Notes on Gluconeogenesis

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Overall Idea in Gluconeogenesis:

• This is the process by which non-carbohydrate precursors are converted to glucose.

• The brain and red blood cells are completely dependent upon glucose for energy needs.

• Occurs in the liver and, to a smaller extent, in the kidney cortex.

• Precursors that can be converted to glucose include lactate and pyruvate, citric acid cycle intermediates, and carbon skeletons of most amino acids.

• All these substances, however, are first converted to oxaloacetate - the starting point for gluconeogenesis.

• Only amino acids that can't be converted are leucine and lysine because their breakdown yields only acetyl-CoA.

• Fatty acids also can't be converted to glucose because fats are completely degraded to acetyl-CoA.

• Plants can convert acetyl-CoA to oxaloacetate through glyoxylate cycle.

Gluconeogenesis Reaction summary:

1. Pyruvate is converted to oxaloacetate; reaction catalyzed by pyruvate carboxylase.

2. Oxaloacetate is converted to phosphoenolpyruvate; reaction catalyzed by PEP carboxykinase (PEPCK).

3. Phosphoenolpyruvate converted to 2-phosphoglycerate by enolase.

4. 2-phosphoglycerate converted to 3-phosphoglycerate by phosphoglycerate mutase.

5. 3-phosphoglycerate converted to 1,3-bisphosphyglycerate by phosphoglycerate kinase.

6. 1,3-bisphosphyglycerate converted to glyceraldehyde-3-phosphate by glyceraldehyde-3-phosphate dehydrogenase.

7. glyceraldehyde-3-phosphate interconverts to dihydroxyacetone phosphate in a reversible reaction by triose phosphate isomerase.

8. Glyceraldehyde-3-phosphate converted to fructose-1,6-bisphosphate by aldolase.

9. Fructose-1,6-bisphosphate is converted to glucose-6-phosphate by phosphofructokinase.

10. Glucose-6-phosphate is converted to glucose by hexokinase.

Gluconeogenesis Regulation:

• Phosphofructokinase is inhibited by ATP/citrate and activated by AMP/F2,6P.

• Fructose bisphosphatase is inhibited by AMP/F2,6P.

• Pyruvate kinase inhibited by alanine and activated by F1,6P and acetyl-CoA.

• PFK-2 inhibited by citrate and activated by AMP/F6P/Pi.

• FBPase-2 inhibited by F6P and activated by glycerol-3-P.

• PEPCK is controlled by transcriptional regulation of the gene encoding for it. The gene is stimulated by glucagon, thyroid hormone and glucocorticoids, and inhibited by insulin.

Additional Readings:

Basic Biochemistry

1. Nucleic Acid Structure and Organization
2. DNA Replication and Repair
3. Transcription and RNA Processing
4. Genetic Code, Mutations, and Translation
5. Genetic Regulation
6. Recombinant DNA
7. Amino Acids, Proteins, Enzymes
8. Hormones
9. Vitamins
10. Energy Metabolism
11. Glycolysis and Pyruvate Dehydrogenase
12. Citric Acid Cycle and Oxidative Phosphorylation
13. Glycogen, Gluconeogenesis, and Hexose Monophosphate Shunt
14. Lipid Synthesis and Storage
15. Lipid Mobilization and Catabolism
16. Amino Acid Metabolism Disorders
17. Purine and Pyrimidine Metabolism
18. Electron Transport
19. Citric Acid Cycle and Glyoxylate Cycle
20. Glycolysis
21. Pyruvate Metabolism
22. Mitochondrial ATP formation
23. Gluconeogenesis
24. Glycogen Metabolism
25. Nitrogen Fixation (Metabolism) reactions, and Heme Metabolism
26. Amino Acid Metabolism
27. What is Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)?

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