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Glycolysis Rate Limiters  LDH  Hexokinase  PFK-1  NADH/NAD + ratio  PHOS  Ca 2+  Epinephrine.

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Presentation on theme: "Glycolysis Rate Limiters  LDH  Hexokinase  PFK-1  NADH/NAD + ratio  PHOS  Ca 2+  Epinephrine."— Presentation transcript:

1 Glycolysis Rate Limiters  LDH  Hexokinase  PFK-1  NADH/NAD + ratio  PHOS  Ca 2+  Epinephrine

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

3 Hexokinase Catalyze the reaction that turns glucose into Glucose 6-P Catalyze the reaction that turns glucose into Glucose 6-P Regulated by its product 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. 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 Results in a sharp decrease in glucose uptake into the cell This process is called Feedback or Product Inhibition 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 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 Control is primarily based on changes in concentrations of several allosteric effectors

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

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

7 Calcium Ion (Ca 2+ ) Regulates glycogen catabolism Regulates glycogen catabolism Conversion of PHOS b (inactive) to PHOS a (active) depends on stimulation of glycogen phosphorylase kinase (GPK) by Ca 2+ Conversion of PHOS b (inactive) to PHOS a (active) depends on stimulation of glycogen phosphorylase kinase (GPK) by Ca 2+ Fast PHOS activation Fast PHOS activation Ca 2+ released from sarcoplasmic reticulum immediately when muscles contract Ca 2+ released from sarcoplasmic reticulum immediately when muscles contract 4 Ca 2+ bind to calmodulin (subunit of GPK) to activate it 4 Ca 2+ bind to calmodulin (subunit of GPK) to activate it Active calmodulin can phosphorylate phosphorylase b to make it phosphorylase a Active calmodulin can phosphorylate phosphorylase b to make it phosphorylase a

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


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