Carbohydrates, Glycolysis/Gluconeogenesis, and TCA

Carbohydrates, Glycolysis/Gluconeogenesis, and TCA

1. Carbohydrates

   • Have generic formula Cn(H20)n
   • Functions
     • Energy source and storage
     • Structural component
     • Informational molecules in cell-signaling
   • Structures to know
     • Glyceraldehyde
       • Triose sugar
     • Ribose
       • 5 carbon sugar, aldose, all OH's on the right
     • Mannose
       • C2 epimer of glucose
     • Glucose
     • Galactose
       • C3 epimer of glucose
     • Fructose
       • ketose sugar
     • Maltose
     • Cellobiose
     • Lactose
     • Sucrose
     • Cellulose
       • polymer of cellobiose
     • Chitin
     • Starch
       • has alpha 1-->6 brances every 20 residues
     • Glycogen
       • Branching alpha 1-->6 linkages about every 10 residues This allows rapid mobilization of glucose when needed

2. Glycolysis

   • Glucose is good fuel, can be stored in polymeric form
   • Versatile biochemical precursor
   • Can be stored as starch or glycogen
   • Short term energy needs met by glycolysis
   • Pentose phosphate pathway generates NADPH
   • Structural polysaccharides made from glucose
   • Hexokinase
     • Phosphohexose Isomerase
       • Phosphofructokinase
         • Aldolase
           • Triose Phosphate Isomerase
             • GAP Dehydrogenase
               • Phosphoglycerate Kinase
                 • Phosphoglycerate Mutase
                   • Enolase
                     • Pyruvate Kinase
                       • Acetyl CoA and TCA Cycle
                       • Lactate (anaerobic respiration)
                       • Fermentation (alcohols)
   • Key regulatory steps: 1, 3, 10 these steps are irreversible and have different enzymes in gluconeogenesis
   • Occurs mainly in the muscle and brain

3. TCA

   • Pyruvate dehydrogenase complex
     • Made up of E1 (pyruvate dehydrogenase), E2 (dihydrolipoyltransacetylase), and E3 (dihydrolipoyldehydrogenase). They are associated together to help prevent intermediates from being diffused away.
     • Citrate synthase
       • Aconitase
         • Isocitrate dehydrogenase
           • a-Ketoglutarate dehydrogenase
             • Succinyl-CoA Synthetase
               • Succinate Dehydrogenase
                 • Fumarase
                   • Malate dehydrogenase
   • 3 key steps are 2, 4, and 5
   • Anaplerotic reactions replenish the cycle
     • Channels reactants back into TCA

4. Regulation

   • One reaction in a pathway is almost always irreversible
   • Fatty acids can NOT be used for gluconeogenesis
   • Gluconeogenesis occurs mainly in the liver and kidneys
   • Steps 1,3, and 10 of gluconeogenesis are different than glycolysis
   • Very expensive but necessary since the brain, nervous system, and blood cells can only generate ATP from glucose
   • Lactate can be recycled in the liver and reoxidized to pyruvate which can be used in gluconeogenesis
   • When glycolysis is turned on, gluconeogenesis is off, and vice versa
   • When energy is low (large [AMP]) cell goes into glycolysis, when energy is high (large[ATP]) the cell goes into gluconeogenesis
   • Muscles consume glucose for energy production, liver maintains blood glucose homeostasis by removing or producing glucose depending on conditions
   • Insulin
     • Released from pancreas in response to increased glucose in blood
   • Glucagon
     • Released by pancreas in response to low blood glucose
     • Active on liver and adipose tissue but NOT muscle and brain
       • Epinephrine works on liver and muscles
     • Stimulates liver to release glucose from glycogen stored in blood
   • Regulation of fructose 2,6-bisphosphate
     • Fructose 2,6-bisphosphate is formed by PFK-2 and not formed by FBPase 2, F26BP inhibits FBPase-1 and gluconeogenesis and activates PFK-1 and glycolysis in high concentrations, activates FBPase-1 and gluconeogenesis and inactivates glycolysis in low concentrations

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