucocorticoid response element. gene that codes for PEPCK is expressed more because of cortisol in fasting state.
Name 3 inducible enzymes of gluconeogenesis
PEPCK, glucose 6 phosphatase, and fructose 1,6 bpase
how do glucagon signals cause a liver cell’s pyruvate kinase to be phosphorylated?
Glucagon binds to its receptor on the surface of liver cells. This receptor is a G protein-coupled receptor (GPCR), which is a type of transmembrane receptor that activates intracellular signaling pathways upon ligand binding.
Binding of glucagon to its receptor activates the G protein Gαs, which in turn activates adenylate cyclase, an enzyme that produces the second messenger cyclic adenosine monophosphate (cAMP).
cAMP activates protein kinase A (PKA), a serine/threonine kinase that phosphorylates target proteins.
PKA phosphorylates and activates cAMP response element-binding protein (CREB), a transcription factor that binds to DNA and regulates gene expression.
Activated CREB binds to the promoter region of the gene encoding pyruvate kinase, causing an increase in the transcription of the gene.
The newly synthesized pyruvate kinase protein is then phosphorylated by PKA at a specific serine residue (Ser^11 in the liver isoform), which reduces its activity.
Reduced pyruvate kinase activity leads to a decrease in the rate of glycolysis, which slows down glucose metabolism in the liver.
Regenerate response
What factors reciprocally control activities of phosphofructokinase 1 and furctose 1,6 bisphosphatase?
concentratoin of fructose 2,6 bisphosphate in the cytosol.
F2,6 BP is an allosteric activator of PFK-1 (fed state, glycolysis)
F2,6 BP is an allosteric inhibitor of F1,6 bpase (gluconeogensis)
PEPCK stands for…
phosphoenolpyruvate carboxykinase
how is the pyruvate kinase reaction inhibited?
this reaction is important for glycoloysis… so when we are fasting we don’t really want this happening. its inhibited by alanine, during the fed state there is lots of alanine arriving from muscle cells which turn off the pyruvate kinase. ATP is also an allosteric inhibitor, protein kinase A also inactivates it.
what is pyruvate carboxylase?
turns pyruvate into oxaloacetate.
how is pyruvate carboxylase activated?
allosterically activated by acetyl coA. during fasting state its coming from fatty acids as fuel (beta oxidation of fatty acids from adipocytes that are carried through blood via albumin).
what inhibits the pyruvate dehydrogenase reaction?
NADH and acetyl coA
What are the 3 most important noncarbohydrate precursors to liver’s synthesis of glucose?
pyruvate, lactate, and alanine.
What are the 3 most important noncarbohydrate precursors to liver’s synthesis of glucose?
glycerol, lactate, and alanine.
lactate into pyruvate
lactate dehydroenase, requires NAD+
alanine into pyruvate
alanine aminotransferase. alanine reacting with alpha ketoglutarate, requires PLP
glycerol to dihydroxyacetone phosphate?
2 steps… glycerol adding a phophate (using ATP) with glycerol kinase. glycerol 3 phosphate now becoming dihydroxyacetone phosphate via glycerol3-phosphate deydrogenase.
2 was for oxaloacetate to leave matrix of mitochondria
malate (using NADH which is plentiful from the fatty acids arriving) via malate dehydrogenase
aspartate (released in transamination reaction)
