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

Fates of Other Sugars

GLUCONEOGENESIS

Synthesis of "new glucose" from common metabolites 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 3

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 4

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! 5

Something Borrowed, Something New 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 6

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.

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

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.

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

Cori cycle

Pentose Phosphate Pathway