Regulation of Glycolysis and gluconeogenesis (lecture 31)

arne1's version from 2015-09-19 15:16


Question Answer
Regulated enzymes of glycolysis (catalyze 3 irreversible steps)Hexokinase, Glucokinase (hepaticytes and pancreatic beta-cells), PFK-1, Pyruvate kinase
Glucokinase is found in hepatocytes
MODY 2Genetic deficiency of glucokinase can lead to maturity onset diabetes of the young Type 2. impaired insulin secretion from beta cells. chronic mild hyperglycemia.
Vmax of glucokinaselarge. Can phosphorylate a large amount of glucose. Has a large Km and thus low affinity for glucose.
glycolysis allowssubstrate level phosphorylation of ADP in cytosol. essential in RBCs (no mitos)
when does FA synthesis in hepatocytes take place>high insulin/glucagon ratio
high levels of AMP overcomePFK-1 inhibition by ATP (in liver hig AMP may indicate damage)
PFK-1 is allosterically activated byAMP (glycolysis is activated), and Fru 2,6-bisP (formed by bifunctional enzyme)
skeletal musclePFK-2 activity forms F 2,6-bP for glycolysis during muscle contraction
Enzymes of gluconeogenesis that are regulatedglucose-6-phosphatase. Fru-1,6-bisphosphatase, PEP carboxykinase, Pyruvate carboxylase (all catalyze irreversible steps)
substrates for gluconeogenesislactate, AA's(ala and gln), and glycerol. NAD+, PLP and biotin needed as coenzymes
pyruvate carboxylaserequires biotin has a coenzyme. carboxylates pyruvate to oxaloacetate
Insulin (high blood glucose) effectleads to dephosphorylated bifunctional enzyme. PFK-2 is active and forms fructose 2,6-bisP. glycolysis is more active.(Bpase-2 inhibited)
Glucagon (low blood glucose) effectphosphorylated bifunctional enzyme. BPase-2 is active and degrades fructose 2,6 bisP. Gluconeogenesis is more active. (PFK-2 inhibited)
ATP inhibitsPFK-1 and pyruvate kinase --> glycolysis stopped
Acetyl CoA activates --> pyruvate carboxylase --> gluconeogenesis occurs
Question Answer
glucose 6-P inhibitshexokinase -->glycolysis, no gluconeogenesis
fructose 6-P inhibitsglucokinase -->glycolysis, no gluconeogenesis
AMP and fructose 2,6 bisphosphate activatesPFK-1, inhibits fructose 1,6 bisphosphatase
Fructose 1,6 bisP activateshepatic PK --> no gluconeogenesis
Alanine inhibitshepatic PK --> no gluconeogenesis