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I know that oxaloacetate cannot cross the mitochondrial membrane, but can instead be converted to aspartate, shuttled out, and then re-converted back to oxaloacetate. What does this have to do with gluconeogenesis?

The traditional route is to convert pyruvate to OAA to malate in the mitochondria, shuttle the malate out, and then convert malate back to OAA in the cytosol. If lactate is the precursor, then the conversion of lactate to pyruvate in the cytosol can generate an NADH, making the conversion to malate in the mitochondria unnecessary. Thus, OAA is converted directly to PEP in the mitochondria by mitochondrial PEPCK and shuttled out to the cytosol to begin gluconeogenesis.

If we have these two pathways, what is the point of using aspartate?

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  • $\begingroup$ I think it is the other way round. Aspartate is pushed into the gluconeogesis pathway via OAA $\endgroup$ – WYSIWYG Feb 27 '15 at 4:53
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I may have approached this problem from the wrong direction, so here's my attempt at an answer:

For gluconeogenesis to function, glycolysis needs to be shut off. Glycolysis feeds the TCA cycle with Acetyl-CoA through the decarboxylation of pyruvate, and without glucose as a source, we need to look to other methods of generating OAA to make into PEP. We can make OAA through Aspartate Transaminase by reacting Aspartate with α-ketoglutarate.

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    $\begingroup$ Here's an excerpt from Oregon State. See the section titled "Spatial separation of gluconeogenesis metabolites." $\endgroup$ – CKM Feb 28 '15 at 18:02
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    $\begingroup$ Now, the answer to "Why is aspartate pervasive in cellular metabolism?" That's a particularly hard to answer, and my speculation, in part, is that this was simply how the system evolved. We see aspartate participate and act as a precursor to many pathways, esp. in amino acid metabolsim, but not much data exists yet as to the "why" of it all. $\endgroup$ – CKM Feb 28 '15 at 18:10

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