Uploaded byDhiraj Trivedi
Class 4 gluconeogenesis
Gluconeogenesis is the synthesis of glucose from non-carbohydrate sources, primarily occurring in the liver and, to a lesser extent, in the kidney and intestine. This process is essential for maintaining blood glucose levels, especially during fasting, and involves key enzymes and pathways that convert substrates such as lactate, glycerol, and amino acids into glucose. Disruptions in gluconeogenesis can lead to serious health issues, including hypoglycemia and acidosis.
In this document
Powered by AI
Introduction to gluconeogenesis, synthesis of glucose from non-carbohydrate sources, importance for tissues like the brain and erythrocytes.
Failure leads to hypoglycemia causing brain dysfunction, coma, and potential death; excessive gluconeogenesis may cause hyperglycemia.
Primary sites are liver (85%) and kidney/intestine (15%); during fasting, kidneys may contribute up to 40%.
Pathways involved include TCA cycle and glycolysis reversal; consuming six ATP per glucose synthesized.
Key enzymes: Pyruvate carboxylase, PEP carboxykinase, Fructose-1,6-bisphosphatase, and Glucose-6-phosphatase.
Lactate from muscles converted to glucose in liver via the Cori cycle; involves pyruvate conversion.
List of reversible glycolysis steps involved in gluconeogenesis.
Two key bypass reactions facilitated by specific enzymes; regulation is tissue-specific.
Regulated by key enzymes; Activators include glucagon and acetyl-CoA; Inhibitors include insulin and AMP.
Maintains blood glucose levels, removes lactate, supplies glucose to muscles, and regulates acid-base balance.
Energy cost: six ATP and GTPs required for synthesizing one glucose; also involves NADH.
Pathways converting glycerol to glucose for use by extrahepatic tissues.
Cori cycle's function in lactate removal and glucose replenishment in active skeletal muscle.
Importance of amino acids, particularly in starvation, and their entry points into gluconeogenic pathways.
More Related Content
Similar to Class 4 gluconeogenesis
Class 4 gluconeogenesis
- 1.
- 2. Gluconeogenesis • Synthesis ofnew glucose • Also called as endogenous glucose production • Required because – • Erythrocyte, lens, testes and renal medulla exclusively use glucose for ATP. • Brain requires glucose but in starvation can adapt to use ketone bodies • To clear lactic acid from skeletal muscle and erythrocyte • To some extent reduce NH3 toxicity
- 3. Gluconeogenesis • Failure ofgluconeogenesis • leads to Hypoglycemia causes brain dysfunction • leads to coma and may be death. • Ketoacidosis, Lactic acidosis • Excessive gluconeogenesis leads to hyperglycemia
- 4. 85% 15% Gluconeogenesis • Majorsite of Gluconeogenesis • Liver – contribute 85%, • Kidney -- kidney and intestine contributes 15% • But - During prolonged fasting kidney can contribute up to 40% • Gluconeogenic substances • Pyruvate, Lactate, Glycerol, Propionic acid • Glycogenic amino acids --Alanine, glutamine,
- 5. Gluconeogenesis • Pathways involvedin gluconeogenesis are • TCA cycle • glycolysis --- Reversal of seven reactions • Some special reactions like • Cori cycle and Glucose alanine cycle • Adipose tissue -- Glycerol • Consumes six moles of ATP per glucose synthesized
- 6. Key reactions ofgluconeogenesis Involves Conversion of 1. pyruvate to phosphoenolpyruvate 2. Fructose 1,6 Bisphosphate to Fructose 6 Phosphate 3. Glucose 6 Phosphate to Glucose
- 7. Key Enzymes ofgluconeogenesis Pyruvate Phosphoenol Pyruvate 1. Pyruvate carboxylase 2. PEP carboxy kinase Fructose 1,6 Bisphosphate Fructose 6 Phosphate 3. Fructose 1,6 Bis Phosphatase Glucose Glucose 6 Phosphate 4. Glucose 6 Phosphatase
- 8. Gluconeogenesis from Lactate Lactateproduced in skeletal muscle , RBC brought to liver by Cori cycle Pyruvate Lactate NADH + H + NAD+ Lactate DH In cytosol Pyruvate Enters mitochondria
- 9. Cytoplasm Mitochondria Oxaloacetate Pyruvate Pyruvate Lactate NADH + H+ NAD+LDH Malate ADP + Pi CO2 + ATP Pyruvate carboxylase (Biotin) NADH + H + NAD+ MDH 1 Malate Oxaloacetate PEP X NADPH + H + NADP+ MDH 2 PEP CK First bypass reaction in gluconeogenesis Malate shunt GTP GDP + CO2
- 10.
- 11. Reversible steps of glycolysis Phosphoenolpyruvate 2- Phosphoglycerate 3- Phosphoglycerate 1,3- Bis Phosphoglycerate Glyceraldehyde 3- phosphate Fructose 1-6 Bisphosphate Reactions taking place in cytosol
- 12. Bypass 2 Fructose-1,6-bisphosphate toFructose-6-phosphate Enzyme is present in Liver, kidney and skeletal muscle Absent in heart and smooth muscle Fructose 1, 6 BisPhosphate Fructose 6 Phosphate Fructose 1,6 bisPhosphatease H2O Pi Inhibitores -- AMP, F2,6 BP , Insulin Activators -- ATP, Citrate, Glucagon X
- 13. Bypass 3 Glucose-6-phosphate toGlucose • Glucose 6 Phosphatase is found only in liver and kidney • Absent in muscle & adipose tissue , brain • (Reaction takes place in smooth endoplasmic reticulum) Glucose 6 Phosphate Free Glucose Glucose 6 Phosphatase H2O Pi Glucagon Insulin X
- 15. Regulation of Gluconeogenesis controlledby Regulating key enzymes of irreversible steps Activators / inducers Inhibitors / repressors Glucagon Acetyl CoA Citrate, ATP Glycogenic amino acids Carbohydrate feeding Insulin AMP Fasting state / hypoglycemia Diabetes
- 16. Significance of Gluconeogenesis •Keep blood glucose level stable • Remove lactate form skeletal muscle, RBC • Supply glucose to active skeletal muscle • Replenish liver Glycogen • Utilizes glycerol and propionate from adipose tissue • Regulate acid base balance
- 17. Energetics of Gluconeogenesis •Two high energy phosphate bonds one from ATP and one from GTP are hydrolyzed during conversion of pyruvate to PEP • As 2 Pyruvate required for one glucose 2 ATP and 2 GTP are used • Two more ATP required for conversion of 3-PG to 1,3-BPG • Therefore total Six ATP required for one glucose synthesis • Also NADH is used up and hence additional 6 ATP lose
- 18.
- 19. Triacyl glycerol glycerol Free fatty Acid glycerol glycerol Glycerol3 phosphate DHAP Glyceraldehyde 3 P Glucose Glucose For Extra hepatic Tissue Glycerokinase G3PDH
- 21. Cori cycle removal ofLactate and replenishing of glucose to skeletal muscle Pathway operate in active skeletal muscle Gluconeogenesis in liver from lactate
- 22.
- 23. Why skeletal musclerequire Cori cycle? In active skeletal muscle mitochondria is less NADH / NAD ratio is low as compared to liver and heart muscle Hence to continue glycolysis and generate ATP Reduction of pyruvate is required this generates Lactate If Lactate accumulate it causes Lactic acidosis Hence it should be removed through Cori cycle.
- 24. Glucose alanine cycle Importantin starvation Gluconeogenesis form Glycogenic amino acids
- 25.
- 26.
- 27. CitrateMalate Fumarate Succinyl CoA α-Ketoglutarate Oxaloacetate oxalosuccinate Aspartate Glutamic acid Histidine Proline Hydroxyproline Arginine Ornithine Valine Isoleucine Methionine Phenylalanine Tyrosine Glycine Serine Alanine Cysteine Threonine Pyruvate Entry of amino acids in TCA cycle
- 28.