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Gluconeogenesis
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Gluconeogenesis
Glucose
Glucogenic amino acids
Glycerols (from triglycerides)
Propionate(ruminants)
Krebs cycleintermediates
Lactate,pyruvate
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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…
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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
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Review of GlycolysisGlyceraldehyde-3-P
∆G+1 kJ/mol
1,3-bis PGA
3-PGA
2-PGA
PEP
Pyruvate
ADPATP
ADPATP –17 kJ/mol
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Bypasses of “Irreversible” Glycolysis Steps
ATP ADP
Glucose Glucose-6-P
Pi
Glucose-6-phosphatase
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Bypasses of “Irreversible” Glycolysis Steps
ATP ADP
Fructose-6-P Fructose-1,6-bisP
Pi
FBPase-1
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Bypasses of “Irreversible” Glycolysis Steps
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Cori Cycle: Lactate Salvage
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Glucose-Alanine Cycle
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Gluconeogenesis from Stored Fats In plants
Triacylglycerols
GlycerolFatty acids
β-oxidation
-Acetyl CoA Glyoxylate cycle
Oxaloacetate PEP carboxykinase
PEPGluconeogenesis
Glucose
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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
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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
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Fate of Pyruvate: Regulation
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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)
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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)
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Regulation by Fru-2,6-bisP
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Regulation by Fru-2,6-bisP
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Fru-2,6-bisP as Regulator
Fru-6-P
Fru-1,6-bisP
ATP
ADP
Pi
Glycolysis Gluconeogenesis
Fru-2,6-bisP
(in mammals)
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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]
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PFK-2 and FBPase-1: Same Protein!