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Gluconeogenesis. Definition : Non Carbohydrate Glucose Site : Liver (80%), Kidney 20%) ? Small Intestine Why Glucose is very important! Brain always requires glucose In muscle as substrate for ATP production without oxygen Erythrocyte use only glucose for energy production
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Gluconeogenesis • Definition : Non Carbohydrate Glucose • Site : Liver (80%), Kidney 20%) ? Small Intestine Why Glucose is very important! • Brain always requires glucose • In muscle as substrate for ATP production without oxygen • Erythrocyte use only glucose for energy production • Mammary gland lactose Gluconeogenesis : For lactate clearance In Ruminant propionic acid is substrate for gluconeogenesis
Lactic Acid Glucose The path : TCA Cycle and reversal of glycolysis with four additional enzymes: • Pyruvate Carboxylase • PEP Carboxykinase • F 1,6 BPase • G 6Pase Glycerol Glucose Glycerol from lipolysis ( break down of Triglyceride) taken up by the liver Glycogenic amino acids glucose
ATP HCO3- Mg++ ADP + Pi
PEP Carboxykinase • Human, cow and guinea pig, in the mitochondria and in the cytoplasm • In rats only in the mitochondrions • In birds and marmots only in the mitochondrion Malate andPEP in human exit from the mitochondrion In rats malate transported out of the mitochondrion and converted to oxaloacetate
Fructose-6-phosphate 6-phosphofructo -1-kinase Fructose 1,6-bisphosphatase Fructose 1,6-bisphosphate Gluconeogenesis and Glycolysis are reciprocally regulated • Fructose 1,6-bisphosphatase is main regulatory step in gluconeogenesis. • Corresponding step in glycolysis is 6-phosphofructo-1-kinase (PFK-1). • These two enzymes are regulated in a reciprocal manner by several metabolites. + Citrate - AMP - F 2,6-BP Citrate - AMP + F 2,6-BP + Reciprocal control—prevents simultaneous reactions in same cell.
Ala Cys Gly Ser Thr Trp Fates of Amino Acid degradation products Glucose Leu Lys Phe Trp Tyr Pyruvate Ile Phosphoenol- pyruvate Acetyl CoA Acetoacetate Citrate Asn Asp Oxaloacetate Isocitrate Gln Citric Acid Cycle Malate Arg His Pro Phe a-Ketoglutarate Glu Tyr Fumarate Ile Met Thr Val Succinyl CoA Glucogenic Ketogenic Both Glucogenic & Ketogenic Succinate
Ala Cys Gly Ser Thr Trp Fates of Amino Acid degradation products Glucose Leu Lys Phe Trp Tyr Pyruvate Ile Phosphoenol- pyruvate Acetyl CoA Acetoacetate Citrate Asn Asp Oxaloacetate Isocitrate Gln Citric Acid Cycle Malate Arg His Pro Phe a-Ketoglutarate Glu Tyr Fumarate Ile Met Thr Val Succinyl CoA Glucogenic Ketogenic Both Glucogenic & Ketogenic Succinate