General Features zTissues: yliver (80%) ykidneys (20%) zSubcellular location of enzymes ypyruvate carboxylase: mitochondrial yglucose-6-phosphatase: ER yall other enzymes cytoplasmic
Malate Shuttle zOAA produced in mitochondria zmitochondrial membrane impermeable to OAA zmalate transporter in mito. Membrane zmalate dehydrogenase in both mito and cyto zNADH produced in cyto also used in gluconeogenesis.
Precursers for gluconeogenesis figure 13-4 zAlanine and other amino acids ytransamination of pyruvate ypyruvate derived from glycolysis or from amino acid degradation yalanine cycle
Coordinated Regulation of Gluconeogenesis and Glycolysis zGluconeogenesis and Glycolysis are regulated by similar effector molecues but in the opposite direction yavoid futile cycles xPK vs PC&PEPCK xPFK-1 vs FDP’tase xGK vs G6P’tase
Coordinated Regulation of Gluconeogenesis and Glycolysis zRegulation of enzyme quantity zFasting: glucagon, cortisol yinduces gluconeogenic enzymes yrepresses glycolytic enzymes yliver making glucose zFeeding: insulin yinduces glycolytic enzymes yrepresses gluconeogenic enzymes yliver using glucose
Coordinated Regulation of Gluconeogenesis and Glycolysis zShort-term Hormonal Effects yGlucagon, Insulin xcAMP & F2,6P 2 zPFK-2 & FBPase-2 yA Bifunctional enzyme ycAMP xInactivates PFK-2 xActivates FBPase-2 xDecreases F2,6P 2 Reduces activation of PFK-1 Reduces inhibition of FBPase-1 zLow blood sugar results in yHi gluconeogenesis yLo glycolysis
Coordinated Regulation of Gluconeogenesis and Glycolysis zAllosteric Effects zPyruvate kinase vs Pyruvate carboxylase yPK - Inhibited by ATP and alanine yPC - Activated by acetyl CoA yFasting results in gluconeogenesis zPFK-1 vs FBPase-1 yFBPase-1 inhibited by AMP & F2,6P 2 yPFK-1 activated by AMP and & F2,6P 2 yFeeding results in glycolysis