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!