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L6 Glycolysis (Glycolysis
Glycose = sweet, lysis = to break : conversion…
L6 Glycolysis
Glycolysis
- Glycose = sweet, lysis = to break : conversion of glucose into pyruvate
- Maj pathway of glucose catabolism
- Unique: can function aerobically or anaerobically, depending on O2 availability & intact mitochond, thus allows tissues to survive in O2 presence or absence, e.g sk muscle
- RBC lack mitochond, so reliant on glucose as fuel metabolised by anaerobic glycolysis
- Provides E in form of ATP
- In norm circumstances glucose is the only fuel the brain (CNS) can use
- Glucose is also preferentially used by muscle
Phosphorylation - necessary for glucose to enter glycolytic pathway
- Add a phosphate grp twice to that
- Add a P grp & we've trapped tht glucose in the (C)
~ & traps glucose in (C), no transmembrane carriers & phosphorylated sugars can't cross (C) memb (too polars)
- First stage of aerobic carbs metabolism
~ Glucose ⇒ pyruvate in cytosol
~ 10 step chain (linear pathway)
- Glycolysis can occur in absence of O2 (anaerobic metabolism) glucose ⇒ lactate (later) if we don't have O2 around
2 Main Phases
- Remember: st of pyruvate!
- catabolic pathways = ATP is made
- catabolicm: breaking down the food we eat, but direct reactons of ATP from ADP is anabolic, the total pathway of breaking down the food we eat is catabolic to produce ATP
- 1) Preparatory: 6C glucose is split into 2x 3C triose-P
~ 5 step process (input)
- 2) Payoff: Triose-P is oxidised to pyruvate
~ 5 step process (net ATP & NADH generate)
Respiration: Step 1 Glycolysis
- complete breakdown of glucose into CO2 + H2O
- can undergo glycolysis even if there's no O2
-1x molec of glucose (6C) broken down to 2x molecs of pyruvate (3C)
- E yield = 2x ATP & 2x NADH (e- carrier)
~ used to do (C)ullar work within the body
-
Some key reaction types
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Redox reactions - dehydrogenase (GAPDH)
- GAPDH = glyceraldehyde 3P dehydrogenase
- Can involve simply e- transfer or can involve transfer of H (as in NADH)
NADH
- (C)ullar currency of reductive Ep & is produced during respiration... is a cosubstrate, a temporarily-bound coezm
- In dehydrogenation: removing the H, 2e- plus that proton, to give NADH
- Reaction proceeds in 2 steps, forming an intermediate linked to GAPDH by a thioester bond (high E), which preserves much of the oxidation rxn E for subsequent phosphorylation to give 1,3-BPG (coupling unfavourable & favourable rxns)...
- Understand that process of oxidation
Substrate-lvl phosphorylation - Kinase
Phosphoglycerate kinase = PGK
- 1,3-BPG is E-rich (essentially traps the E of GAPDH's oxidation rxn) w/ a high P-transfer potential, so can power ATP synth from ADp
- This is substrate-lvl phosphorylation as 1,3-BPG (the substrate) has the P-tranfer potential
Phase 1
- = Ezms:
- Hexokinase :star:
- Phosphoglucose isomerase
- Phosphofructokinase :star:
- :star: (where the process of ezm is regulated, irreversible, the rest of the ezms are driven in that reaction bc of these main 3)
- Aldose
- Triose phosphate isomerase
- All subsequent reactions occur twice, have 2x Glyceraldehyde 3P, each 3C
Preparatory phase
Phosphorulation of glucose and its conversion to glyceraldehyde 3-(P)
- 1) Hexokinase: Some of our (C) have an isoezm called a glucokinase: same function- one of the hexokinase
- 2) Phosphohexose isomerase
- 3) Phospho- fructokinase-1 : the main reg ezm in the whole pathway
- 4) Aldolase
- 5) Triose phosphate isomerase
All subsequent reactions occur twice
- have 2x Glyceraldehyde 3(P), each 3C
Phase 2
- =Ezms
- Glyceraldehyde 3P dehydrogenase
- Phosphoglycerate kinase
- Phosphoglycerate mutase
- Enolase
- *Pyruvate kinase
Payoff Phase
Oxidative conversion of glyceraldehyde 3 (P) to pyruvate & the coupled formation of ATP and NADH
- 6) Glyceraldehyde 2-phosphate dehydrogenase
- 7) Phosphoglycerate kinase : can now be used to anabolically form ATP to ADP bc of those (P)s, the ADPstrips one of the (P) to give phosphohlycerate & 2ATP- now we've paid back to the (C) bc used 2x ATP & made 2
- 8) Phosphoglycerate mutase
- 9) Enolase- gaining a water molec in our cytoplasm
- 10) Pyruvate kinase
Free E changes (∆G) in glycolysis (RBC)
- All reactions are essentially reversible, except those catalysed by: 3 reactions
1) # hexokinase
2) oPhosphofructokinase
3) pyruvate kinase
- These 3 steps steps are essentially irreversible, large -ve ∆G, providing driving force for glycolysis
- Reactions are never really equilibrium in our bodies
- The other ones are kinda neutral
- several isozymes of hexokinase, in liver & pancreatic islet (C)s have glucokinase
3 main points of glycolysis regulation
- Hexokinase
~ -ve reduce the activity: turn off hexokinase: feedback inhibition: if we have high levels of glucose
~ if the (C) has lots of inorganic phosphates the (C) will have low ATP: can drive the activity of hexokinase
- Phosphofructokinase
~ Since there is diff isozyme distribution, not all body tissues have all regulatory mechs shown
- Pyruvate kinase
~ can be activated by feed forward syst
~ high lvl of ATP: switch off activity of pyruvate kinase
~ Bc role of glycolysis is to make ATP, if have enough, (C) won't waste time making more = control
Phosphofructokinase (PFK) = most important control site for our glycolytic pathway
- PFK = tetramer
- High [ATP] allosterically inhibit PFK (what?)
- AMP reverses inhibits (low [ATP], when high [AMP])
- pH drop also inhibits PFK- important in anaerobic metabolism (later)
-
Learning Outcomes
- Understand the importance of glycolysis, what substrates are involved & what the pathway is used for.
- Describe the loc and reactions of glycolysis and the mech of E
- Be able to give the reactions using and producing ATP and NADH and know their net overall yields
- Explain the diff between reversible & irreversible reactions
Understand the regulation of the glycolytic pathway, & which ezms are regulated