The picture is from my lecture note.

My teacher taught me in a lecture that PEP forms from Pyruvate by two ways, based on their sources, that is - 1. If the Pyruvate was from lactate (by lactate dehydrogenase action), it gets shuttled into mitochondria and is successively converted to OAA and PEP, by enzymes PC and PEPCK(mitochondrial) respectively. This PEP is then shuttled to cytosol for rest of gluconeogenic steps to take place. 2. Whereas, if the Pyruvate was from any other source, it is shuttled to the mitochondria, where it is converted to OAA by PC. It is then shuttled to cytosol by malate shuttle and then converted to PEP by PEPCK (cytosolic). Why the difference in mechanism? Please correct me if any of these steps are wrong.

  • $\begingroup$ I think that (i) The LDH reaction in 'backwards' (it should be pyruvate +NADH + H(+) = lactate + NAD(+). LDH dehydrogenates lactate but reduces pyruvate). (ii) Note that PC used CO(2) (as bicarbonate), an example of CO2 being 'fixed' in a heterotrophic system (very controversial at one time $\endgroup$ – user1136 Nov 20 '18 at 9:02
  • $\begingroup$ Thanks for the corrections. But my main doubt was that why does the Pyruvate from lactate follow a different way to become PEP rather than the other way (when Pyruvate is produced from other sources), or vice versa. The question could also be framed this way - 'why does two mechanisms exist for conversion of Pyruvate to PEP?' Thanks. $\endgroup$ – Adith Krishna Nov 20 '18 at 11:22
  • $\begingroup$ What is the basis of the right portion of your diagram which is new to me? The vast majority of the PEP used for gluconeogenesis is generally thought to occur in the cytoplasm from oxaloacetate made in the mitochondrion and shuttled out via malate as indicated in the left of your diagram. Even though there is evidence for a mitochondrial PEPCK, this has no known role in gluconeogenesis. Even if it did, how could it distinguish pyruvate from different sources? $\endgroup$ – David Nov 20 '18 at 13:55
  • $\begingroup$ In any case, please rewrite your question so that your diagram is only an illustration of the text. The question should not rely on text on an image as it is not possible to index it and it discriminates against people with sight problems. You can do this by carefully describing the key steps in words. Please quote the source for your diagram or explain if it is from notes taken at a lecture. $\endgroup$ – David Nov 20 '18 at 14:01
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    $\begingroup$ Sorry mate. Did not think of that while posting the diagram. The diagram and source of the content was from a biochemistry lecture. But, I found other sources (like this one: ncbi.nlm.nih.gov/m/pubmed/24497630) where mitochondrial PEPCK was linked to lactate (Here, silencing of mit. PEPCK in rats was seen to increase lactate and lower plasma glucose). Thanks. $\endgroup$ – Adith Krishna Nov 20 '18 at 15:11

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