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Glycolysis Rate Limiters

Glycolysis Rate Limiters. LDH Hexokinase PFK-1 NADH/NAD + ratio PHOS Ca 2+ Epinephrine. Lactate Dehydrogenase (LDH). Catalyzes the reaction of pyruvate to lactate Has a low K m resulting in a high affinity for pyruvate Has the highest V max of any glycolytic enzyme

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Glycolysis Rate Limiters

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  1. Glycolysis Rate Limiters LDH Hexokinase PFK-1 NADH/NAD+ ratio PHOS Ca2+ Epinephrine

  2. Lactate Dehydrogenase (LDH) • Catalyzes the reaction of pyruvate to lactate • Has a low Km resulting in a high affinity for pyruvate • Has the highest Vmax of any glycolytic enzyme • The system favors lactate production. • Any pyruvate not immediately entering the mitochondria is reduced to lactate.

  3. Hexokinase • Catalyze the reaction that turns glucose into Glucose 6-P • Regulated by its product Glucose 6-P • If G6-P increases too much, it binds to the hexokinase enzyme and slows the reaction rate. • Results in a sharp decrease in glucose uptake into the cell • This process is called Feedback or Product Inhibition

  4. Phosphofructokinase-1 (PFK-1) • Major regulatory enzyme for the glycolytic pathway flux from G6-P to pyruvate • Control is primarily based on changes in concentrations of several allosteric effectors

  5. Cytoplasmic NADH/NAD+ Ratio • Affects activity of Glyceraldehyde 3-phosphate Dehydrogenase • Catalyzes reaction: • NAD+ is oxidized to NADH and H+ • Generated NADH can be re-oxidized to NAD+ • Lack of NAD+ will halt glycolysis • Important for converting pyruvate into lactate • Increase in ratio, through reduction, slows glycolysis • Decrease in ratio, through oxidation, speeds glycolysis

  6. Glycogen Phosphorylase (PHOS) • Glycogen is the primary source of G6-P to fuel glycolysis • Breakdown of glycogen is dependent on the PHOS enzyme • Controlled through proportion of enzyme in the active GPa form vs. inactive GPb form

  7. Calcium Ion (Ca2+) • Regulates glycogen catabolism • Conversion of PHOS b (inactive) to PHOS a (active) depends on stimulation of glycogen phosphorylase kinase (GPK) by Ca2+ • Fast PHOS activation • Ca2+ released from sarcoplasmic reticulum immediately when muscles contract • 4 Ca2+ bind to calmodulin (subunit of GPK) to activate it • Active calmodulin can phosphorylate phosphorylase b to make it phosphorylase a

  8. Epinephrine • Released when you are aroused or anxious before competition • Mediates stimulation of glucose production by the liver in advance of muscular uptake • Slow PHOS activation • Epinephrine binds to its β adrenergic receptor on skeletal muscle • Starts cascade of activation events • Results in conversion of PHOS b to PHOS a

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