Glycolysis: Allowed abbreviations

1. Glycolysis: Allowed abbreviations • Glucose • Glucose 6-phosphate • Fructose 6-phosphate • Fructose 1,6-bisphosphate • Dihydroxyacetone phosphate • Glyceraldehyde 3-phosphate • 1,3-Bisphosphoglycerate • 3-phosphoglycerate • 2-phosphoglycerate • Phosphoenolpyruvate • Pyruvate • N/A • G-6P • F-6P • F-1,6BP • DHAP • G-3P • 1,3-BPG • 3-PG • 2-PG • PEP • N/A

2. Fates of Other Sugars

5. GLUCONEOGENESIS

7. Gluconeogenesis Synthesis of "new glucose" from common metabolites • Humans consume 160 g of glucose per day • 75% of that is in the brain • Body fluids contain only 20 g of glucose • Glycogen stores yield 180-200 g of glucose • So the body must be able to make its own glucose

9. Substrates for Gluconeogenesis Pyruvate, lactate, glycerol, amino acids and all TCA intermediates can be utilized • Fatty acids cannot! • Why? • Most fatty acids yield only acetyl-CoA • Acetyl-CoA (through TCA cycle) cannot provide for net synthesis of sugars

10. Gluconeogenesis • Occurs mainly in liver and kidneys • Not the mere reversal of glycolysis for 2 reasons: • Energetics must change to make gluconeogenesis favorable (delta G of glycolysis = -74 kJ/mol • Reciprocal regulation must turn one on and the other off - this requires something new!

11. Gluconeogenesis Something Borrowed, Something New • Seven steps of glycolysis are retained: • Steps 2 and 4-9 • Three steps are replaced or bypassed: • Steps 1, 3, and 10 (the regulated steps!) • The new reactions provide for a spontaneous pathway (G negative in the direction of sugar synthesis), and they provide new mechanisms of regulation • Make sure you know the THREE BYPASS STEPS of Gluconeogenesis

13. 1st bypass reaction: Pyruvate → PEP Pyruvate is converted back to PEP in two steps. Not shown here is the transport process: since oxaloacetate is usually found in the mitochondrial matrix, it must be transported out into the cytosol. However, there is no transporter for oxaloacetate.

14. 1st bypass reaction: Pyruvate → PEP Therefore, oxaloacetate is reduced to malate first using malate dehydrogenase. Malate is transported out into the cytosol and then reoxidized back to oxaloacetate

15. 2nd bypass reaction: Fructose 1,6-Bisphosphate → Fructose 6-phosphate Technically the reverse of the glycolytic reaction, but it is mediated by a different enzyme.

16. 2nd bypass reaction: Glucose 6-Phosphate → Glucose • Mediated by a different enzyme.

17. Cori cycle

19. Pentose Phosphate Pathway