glycolysis rate limiters
DESCRIPTION
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 - PowerPoint PPT PresentationTRANSCRIPT
GlycolysisGlycolysis Rate Rate LimitersLimiters
LDHLDHHexokinaseHexokinase
PFK-1PFK-1NADH/NADNADH/NAD++ ratio ratio
PHOSPHOSCaCa2+2+
EpinephrineEpinephrine
Lactate Dehydrogenase (LDH)Lactate Dehydrogenase (LDH)
Catalyzes the reaction of pyruvate to lactateCatalyzes the reaction of pyruvate to lactate
Has a low KHas a low Kmm resulting in a high affinity for pyruvate resulting in a high affinity for pyruvate
Has the highest VHas the highest Vmaxmax of any glycolytic enzyme of any glycolytic enzyme The system favors lactate production. The system favors lactate production. Any pyruvate not immediately entering the mitochondria is Any pyruvate not immediately entering the mitochondria is
reduced to lactate.reduced to lactate.
HexokinaseHexokinase
Catalyze the reaction that turns glucose into Catalyze the reaction that turns glucose into Glucose 6-PGlucose 6-P
Regulated by its product Glucose 6-PRegulated by its product Glucose 6-P If G6-P increases too much, it binds to the If G6-P increases too much, it binds to the
hexokinase enzyme and slows the reaction rate.hexokinase enzyme and slows the reaction rate. Results in a sharp decrease in glucose uptake into Results in a sharp decrease in glucose uptake into
the cellthe cell This process is called Feedback or Product This process is called Feedback or Product
InhibitionInhibition
Phosphofructokinase-1 (PFK-1)Phosphofructokinase-1 (PFK-1)
Major regulatory enzyme for the glycolytic Major regulatory enzyme for the glycolytic pathway flux from G6-P to pyruvatepathway flux from G6-P to pyruvate
Control is primarily based on changes in Control is primarily based on changes in concentrations of several allosteric effectorsconcentrations of several allosteric effectors
Cytoplasmic NADH/NADCytoplasmic NADH/NAD+ Ratio
Affects activity of Glyceraldehyde 3-phosphate Affects activity of Glyceraldehyde 3-phosphate DehydrogenaseDehydrogenase Catalyzes reaction:Catalyzes reaction:
NADNAD++ is oxidized to NADH and H is oxidized to NADH and H++
Generated NADH can be re-oxidized to NADGenerated NADH can be re-oxidized to NAD++
Lack of NADLack of NAD++ will halt glycolysis will halt glycolysis Important for converting pyruvate into lactateImportant for converting pyruvate into lactate
Increase in ratio, through reduction, slows Increase in ratio, through reduction, slows glycolysisglycolysis
Decrease in ratio, through oxidation, speeds Decrease in ratio, through oxidation, speeds glycolysisglycolysis
Glycogen Phosphorylase (PHOS)Glycogen Phosphorylase (PHOS)
Glycogen is the primary source of G6-P to fuel Glycogen is the primary source of G6-P to fuel glycolysisglycolysis
Breakdown of glycogen is dependent on the Breakdown of glycogen is dependent on the PHOS enzymePHOS enzyme
Controlled through proportion of enzyme in the Controlled through proportion of enzyme in the active GPa form vs. inactive GPb formactive GPa form vs. inactive GPb form
Calcium Ion (CaCalcium Ion (Ca2+2+))
Regulates glycogen catabolismRegulates glycogen catabolism
Conversion of PHOS b (inactive) to PHOS a Conversion of PHOS b (inactive) to PHOS a (active) depends on stimulation of glycogen (active) depends on stimulation of glycogen phosphorylase kinase (GPK) by Caphosphorylase kinase (GPK) by Ca2+2+
Fast PHOS activationFast PHOS activation CaCa2+2+ released from sarcoplasmic reticulum immediately released from sarcoplasmic reticulum immediately
when muscles contractwhen muscles contract 4 Ca4 Ca2+2+ bind to calmodulin (subunit of GPK) to activate it bind to calmodulin (subunit of GPK) to activate it Active calmodulin can phosphorylate phosphorylase b Active calmodulin can phosphorylate phosphorylase b
to make it phosphorylase ato make it phosphorylase a
EpinephrineEpinephrine
Released when you are aroused or anxious Released when you are aroused or anxious before competitionbefore competition
Mediates stimulation of glucose production by Mediates stimulation of glucose production by the liver in advance of muscular uptakethe liver in advance of muscular uptake
Slow PHOS activationSlow PHOS activation Epinephrine binds to its Epinephrine binds to its ββ adrenergic receptor on adrenergic receptor on
skeletal muscleskeletal muscle Starts cascade of activation eventsStarts cascade of activation events Results in conversion of PHOS b to PHOS aResults in conversion of PHOS b to PHOS a