Chemistry 451
Lecture #25: Gluconeogenesis
Read: pg. 452-459 AND article on Rotenone from Fairbanks Daily News Miner
HW: pg. 465 (Study Exercises 7,8,9 AND Problems 6,7) AND pg. 491 (Problem 10)
Objectives:
- Compounds that can be converted to oxaloacetate can be converted to glucose via gluconeogenesis.
- Conversion of pyruvate to glucose via gluconeogenesis requires enzymes that bypass the three exergonic steps of glycolysis: Pyruvate carboxylase and PEP carboxykinase (PEPCK) bypass pyruvate kinase; fructose-1,6-bisphosphatase (FBPase) bypasses phophofructokinase (PFK); and glucose-6-phosphatase bypasses hexokinase.
- Gluconeogenesis is regulated by changes in enzyme synthesis and by allosteric effectors including fructose-2,6-bisphosphate (F2,6P) and acetyl CoA.
- Acetyl CoA allosterically activates pyruvate carboxylase.
- F2,6P is a regulatory molecule that potently allosterically inhibits FBPase and activates PFK. (In this case potently means that a
little F2,6P produces dramatic shifts in PFK and FBPase activity curves!)
Synthesis of F2,6P (from F6P) depends on the phosphorylation state of the bifunctional enzyme phospohfructokinase-2/fructose bisphosphatase-2 (PFK-2/FBPase-2)
Follow the above links to see scanned figures from Lehninger, Principles of Biochemistry (Shown in class).