so is it fair to say that in the mitochondria that oxaloacetate gets pushed to malate which is "kind of" facilitating gluconeoegenesis, but then you get a big flux of malate out into the cytosol where it can't be converted back to oxaloacetate.Couple points 1. The conversion of lactate to pyruvate is inhibited (high NADH inhibits this). Indeed the high NADH actually drives pyruvate to lactate. So you are decreasing that substrate. 2. Oxaloacetate must be converted to Malate to get to the cytosol the Malate dehydrogenase works at this step and the conversion of Malate back to oxaloacetate in the cytosol and NAD is required for this enzyme and NADH inhibits it. My understanding is that point 1 is the major mechanism and point 2 further reinforces it. FA is confusing/wrong? About this on that page. (I personally think Biochem is unfortunately FA's weakest chapter). Anyway hope that helps. As a side note EtOH metabolism doesn't affect glycogenolysis so that is why you can maintain a normal glycemic state for awhile until it falls. As another note the increase in NADH favors the conversion of acetyl coa that is around to lipogensis (fatty liver, the NADH inhibits isocitrate dehydrogenase and alpha ketogluterate dehydrogenase) and ketone production and inhibits beta oxidation as the point of that is the production of NADH. Hope that helps
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so is it fair to say that in the mitochondria that oxaloacetate gets pushed to malate which is "kind of" facilitating gluconeoegenesis, but then you get a big flux of malate out into the cytosol where it can't be converted back to oxaloacetate.
I'm still struggling to understand ketones for some reason. FA says that the acetyl coA that's around gets shunted to ketogenesis. Where is this acetyl coA coming from if pyruvate is getting shunted to lactate and pyruvate dehydrogenase is probably inhibited itself by the high NADH.. so how is acetyl coa being produced to shunt to ketogenesis?
Pretty simple, look at the big picture:
Oxaloacetate is the oxidized form.
Malate is the reduced form.
For OAA ----> Malate (you need more NADH:the reducing agent: which is present, so this reaction will be favored)
For Malate ----> OAA (you need more NAD+:the oxidizing agent: which is not present, so this reaction will not be favored)
As a result, you can generate as much Malate as you want but you can't generate OAA at all. Whatever OAA is there is being converted to Malate. No OAA is available to be converted to Phospoenolpyruvate. Hence, gluconeogenesis can't happen (meaning it's inhibited).
