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Gluconeogenesis
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Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Jan 04, 2016

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Cecil Parsons
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Page 1: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Gluconeogenesis

Page 2: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Gluconeogenesis

Glucose

Glucogenic amino acids

Glycerols (from triglycerides)

Propionate(ruminants)

Krebs cycleintermediates

Lactate,pyruvate

Page 3: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates 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…

Page 4: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

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

Page 5: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Review of GlycolysisGlyceraldehyde-3-P

∆G+1 kJ/mol

1,3-bis PGA

3-PGA

2-PGA

PEP

Pyruvate

ADPATP

ADPATP –17 kJ/mol

Page 6: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Bypasses of “Irreversible” Glycolysis Steps

ATP ADP

Glucose Glucose-6-P

Pi

Glucose-6-phosphatase

Page 7: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Bypasses of “Irreversible” Glycolysis Steps

ATP ADP

Fructose-6-P Fructose-1,6-bisP

Pi

FBPase-1

Page 8: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Bypasses of “Irreversible” Glycolysis Steps

Page 9: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Cori Cycle: Lactate Salvage

Page 10: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Glucose-Alanine Cycle

Page 11: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Gluconeogenesis from Stored Fats In plants

Triacylglycerols

GlycerolFatty acids

β-oxidation

-Acetyl CoA Glyoxylate cycle

Oxaloacetate PEP carboxykinase

PEPGluconeogenesis

Glucose

Page 12: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

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

Page 13: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

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

Page 14: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Fate of Pyruvate: Regulation

Page 15: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

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)

Page 16: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

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)

Page 17: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Regulation by Fru-2,6-bisP

Page 18: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Regulation by Fru-2,6-bisP

Page 19: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

Fru-2,6-bisP as Regulator

Fru-6-P

Fru-1,6-bisP

ATP

ADP

Pi

Glycolysis Gluconeogenesis

Fru-2,6-bisP

(in mammals)

Page 20: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

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]

Page 21: Gluconeogenesis. Glucose Glucogenic amino acids Glycerols (from triglycerides) Propionate (ruminants) Krebs cycle intermediates Lactate, pyruvate.

PFK-2 and FBPase-1: Same Protein!