Gluconeogenesis -
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Gluconeogenesis is the formation of glucose from non-carbohydrate precursors and occurs primarily in the liver and kidneys. Key substrates include lactate, glycerol, and glucogenic amino acids. The process is regulated by substrate availability and key enzymes such as pyruvate carboxylase and phosphoenolpyruvate carboxykinase. Gluconeogenesis is critical for maintaining blood glucose levels during periods of fasting or low carbohydrate intake.
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Gluconeogenesis -
- 2. The formation of glucose from non- carbohydrate precursors is called gluconeogenesis. Definition
- 3. Non-carbohydrate substance for gluconeogenesis are… Lactate Glycerol Glucogenic amino acids Propionic Acid Intermediates of the TCA.
- 4. Cytosol (although some precursors are produced in the mitochondria) Liver is the major tissue Kidney (during starvation) Location
- 5. Oxaloacetate Citrate α-Ketoglutarate Succinyl-CoA Fumarate MalateMalate Acetyl-CoA Pyruvate Pyruvate carboxylaseOxaloacetate phosphoenolpyruvate Pyruvate kinase GTP GDP + CO2 Phosphoenolpyruvate carboxykinase CO2, ATP, Biotin ADP+Pi Lactate Glucogenic AA Glucogenic AA Glucogenic AA Propionyl CoA Glucogenic AA Pyruvate Mitochondrial membrane
- 6. Glucose Glucose 6- phosphate Fructose 6-phosphate Fructose 1,6-bisphosphate 1,3-Bisphosphoglycerate 3-Phosphoglycerate 2-Phosphoglycerate Phosphoenol pyruvate Glyceraldehyde 3-p Dihydroxyacetone p ADP ATP Phosphofructokinase ADP ATP Glucokinase Hexokinase F 1,6 bisphosphatase Pi H2O Glucose 6 phosphatase Pi H2O Glycogen Glycerol Glycerol 3- P ADP NAD+ NADH + H G 3-P DH ATP
- 7. Substrate for gluconeogenesis Lactate Glycerol Glucogenic amino acids Propionic Acid Intermediates of the TCA.
- 8. Cori cycle or lactic acid cycle Glucose Pyruvate Lactate Lactate Pyruvate Glucose Gluconeogenesis Liver Muscles Glycolysis
- 9. Liver Muscles Glucose-Alanine Cycle Glucose Pyruvate Pyruvate NH4+ Alanine Transamination Glucose Alanine Transamination NH4+Urea Gluconeogenesis Alanine is the predominant amino acid released from muscle to liver during fasting.
- 10. Liver Muscles Cori cycle or lactic acid cycle and Glucose-Alanine Cycle Glucose Pyruvate Lactate Lactate Pyruvate NH4+ Alanine Transamination Glucose Alanine Transamination NH4+Urea Gluconeogenesis
- 11. Regulation of gluconeogenesis Since glycolysis & gluconeogenesis share the same pathway but in opposite direction, they may regulated reciprocally. The rate of gluconeogenesis depends on the Availability of substrate i.e substrate level regulation. Change in the activity of certain key enzymes, i.e. enzymatic regulation .
- 12. Gluconeogenesis is stimulated by the flow of its major substrate from peripheral tissues to liver. Lactate, produced by muscle during exrecise Glycerol released from adipose tissue Amino acids are released from muscle Thus, gluconeogenesis is stimulated during, Fasting Prolonged exercise By high protein diet, and Under stress conditions (due to increased epinephrine) Substrate Level Regulation
- 13. Gluconeogenesis is regulated by four key enzymes Pyruvate carboxylase Phosphoenolpyruvate carboxykinase Fructose-1,6 bisphoshatase Glucose -6 phosphatase. By the following mechanisms…… Induction or repression of enzymes. i.e change in the rate of synthesis of enzymes. The covalent modification by phosphorylation & dephosphorylation Allosteric activation or inhibition. Enzymatic Regulation
- 14. Significance of gluconeogenesis Gluconeogenesis meets the needs of the body for glucose & maintains glucose homeostasis; when carbohydrate is not available in sufficient amounts from the diet. Some tissues such as the brain, RBCs, lens, cornea & kidney medulla requires continuous supply of energy. Liver glycogen provides glucose supply for 12-18 hrs in absence of dietary intake of carbohydrate. As glycogen store start depleting, gluconeogenesis takes place, which ensure a continuous supply of glucose to the brain & other tissues It used to clear the products of the metabolism of other tissues from the blood, e.g., Lactate, produced by muscle & RBCs Glycerol produced by adipose tissues Propionyl-CoA produced by oxidation of odd chain fatty acids and carbon skeleton of some Aas.