Gluconeogenesis
Gluconeogenesis
Glucose
Glucogenic amino acids
Glycerols (from triglycerides)
Propionate(ruminants)
Krebs cycleintermediates
Lactate,pyruvate
Roles of Gluconeogenesis Provides glucose for the brain Recycles lactate after exercise Lactose synthesis in ruminants Carbohydrate polymers in plants and bacteria
From CO2, acetate, fats, etc…
Review of GlycolysisGlucose
Glu-6-P
Fru-6-P
Fru-1,6-bisP
DHAP Glyceraldehyde-3-P
ATPADP
ATPADP
∆G–33 kJ/mol
–22 kJ/mol
Review of GlycolysisGlyceraldehyde-3-P
∆G+1 kJ/mol
1,3-bis PGA
3-PGA
2-PGA
PEP
Pyruvate
ADPATP
ADPATP –17 kJ/mol
Bypasses of “Irreversible” Glycolysis Steps
ATP ADP
Glucose Glucose-6-P
Pi
Glucose-6-phosphatase
Bypasses of “Irreversible” Glycolysis Steps
ATP ADP
Fructose-6-P Fructose-1,6-bisP
Pi
FBPase-1
Bypasses of “Irreversible” Glycolysis Steps
Cori Cycle: Lactate Salvage
Glucose-Alanine Cycle
Gluconeogenesis from Stored Fats In plants
Triacylglycerols
GlycerolFatty acids
β-oxidation
-Acetyl CoA Glyoxylate cycle
Oxaloacetate PEP carboxykinase
PEPGluconeogenesis
Glucose
Gluconeogenesis from Stored Fats In animals
Triacylglycerols
GlycerolFatty acids
Gluconeogenesis
Glucose
Glyceraldehye-3-P
Dihydroxyacetone-P
Glycerol-P
Glycerol kinase
Glycerol-P DH
Triose-P isomerase
CH2OH
CHOH
CH2OH
Gluconeogenesis from Propionate In ruminants
Cellulose, etc...
Propionate
Methylmalonyl-CoA
Succinyl-CoA
Oxaloacetate
PEP
Glucose
Protozoa, bacteria ferment
Propionyl-CoA carboxylase
B12
Krebs cycle
Galactose Lactose
Fate of Pyruvate: Regulation
Gluconeogenesis and Glycolysis Reciprocal regulation
Fru-6-P
Fru-1,6-bisP
ATP
ADP
Pi
PFK-1 FBPase-1
Net reaction: ATP ADP + P i
(a futile cycle)
Reciprocal Regulation of PFK-1 and FBPase-1
Both enzymes allosterically regulated by Fru-2,6-bisP
O
HO
OH
CH2
OH
CH2OOP P O
HO
OH
CH2
O
CH2OHOP
P
Fru-1,6-bisP(substrate/product)
Fru-2,6-bisP(allosteric regulator)
Regulation by Fru-2,6-bisP
Regulation by Fru-2,6-bisP
Fru-2,6-bisP as Regulator
Fru-6-P
Fru-1,6-bisP
ATP
ADP
Pi
Glycolysis Gluconeogenesis
Fru-2,6-bisP
(in mammals)
What Regulates [Fru-2,6-bisP]? Indirectly regulated by the hormone glucagon
Fru-6-P
Fru-2,6-bisP
ATP
ADP
Pi
PFK-2 FBPase-2
Glucagon:(in liver) }FBPase-2
PFK-2[Fru-2,6-bisP]
PFK-2 and FBPase-1: Same Protein!