Gluconeogenesis By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU

Gluconeogenesis: An Overview Liver (mainly) and Kidneys Both mitochondria and Cytosol Exception: Glycerol, only cytosol Gluconeogenic substrates: Glycerol Lactate Glucogenic amino acids Propionyl CoA

Gluconeqgenic Substrate: Glycerol GlycerolGlycerol 3-phosphate *GK Dihydroxyacetone phosphate Glycerol 3-phosphate dehydrogenase NAD+ NADH Glucose *GK: Glycerol kinase only in liver & kidneys ATPADP

Glucogenic Amino Acids Glu, Gln Pro, His Arg Met Val Ile Phe Tyr Amino acids Asp Asn

Gluconeogenic Substrates Glu, Gln Pro, His Arg Met Val Ile Phe Tyr Amino acids Asp Asn Pyruvate Gly, Ala, Ser Thr, Cys, Try Amino acids Propionyl CoA + Lactate

Gluconeogenic Substrate: Lactate (Cori Cycle)

Aerobic Glycolysis

Gluconeogenesis Pathway Carboxylation of pyruvate Transport 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 = Glucokinase Glucose 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 Bonds For Pyruvate to Glucose 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