Gluconeogenesis By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry...
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Transcript of Gluconeogenesis By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry...
![Page 1: Gluconeogenesis By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com.](https://reader036.fdocuments.us/reader036/viewer/2022062407/56649da25503460f94a8e98a/html5/thumbnails/1.jpg)
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Gluconeogenesis
By
Amr S. Moustafa, M.D.; Ph.D.
Assistant Prof. & Consultant, Medical Biochemistry Dept.
College of Medicine, [email protected]
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Gluconeogenesis: An Overview
• Liver (mainly) and Kidneys
• Both mitochondria and Cytosol
• Exception: Glycerol, only cytosol
• Gluconeogenic substrates:
GlycerolLactateGlucogenic amino acidsPropionyl CoA
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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
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Glucogenic Amino Acids
Glu, GlnPro, HisArg
MetValIle
PheTyr
Aminoacids
AspAsn
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Gluconeogenic
Substrates
Glu, GlnPro, HisArg
MetValIle
PheTyr
Aminoacids
AspAsn
PyruvateGly, Ala, SerThr, Cys, TryAmino
acids
Propionyl CoA +
Lactate
![Page 7: Gluconeogenesis By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com.](https://reader036.fdocuments.us/reader036/viewer/2022062407/56649da25503460f94a8e98a/html5/thumbnails/7.jpg)
Gluconeogenic Substrate: Lactate
(Cori Cycle)
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Aerobic Glycolysis
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Gluconeogenesis Pathway
Carboxylation of pyruvateTransport of OAA
Dephosphorylation of F 1,6-P
Dephosphorylation of G-6-P
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Pruvate Carboxylase and PEP-CK
Fasting:Acetyl CoA(FAO)OAA(Gluconeogensis)
Pyruvate carboxylase + PEP-CK = Pyruvate kinase
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Fructose 1,6-Bisphosphatase
Fructose 1,6-bisphosphatase = PFK-1
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Glucose 6-Phosphatase
Glucose 6-phosphatase = GlucokinaseGlucose 6-phoshate translocase: G 6-P across ER membrane
(ER-Enzyme)
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F – 2,6 – Bisphosphate and PFK-2: Fasting State
(high glucagon)
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F – 2,6 – Bisphosphate and PFK-2: Well-fed State (high insulin)
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Gluconeogensis:E-
Consumed
Six High-Energy Phosphate BondsFor Pyruvate toGlucose
2 ATP
2 ADP
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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