Chm 635-4

Chm 635-4 - 1 Allosterically inhibited by AMP and Fructose...

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Unformatted text preview: 1/19/2012 1 Allosterically inhibited by AMP and Fructose 2,6-bisphosphate. 1/19/2012 2 Glucose-6-Phosphatase converts glucose-6-P to Glucose in the Endoplasmic Reticulum • Presence of G-6-Pase in ER of liver and kidney cells makes gluconeogenesis possible • Muscle and brain do not do gluconeogenesis • G-6-P is hydrolyzed after uptake into the ER • The glucose-6-phosphatase system includes the phosphatase itself and three transport proteins, T1, T2 , and T3 . • T1 takes glucose-6-P into the ER, where it is hydrolyzed by the phosphatase • T2 and T3 export glucose and Pi, respectively, to the cytosol • Glucose is exported to the circulation by GLUT2 1/19/2012 3 Glucose-6-Phosphatase converts glucose-6-P to Glucose in the Endoplasmic Reticulum The Mechanism of Glucose-6-Phosphatase 1/19/2012 4 If Glycolysis & Gluconeogenesis are simultaneously active in a cell, it would constitute a " futile cycle " that would waste energy. Glycolysis: glucose + 2 NAD + + 2 ADP + 2 P i 2 pyruvate + 2 NADH + 2 ATP Gluconeogenesis: 2 pyruvate + 2 NADH + 4 ATP + 2 GTP glucose + 2 NAD + + 4 ADP + 2 GDP + 6 P i Glucagon Glucagon Glucagon 1/19/2012 5 PFK-2 and F-2,6-Bpase Are Two Activities of a Bifunctional, or Tandem, Enzyme 1/19/2012 6 PKA Hormonal regulation of [F2,6P]. (PFK2 and PK) 1/19/2012 7 Glucagon Glucagon Glucagon Fructose-1,6-bisphosphatase Hydrolysis of F-1,6-bisPase to F-6-P • Thermodynamically favorable – the G in liver is -8.6 kJ/mol • This is an allosterically regulated enzyme: – citrate stimulates – fructose-2,6-bisphosphate inhibits – AMP inhibits – The inhibition by AMP is enhanced by fructose-2,6-bisphosphate 1/19/2012 8 Fructose-1,6-bisphosphatase Fructose-1,6-bisphosphatase from pig with fructose-6- phosphate (orange), AMP (blue), and Mg 2+ (dark blue). Fructose-2,6-bisphosphate is a powerful inhibitor of fructose-1,6-bisphosphatase No AMP 1/19/2012 9 25 mM AMP Fructose-2,6-bisphosphate and AMP act synergistically to inhibit fructose-1,6-bisphosphatase Fructose-2,6-bisphosphate and AMP act synergistically to inhibit fructose-1,6-bisphosphatase Varying concentrations of AMP 1/19/2012 10 Cooperation between Glycolysis and Gluconeogenesis Glucose 6-Phosphate Has a Pivotal Metabolic Role in Liver 1/19/2012...
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Chm 635-4 - 1 Allosterically inhibited by AMP and Fructose...

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