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NADH (‘reduced NAD’) is produced during the oxidation of blood lactate in the liver. Glycolysis requires NAD+ (‘oxidised NAD’), whereas gluconeogensis requires NADH. However the NADH is apparently not always used for gluconeogenesis (How is NAD+ used in lactic acid fermentation after it is oxidized from NADH?), i.e. the Cori Cycle does not always operate — so what becomes of the NADH in this case?

My best guess is that, along with the pyruvate, it may be transferred in the blood somehow to do to the site where it is needed, and it will then be taken into the electron transport chain, while the pyruvate will be taken into the Krebs cycle.

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  • $\begingroup$ I have condensed your question to make it clearer. If I have altered your meaning please say so. $\endgroup$
    – David
    Mar 13, 2017 at 22:45

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The “best guess” in this question is incorrect and the question itself indicates a lack of understanding of the roles of NAD+ and NADH in energy metabolism. (To rectifiy this, Chapters 17 and 18 of Berg et al. are suggested.)

The production of NADH in the oxidation of carbohydrates and fats is the energetic rationale for these processes. Under aerobic conditions the re-oxidation of NADH to NAD+ via the electron transport chain in the mitochondria* generates ATP for the energetic processes of the cell.

The fate of NADH produced by the oxidation of lactate reaching the liver from the blood would be similar under conditions where it is not needed for gluconeogenesis (in the reversal of the GAPDH reaction). In these circumstances it would be reoxidized to NAD+, generating ATP in the mitochondria*.

[Note also that pyruvate is most likely to be oxidized by the liver mitochondria to produce metabolic intermediates and ATP, rather than transferred to the blood. NADH is certainly not transferred to the blood.]

*Advanced Point: Cytoplasmic and Mitochondrial NAD

The statement above, that NADH is “reoxidized to NAD+, generating ATP in the mitochondria”, is correct, but may be taken to imply that the NADH enters the mitochondria. This is not the case becase the NADH and NAD+ cannot pass through the mitochondrial membrane (as @tomd has commented). However the electrons that represent the reduced state of NADH do pass through the membrane. They do this in the guise of other molecules which are reduced in the cytoplasm by NADH in what are known as electron shuttles. The electrons enter the electron transport chain and are finally accepted by molecular oxygen. More detail of shuttles can be found in section 18.5 of Berg et al.

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  • $\begingroup$ @tomd — Thank you for that elaboration but the question was not about NAD transport (or effective) transport across the mitochondrial membrane. Including it in my answer would have reduced its clarity and obscured the basic principle of what the NADH is used for. $\endgroup$
    – David
    Mar 13, 2017 at 12:33
  • $\begingroup$ @tomd — I have now modified the question, the first paragraph of my answer, and added a footnote about shuttles. I trust this incorporates the points you raised. $\endgroup$
    – David
    Mar 13, 2017 at 23:26

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