Please enable JavaScript.

Coggle requires JavaScript to display documents.

Glycolysis + PDH Complex - Coggle Diagram

- - - - Gluconeogenesis
    - - e.g. during strenuous exercise
      - Some tissues e.g. heart are adapted for aerobic performance
        
        Damaged in ischemic conditions
  - - - 2 x pyruvate
        
        2 x lactate
        
        Diffuses into bloodstream
        
        Liver
        
        Glucose production
        
        2 x NADH
        
        2 x NAD+
        
        NAD+ regeneration
        
        Intracellular pH drops
        
        Cramps
      - 2 x ADP
        
        2 x ATP
        
        Substrate level phosphorylation
        
        Generation of energy-rich phosphate bond by breakdown of more energy-rich substrate
      - 2 x NAD+
        
        2 x NADH + 2 x H+
  - - - Stage 1
        
        Energy investment
        
        Steps 1 - 5
      - Stage 2
        
        Energy generation
        
        Steps 6 - 10
  - - - 2 x Pyruvate
    - - 2 x ATP
    - - 2 x NADH
- - - - Un-complexed ATP is a competitive inhibitor
    - - Brings substrates together
    - - Inhibited allosterically by glucose-6-phosphate (G6P)
    - - Hexokinase
        
        Low Km, high affinity for glucose
        
        Non-specific, phosphorylates all hexoses
        
        Present in tissues, supply glucose to tissue even with low blood glucose
        
        Insulin independent
        
        Inhibited by G6P
      - Glucokinase
        
        High Km, low affinity for glucose
        
        Specific, only binds glucose
        
        Stimulated by insulin + glucose
        
        Only present in liver
        
        Removes glucose after eating
        
        Not inhibited by G6P
  - - - Phosphoglucose/phosphohexose isomerase
      - Specific to G6P/F6P
  - - - Phosphofructokinase-1
        
        Complex, various allosteric inhibitors/activators
        
        ATP is allosteric inhibitor
        
        Fructose-2,6-bisphosphate is activator
        
        Citrate is an inhibitor
        
        ADP + AMP are activators
  - - - Aldolase
      - Aldol condensation mechanism
      - Cleavage of FBP
    - - Reaction driven forward by later 2 reactions
  - - - Triose phosphate mutase
      - Acid-base catalysis
        
        His-95 and Glu-165 of enzyme involved
  - - - GAPDH
    - - Oxidising agent
  - - - By substrate-level phosphorylation
    - - Phosphoglycerate kinase
      - Proximity effect catalysis
      - ADP-Mg + 1,2BPG bind n 2 diff domains
        
        Conformational change brings them close
  - - - Phosphoglycerate mutase
        
        Phosphorylated at His-179 in active form
        
        Enzyme bound 2,3-BPG intermediate
        
        Occasionally observed in reaction mixture
      - In final step, phosphoryl group from C-3 of intermediate is transferred to enzyme + 2-PG released
    - - Regulation of O2 affinity to Hb
  - - - Enolase
      - Rapid proton extraction from C-2 position by general base
        
        Generation of carbanion
        
        Extracted proton readily exchanges with solvent
    - - Elimination of hydroxyl (OH) group
        
        PEP produced
  - - - Substrate-level phosphorylation
    - - Pyruvate kinase
      - Couples free E of PEP hydrolysis to ATP synthesis
      - Mg2+ and K+ needed
- - - - 5.2% total energy
- - - - Glucose - G6P
    - - Fructose-6-phosphate to fructose-1,6-BP
  - - - Converts G6P to glucose + fructose-1,6-BP
        
        Fructose-1,6-BP converted to F6P
- - - - Inhibits conversion of G3P to 1,3-BPG
  - - - During conversion of 1,3-BPG to 3-PG
  - - - Inhibits conversion of 2-phosphoglycerate to phosphoglycerate
- - - - When [substrate] and [product] are near equilibrium
    - - When [substrate] and [product] are far from equilibrium
      - Control flux of overall pathway
        
        Flux = rate of molecule turnover
      - 3 steps containing enzymes that control glycolysis flux
        
        Hexokinase
        
        Phosphofructokinase
        
        Pyruvate kinase
- - - - Generation of active 2C fragment
        
        Acetyl group of acetyl-CoA
  - - - Oxidative decarboxylation
        
        Add coenzyme A
        
        Acetyl CoA
        
        Containing 2 carbons
        
        Enters TCA/citric acid/Kreb's Cycle
        
        Released as CO2
        
        NAD+
        
        NADH
    - - 3 enzymes
        
        E1 - pyruvate dehydrogenase component
        
        Catalyses oxidative carboxylation of pyruvate
        
        Rate-limiting step
        
        E2 - dihydrolipoyl transacetylase
        
        Catalyses transfer of acetyl group to CoA
        
        Lipoamide
        
        E3 - dihydrolipoyl dehydrogenase
        
        Catalyses regeneration of oxidised form of lipoamide
      - 5 coenzymes
        
        Thiamine pyrophosphate
        
        Lipoic acid
        
        FADH2
        
        NADH
        
        CoA
      - Giant, elaborate structure
        
        Allow groups to travel from one active site to another
        
        Connected by tethers to structure core