Glycolysis Rxn 1: enzyme & class Hexokinase Transferase Glycolysis Rxn 2: enzyme & class Phosphoglucose isomerase Isomerase Glycolysis Rxn 3: enzyme & class Phospofructokinase (PFK-1) Transferase Glycolysis Rxn 4: enzyme & class Aldolase Lyase Glycolysis Rxn 5: enzyme & class Triose phosphate isomerase Isomerase Glycolysis Rxn 6: enzyme & class Glyceraldehyde-3-Phosphate dehydrogenase Oxidoreductase Glycolysis Rxn 7: enzyme & class Phosphoglycerate kinase Transferase Glycolysis Rxn 8: enzyme & class Phosphoglycerate mutase Mutase Glycolysis Rxn 9: enzyme & class Enolase Lyase Glycolysis Rxn 10: enzyme & class Pyruvate kinase Transferase Glycolysis Rxn 1: reactant -> product & rxn type Glucose -> Glucose-6-Phosphate -Phosphorylation Glycolysis Rxn 2: reactant -> product & rxn type Glucose-6-Phosphate -> Fructose-6Phosphate -Aldose-Ketose interconversion Glycolysis Rxn 3: reactant -> product & rxn type Fructose-6-Phosphate -> Fructose-1,6Bisphosphate -Phosphorylation Glycolysis Rxn 4: reactant -> product & rxn type Fructose-1,6-Bisphosphate -> Dihydroxyacetone Phosphate (DHAP) + Glyceraldehyde-3-Phosphate -Reverse aldol condensation Glycolysis Rxn 5: reactant -> product & rxn type Dihydroxyacetone Phosphate (DHAP) -> Glyceraldehyde-3-Phosphate -Ketose-Aldose interconversion Glycolysis Rxn 6: reactant -> product & rxn type Glyceraldehyde-3-Phosphate -> Glycerate1,3-Bisphosphate -1) oxidation -2) phosphorylation Glycolysis Rxn 7: reactant -> product & rxn type Glycerate-1,3-Bisphosphate -> 3Phosphoglycerate -Substrate level phosphorylation Glycolysis Rxn 8: reactant -> product & rxn type 3-Phosphoglycerate -> 2-Phosphoglycerate -Isomerization Glycolysis Rxn 9: reactant -> product & rxn type 2-Phosphoglycerate -> Phosphoenolpyruvate (PEP) -Dehydration Glycolysis Rxn 10: reactant -> product & rxn type Phosphoenolpyruvate (PEP) -> Pyruvate -Substrate level phosphorylation Glycolysis Rxn 1: purpose Starts destabilization by phosphorylating glucose to make it glucose-6-P. Phosphorylation by hexokinase traps glucose within the cell for metabolism and allows more glucose to enter the cell. Glycolysis Rxn 2: purpose Conversion of secondary alcohol to a primary alcohol, making molecule more symmetrical in preparation of splitting it into two 3-carbon pieces. Glycolysis Rxn 3: purpose 1. Phosphorylation such that both 3-carbon pieces will be retained in the cell 2. Committing molecules to glycolysis so once initiated, molecule will finish glycolysis (main regulation step) Glycolysis Rxn 4: purpose To create two 3-carbon pieces Glycolysis Rxn 5: purpose Conversion to glyceraldehyde-3-P makes both molecules DHAP carbons Glycolysis Rxn 6: purpose Making an energy rich molecule (glycerate-1,3-BP) for substrate level phosphorylation Glycolysis Rxn 7: purpose To make ATP Glycolysis Rxn 8: purpose Moving phosphate from C3 to C2 helps set up for PEP formation Glycolysis Rxn 9: purpose Production of energy rich PEP which sets up for substrate level phosphorylation Glycolysis Rxn 10: purpose 1. To make pyruvate 2. To make ATP Glycolysis Energy investment rxns Rxn 1: 1 ATP/glucose Rxn 3: 1 ATP/glucose Glycolysis Energy payoff rxns Rxn 7: 2 ATP/glucose Rxn 10: 2 ATP/glucose Glycolysis ATP net gain 2 ATP/glucose Glycolysis Irreversible rxns Reactions 1, 3 and 10 are irreversible, therefore, they are the regulated steps Glycolysis Rxn 1 regulation Inhibitors: 1) Glc-6-P: product inhibition 2) ATP: high levels indicate that cellular energy is high Glycolysis Rxn 3 regulation: Activators 1) AMP: indicates low cellular energy 2) Frc-2,6-BP: allosteric regulator produced by a bifunctional enzyme (F-2,6-BPase/PFK2). Buildup of Frc-2,6-BP causes activation of Frc-2,6-BPase, which makes more Frc-6-P for the rxn. Glycolysis Rxn 3 regulation: Inhibitors 1) ATP - high cellular energy 2) NADH - high cellular energy 3) Citrate - CAC intermediate Glycolysis Rxn 3 regulation: Hormonal control 1) glucagon -"glucose is gone" indicates low blood glucose -phosphorylates bifunctional enzyme -Frc-2,6-BPase activates -PFK-2 deactivates -glycolysis is inhibited 2) insulin -indicates high blood glucose -dephosphorylates bifunctional enzyme -Frc-2,6-BPase deactivates -PFK-2 activates -glycolysis is activated Glycolysis Rxn 10 regulation: Allosteric 1) ATP - Inhibits because indicates high cellular energy 2) Acetyl CoA - Inhibits because indicates high cellular energy and plentiful CAC intermediates 3) Frc-1,6-BP - Activates because of feed forward activation Glycolysis Rxn 10 regulation: Hormonal Glucagon - Inhibits - Causes phosphorylation of pyruvate kinase which leads to inhibition of enzyme Gluconeogenesis Bypass 1, Rxn 1: Enzyme & Class Pyruvate Carboxylase Ligase Gluconeogenesis Bypass 1, Rxn 2: Enzyme & Class PEP Carboxykinase Lyase Gluconeogenesis Bypass 2: Enzyme & Class Fructose-1,6-Bisphosphatase Hydrolase Gluconeogenesis Bypass 3: Enzyme & Class Glucose-6-Phosphatase Hydrolase Gluconeogenesis Bypass 1, Rxn 1: Reactant -> product & rxn type Pyruvate -> Oxaloacetate (OAA) -Carboxylation Gluconeogenesis Bypass 1, Rxn 2: Reactant -> product & rxn type Oxaloacetate (OAA) -> PEP -Decarboxylation and phosphorylation Gluconeogenesis Bypass 2: Reactant -> product & rxn type Fructose-1,6-Bisphosphate -> Fructose-6-Phosphate -Dephosphorylation Gluconeogenesis Bypass 3: Reactant -> product & rxn type Glucose-6-Phosphate -> Glucose -Dephosphorylation Gluconeogenesis Bypass 1, Rxn 1: Regulation Allosteric 1) ADP - Inhibits - Indicates low cellular energy 2) Acetyl CoA - Activates - Fatty acid degradation, starvation conditions Gluconeogenesis Bypass 1, Rxn 2: Regulation Allosteric 1) ADP - Inhibits - Indicates low cellular energy Gluconeogenesis Bypass 2: Allosteric Regulation 1) AMP - Inhibits 2) Frc-2,6-BP - Inhibits 3) ATP - Activates 4) Citrate - Activates Gluconeogenesis Bypass 2: Hormonal Regulation 1) Glucagon -Bifunctional enzyme is phosphorylated -Favors degradation of Frc-2,6-BP -Gluconeogenesis is favored 2) Insulin -Bifunctional enzyme is dephosphorylated -Favors the production of Frc-2,6-BP -Glycolysis is favored Gluconeogenesis Bypass 3: Regulation Yes but complex and not well understood Glycogenesis Rxn 1: enzyme and class Hexokinase or Glucokinase Transferase Glycogenesis Rxn 2: enzyme and class Phosphoglucomutase Mutase Glycogenesis Rxn 3: enzyme and class UDP-Glucose Phosphorylase Transferase Glycogenesis Rxn 4: enzyme and class Glycogen Synthase Lyase Glycogenesis Rxn 5: enzyme and class Branching Enzyme Transferase Glycogenesis Rxn 1: reactant -> product & rxn type Glucose -> Glucose-6-Phosphate -Phosphorylation Glycogenesis Rxn 2: reactant -> product & rxn type Glucose-6-Phosphate -> Glucose-1Phosphate -Isomerization Glycogenesis Rxn 3: reactant -> product & rxn type Glucose-1-Phosphate -> UDP-Glucose -UDP transfer Glycogenesis Rxn 4: reactant -> product & rxn type Glycogenin Primer + UDP-Glucose -> Glycogenin + growing glycogen chain -Glycosylation Glycogenesis Rxn 5: reactant -> product & rxn type Growing glycogen chain -> Branched glycogen -Transferase Glycogenesis Rxn 1: purpose Starts destabilization of glucose by phosphorylating it. Phosphorylation of glucose also traps it inside the cell and allows more glucose to enter Glycogenesis Rxn 2: purpose Form a more reactive phosphosugar that will be used for glycosylation reactions Glycogenesis Rxn 3: purpose Further activation of glucose for glycosylation. UDP is a great leaving group. Glycogenesis Rxn 4: purpose Formation of alpha-1,4 linkage to new glucose, growing glycogen chain Glycogenesis Rxn 5: purpose To form a branched alpha-1,6 glycogen chain. Need a minimum of 4 alpha-1,4 linkages between each alpha-1,6 linkage Glycogenesis Rxn 1: regulation 1) Glc-6-P - product inhibition 2) ATP - Inhibition - indicates high cellular energy Glycogenesis Rxn 4: regulation (allosteric) 1) Glc-6-P - activator - plentiful precursors Glycogenesis Rxn 4: regulation (covalent) 1) glycogen synthase a - dephosphorylated = active 2) glycogen synthase b - phosphorylated = inactive 3) glycogen primer - Tyr-OH on glycogenin protein is autocatalytic. 4-8 glucoses are added to Tyr-OH before glycogen synthase can act Citric Acid Cycle Rxn 1: enzyme & class Citrate synthase Transferase Citric Acid Cycle Rxn 2: enzyme & class Aconitase Isomerase Citric Acid Cycle Rxn 3: enzyme & class Isocitrate dehydrogenase Oxidoreductase Citric Acid Cycle Rxn 4: enzyme & class alpha-Ketoglutarate Dehydrogenase Oxidoreductase Citric Acid Cycle Rxn 5: enzyme & class Succinyl CoA Synthase Ligase Citric Acid Cycle Rxn 6: enzyme & class Succinate Dehydrogenase Oxidoreductase Citric Acid Cycle Rxn 7: enzyme & class Fumarase Lyase Citric Acid Cycle Rxn 8: enzyme & class Malate Dehydrogenase Oxidoreductase Citric Acid Cycle Rxn 1: reactant -> product & rxn type Oxaloacetate (OAA) -> Citrate -Aldol condensation Citric Acid Cycle Rxn 2: reactant -> product & rxn type Citrate -> Isocitrate -Stereospecific dehydration and rehydration Citric Acid Cycle Rxn 3: reactant -> product & rxn type Isocitrate -> Oxalosuccinate -> alphaKetoglutarate -Oxidative decarboxylation Citric Acid Cycle Rxn 4: reactant -> product & rxn type alpha-Ketoglutarate -> Succinyl-CoA -Oxidative decarboxylation Citric Acid Cycle Rxn 5: reactant -> product & rxn type Succinyl CoA -> Succinate -Substrate level phosphorylation Citric Acid Cycle Rxn 6: reactant -> product & rxn type Succinate -> Fumarate -Dehydrogenation Citric Acid Cycle Rxn 7: reactant -> product & rxn type Fumarate -> Malate -Stereospecific hydration Citric Acid Cycle Rxn 8: reactant -> product & rxn type Malate -> Oxaloacetate (OAA) -Dehydrogenation Citric Acid Cycle Irreversible steps Reactions 1, 3, 4 Citric Acid Cycle Rxn 1: Substrate Regulation 1) Acetyl CoA - Activator 2) Oxaloacetate - Activator Citric Acid Cycle Rxn 1: Product Regulation 1) Citrate - Product inhibition Citric Acid Cycle Rxn 1: Allosteric Regulation 1) Succinyl CoA - Inhibitor - (negative feedback inhibition) 2) ATP - inhibitor - because cellular energy is high 3) NADH - inhibitor - because cellular energy is high Citric Acid Cycle Rxn 3: Allosteric Regulation 1) ATP - inhibitor 2) NADH - inhibitor 3) ADP - activator 4) NAD+ - activator 5) Ca2+ - activator Citric Acid Cycle Rxn 4: Product Regulation 1) Succinyl CoA - Product inhibition Citric Acid Cycle Rxn 4: Allosteric Regulation 1) ATP - inhibitor 2) NADH - inhibitor 3) ADP - activator 4) NAD+ - activator 5) Ca2+ - activator Citric Acid Cycle Rxn 1: Purpose Replenishing carbons lost as CO2 in last turn of the cycle Citric Acid Cycle Rxn 2: Purpose Convert unreactive tertiary alcohol to a more reactive secondary alcohol Citric Acid Cycle Rxn 3: Purpose Converting secondary alcohol to a ketone 1. oxidize carbon to CO2 2. make NADH for ETC/OP Citric Acid Cycle Rxn 4: Purpose 1. Oxidize carbon to CO2 2. Make NADH 3. Make energy rich molecule Citric Acid Cycle Rxn 5: Purpose 1. Make GTP 2. Make symmetrical molecule Citric Acid Cycle Rxn 6: Purpose 1. Place a strategic CC double bond 2. Make FADH2 Citric Acid Cycle Rxn 7: Purpose Add OH that will be oxidized in next step to make OAA Citric Acid Cycle Rxn 8: Purpose To make OAA ETC/OP Complex 1: molecules in & out In: NADH Out: CoQH2 ETC/OP Complex 1: molecules in & out In: FADH Out: CoQH2 ETC/OP Complex 1: molecules in & out In: CoQH2 Out: reduced CytC ETC/OP Complex 1: molecules in & out In: reduced CytC Out: 1/2 O2 (final electron acceptor)