gluconeogenesis Flashcards
major substrates for gluconeogenesis during fasting
alanine- from pyruvate/branched chain aa in mm
glycerol- from FA
what is the most “direct” substrate for gluconeogenesis?
pyruvate
what 2 substances can be converted to pyruvate? enzymes?
- lactate with lactate dehydrogenase
- alanine with alanine aminotransferase
what is the cori cycle?
interactions that occurs between RBCs and skeletal mm during strenuous exercise in which lactate is exported to the liver and liver uses it to re-generate glucose via gluconeogenesis, net ATP = -4
what are the 4 enzymes in gluconeogenesis that replace the regulated steps in gluconeogenesis?
- pyruvate carboxylase
- PEP carboxykinase
- fructose-1,6-bisphosphatase
- glucose-6-phosphatase
what run in catalyzed by pyruvate carboxylase? inputs?
pyruvate is converted to oxaloacetate, cofactor is biotin and inputs are ATP and CO2
what reaction is catalyzed by PEP carboxykinase? inputs?
oxaloacetate is converted to PEP, inputs - GTP and CO2 is expelled
what is “released” by fructose-1,6-bisphosphatase and glucose-6-phosphatase?
Pi, ATP is not generated in gluconeogenesis
what is von Gierke’s disease?
glycogen storage dz characterized by deficiency of glucose-6-phosphatase
how is oxaloacetate exported from the mitochondria?
it is converted to malate by malate dehydrogenase in the mitochondria, then it travels to the cytosol where malate dehydrogenase converts it back.
how does glycerol contribute to gluconeogenesis?
glycerol kinase converts glycerol to glycerol-3-P; glycerol-3-P dehydrogenase then converts it to DHAP, DHAP enters gluconeogenesis
discuss use of alanine in gluconeogenesis
in muscle during a fast, branched chain aa are broken down to yield NH4+, NH4+ will combine with pyruvate to make alanine by alanine aminotransferase, alanine travels to the liver, where alanine aminotransferase removes NH4+ to make pyruvate that can enter gluconeogenesis and NH4+ enters urea cycle
what is the substrate for gluconeogenesis in the kidney?
glutamine
why is gluoneogenesis most important in the kidney?
renal medulla depends on glycolysis
how does glutamine enter gluconeogenesis?
glutamine is converted to glutamate by glutaminase; glutamate is converted to a-ketoglutarate by glutamate dehydrgoenase, a-ketoglutarate is then converted to oxaloacetate that enters gluconeogenesis
what is unique about gluconeogenesis that starts from glutamine?
yields ATP (because of it’s partial use of TCA cycle to generate oxaloacetate- NADH and FADH2 generated)
gluconeogenesis is inhibited by?
low energy states= want to break down glucose, not build it
3 energy inputs of gluconeogenesis
-ATP for pyruvate carboxylase
-GTP for PEP carboxykinase
- ATP for phosphoglycerate kinase
=3 x 2 pyruvate/glucose = 6 ATP
what is the source of ATP for gluconeogenesis in the liver?
from the partial oxidation of fatty acids to acetly-CoA
what is the role of PEPcarboxykinase in adipocytes?
not gluconeogenesis but for synthesis of glycerol-3-P
