Blood Constituents — ATP Generation

ATP Generation by mitochondia

• Mitochondria form ATP via oxidative phosphorylation (Major), via Kreb’s cycle and Electron transport chain (ETC)
• mitochon found in high conc in cells with high metabolic demands eg myocardium (23% of cell), brown fat (neonate)
• exercise ↑s numbers
• OP = production of ATP associated with oxidation by the flavoprotein cytochrome system in mitochondria
• Structure
  • The inner and outer membranes of mitochondria define three compartments within the organelle, each with its distinct role and corresponding protein components.
  • Outer membrane separates mitochondria from cytoplasm
  • The innermost compartment, surrounded by the inner membrane, is the mitochondrial matrix
  • The inner membrane of the mitochondrion contains the components of the electron transport chain.
  • The high pH of the mitochondrial matrix creates the trans-membrane electrochemical gradient that drives ATP synthesis
  • Oxidation/reduction reactions along the components of the electron transport chain generate a proton gradient that is used by ATP synthase to phosphorylate ADP, thereby producing ATP.
  • To increase the capacity of the mitochondrion to synthesize ATP, the inner membrane is folded to form cristae. These folds allow a much greater amount of electron transport chain enzymes and ATP synthase to be packed into the mitochondrion.

• Kreb’s cycle (TCA or citric acid cycle)
  • Carbohydrate / Protein / Lipid ⇒ Acetyl coenzyme A or other intermediates
  • Acetyl CoA ⇒ Kreb’s cycle

• Electron Transport Chain (ETC)
  • The metabolic pathway through which the electron passes, starting with one transporter and then onto the next, is known as the electron transport framework (ETS).
  • The electron transport framework happens in the inward mitochondrial layer.
  • The electron transport chain contains the accompanying:
    • Complex I: NADH dehydrogenase
    • Complex II: succinate dehydrogenase
    • Complex III: cytochromes bc 1
    • Complex IV: cytochromes a-a3
    • Complex V: ATP synthase

• ATP formed in electron transfer chain:
  • Substrate diffuses into mitochon cytoplasm
  • Hydrogen removed by a dehydrogenase
  • NAD carries hydrogen to respiratory chain
  • Hydrogen ionises and protons pass along series of carrier molecules across insulating membrane (inner membrane of mitochondria – forms cristae)
  • Movement of protons creates an electrochemical gradient for transport of protons from intermediate space back into matrix ⇒ this drives a reversible ATPase in inner membrane (ATP synthase)
  • ATP synthase: ADP + Pi ⇒ ATP
  • @end:
    • ATP produced
    • Reduction of O2 to water – catalysed by cytochrome oxidase
      • cyanide inhibits this oxidase ∴ inhibits OP in mitochon
    • O2 required to oxidise NADH
• Eg’s of carrier molecules in electron transfer chain
  • Flavoprotein
  • Cytochromes A, A3, B, C, C1
  • Ubiquinone
  • Several iron sulphide proteins
• OP depends on:
  • Adequate supply of ADP: +ve feedback loop e.g. ↑ATP utilisation ⇒ ↑ADP ⇒ ↑OP
  • Rate of delivery of fats, lactate, glucose to interior of mitochon
  • Availability of O2: Pasteur point = 1-2mmHg i.e. point below which OP cannot occur
• ∴ cardioresp works in harmony to ensure o2 reaches cells
  • defined by oxygen flux equation:

ATP Generation by RBCs

• RBC have no Mitochondia – Cannot perform aerobic metabolism
• All ATP is generated via anaerobic glycolysis (Embden-Meyerhof pathway / EMP) (90% glycolysis)
  • 10-step Catabolic pathway in cytosol
  • by degradation of glucose molecule
  • produces 2x ATP + pyruvate/lactate per glucose → ATP is used by Na+/K+ATPase, which is implicated in maintaining RBC shape, volume and flexibility
• Steps

• 3 shunts that come off the anaerobic glycolytic pathway (produce no ATP)
  • the Rapoport-Luebering shunt (BPG Shunt): 2,3-DPG is interconverted from 1,3-DPG (glycolytic intermediate)
  • Hexose monophosphate shunt (HMP shunt or pentose phosphate pathway) – generates NADPH – protects RBC from oxidative damage (10% glycosis)
  • NADH generated – used by MetHb reductase to reduce oxidised Hb (MetHb) to Hb