Metabolism
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How is NADH from glycolysis normally re-oxidised?
Key points from this exercise:
NADH formed in the cytosol cannot enter mitochondria to undergo re-oxidation in the electron transport chain.
There are two substrate shuttles that transfer reducing equivalents from cytosolic NADH into the mitochondrion:
The malate-aspartate shuttle, in which :
aspartate from the mitochondria crosses to the cytosol.
aspartate is transaminated (at the expense of ketoglutarate) to yield oxaloacetate
oxaloacetate is reduced to malate by cytosolic NADH
malate enters the mitochondrion and is oxidised to oxaloacetate, yielding NADH inside the mitochondrion
oxaloacetate is transaminated to aspartate, which leaves the mitochondrion.
The glycerol phosphate shuttle, in which
dihydroxyacetone phosphate (a glycolytic intermediate) is reduced to glycerol 3-phosphate in the cytosol, and enters the mitochondria
in the mitochondrion glycerol 3-phosphate is oxidised to dihydroxyacetone phosphate, at the expense of reducing FAD to FADH2. Dihydroxyacetone phosphate then leaves the mitochondrion, back into the cytosol.
The glycerol phosphate shuttle is energetically less efficient than the malate-aspartate shuttle, because the FADH2 formed inside the mitochondrion yields only ~1.5 x ATP in the electron transport chain, while the NADH formed in the malate-aspartate shuttle yields ~2.5 x ATP in the electron transport chain.
The capacity of the malate-aspartate shuttle is limited, and it cannot operate fast enough to meet the need to re-oxidise all of the NADH formed in tissues with a high rate of glycolysis, so there is a need for the less efficient, but faster, glycerol 3-phosphate shuttle.