Dec 23, 2015
Gluconeogenesis
By
Amr S. Moustafa, M.D.; Ph.D.
Assistant Prof. & Consultant, Medical Biochemistry Dept.
College of Medicine, [email protected]
Gluconeogenesis: An Overview
• Liver (mainly) and Kidneys
• Both mitochondria and Cytosol
• Exception: Glycerol, only cytosol
• Gluconeogenic substrates:
GlycerolLactateGlucogenic amino acidsPropionyl CoA
Gluconeqgenic Substrate: Glycerol
Glycerol Glycerol 3-phosphate*GK
Dihydroxyacetone phosphate
Glycerol 3-phosphate dehydrogenase
NAD+
NADH
Glucose
*GK: Glycerol kinase only in liver & kidneys
ATP ADP
Glucogenic Amino Acids
Glu, GlnPro, HisArg
MetValIle
PheTyr
Aminoacids
AspAsn
Gluconeogenic
Substrates
Glu, GlnPro, HisArg
MetValIle
PheTyr
Aminoacids
AspAsn
PyruvateGly, Ala, SerThr, Cys, TryAmino
acids
Propionyl CoA +
Lactate
Gluconeogenic Substrate: Lactate
(Cori Cycle)
Aerobic Glycolysis
Gluconeogenesis Pathway
Carboxylation of pyruvateTransport of OAA
Dephosphorylation of F 1,6-P
Dephosphorylation of G-6-P
Pruvate Carboxylase and PEP-CK
Fasting:Acetyl CoA(FAO)OAA(Gluconeogensis)
Pyruvate carboxylase + PEP-CK = Pyruvate kinase
Fructose 1,6-Bisphosphatase
Fructose 1,6-bisphosphatase = PFK-1
Glucose 6-Phosphatase
Glucose 6-phosphatase = GlucokinaseGlucose 6-phoshate translocase: G 6-P across ER membrane
(ER-Enzyme)
F – 2,6 – Bisphosphate and PFK-2: Fasting State
(high glucagon)
F – 2,6 – Bisphosphate and PFK-2: Well-fed State (high insulin)
Gluconeogensis:E-
Consumed
Six High-Energy Phosphate BondsFor Pyruvate toGlucose
2 ATP
2 ADP
Gluconeogenesis: Regulation
• Reciprocal control Gluconeogenesis & Glycolysis
• Allosteric: Acetyl CoA (Pyruvate carboxylase)
AMP or ATP F 2,6-Bisphosphate
• Glucagon ( I/G ratio)Allosteric ( F 2,6-Bisphosphate)
Covalent modification (Pyruvate kinase)
Induction (PEP-CK)
F 1,6-bisphosphatase