10/2 Gluconeogenesis Flashcards
effect of phosphorylation of glycogen synthase
deactivation (multiple pathways to do this)
effect of phosphorylation of glycogen phosphorylase
activation
precursors for gluconeogenesis
lactate, pyruvate, glycerol, amino acids, and any Krebs intermediate that can form oxaloacetate
source of glycerol for gluconeogenesis
from lipolysis of triglycerides in adipose tissue
hormonal effect of drop in blood [glucose]
(fasted state)
glucagon is dominant hormone
increases: glycogenolysis, gluconeogenesis, lipolysis (goal: make energy available)
decreases: liver glycolysis
hormonal effect of rise in blood [glucose]
(fed state)
insulin is dominant hormone
increases: glycogenesis, fatty acid synthesis, triglyceride systhesis, liver glycolysis (goal: store energy)
role of FA oxidation in gluconeogenesis
mitochondrial fatty acid oxidation produces the energy needed to drive gluconeogenesis (ATP, GTP, NADH)
lactate can also be the source of these through its conversion to pyruvate
how is glycogenolysis triggered in mm?
when ATP in skel mm is low, triggered
NO receptors for glucagon, so no diff btwn fed/fasted state
skel m lacks glucose 6-phosphatase (G6P–>glucose), so G6P is committed to glycolysis
m glycogen phosphorylase
chain degredation
Pi = activation
(+) AMP (but not in liver cells)
glucose does NOT inhibit it
m glycogen synthase
chain elongation
Pi = inactivation
(-) glycogen
source of lactate for gluconeogenesis
muscle and RBC glycolysis
source of amino acids for gluconeogenesis
alanine
from glycolysis and amino acid metabolism
source of pyruvate for gluconeogenesis
AAs, alanine, and lactate are converted into pyruvate, which is then converted into oxaloacetate
when does gluconeogenesis occur?
fasting, stress, high protein diet, prolonged exercise
two effects of Acetyl-CoA
activates pyruvate carboxylase
inhibits pyruvate dehydrogenase
what energy is required per one glucose molecule synthesized through gluconeogenesis
4 ATP, 2 GTP, 2 NADH
role of liver in maintaining blood [glucose]
in a fasted state, the liver’s gluconeogenesis is the only source of glucose. essential b/c the brain and RBCs require glucose but cannot synthesize their own. prevents hypoglycemia
four irreversible enzymes of glycolysis
glucokinase
phosphofructokinase-1
pyruvate kinase
pyruvate dehydrogenase
four enzymes of gluconeogenesis that circumvent (glycolysis’ irreversible enzymes)
pyruvate carboxykinase (pyruvate dehydrogenase)
phosphoenolpyruvate carboxykinase (pyruvate kinase)
fructose 1,6-bisphosphatase (phosphofructokinase-1)
glucose 6-phosphatase (glucokinase)
pyruvate carboxykinase (PC)
replaces pyruvate dehydrogenase
in mitochondria in fed and fasted state
pyruvate —> oxaloacetate
requires ATP and biotin
phosphoenolpyruvate carboxykinase (PEPCK)
replaces pyruvate kinase
in cytosol and mitochondria (isoforms)
oxaloacetate —> phosphoenolpyruvate
requires GTP
fructose 1,6-bisphosphatase (FBPase-1)
replaces phosphofructokinase-1
in cytosol
(+) low blood [glucose]
fructose 1,6-bisphosphate —> fructose 6-phosphate
glucose 6-phosphatase (G6Pase)
replaces glucokinase
in ER
glucose 6-phosphate –> glucose
T1: G6P into ER
T2: Pi into cytosol
T3: glucose into cytosol
