the old "fat burns in the flame of carbohydrate"

[LisaS]

so I was having a conversation with someone about the old saw "fat burns in the flame of carbohydrate" -- and it struck me - what is this referring to anyway (traditionally)?

the only thing I could think of was OOA limiting the TCA cycle - that is, no matter how much acetyl-CoA you have, it won't drive TCA unless there is OOA to drive things forward

I know pyruvate can be used to make OOA - so is that the CHO-dependent step that everyone is on about?

but still - the glycerol from the TAGs becomes glucose, right? and glycolysis will make pyruvate which will then favor OOA creation, right?

so - glucose is needed for TCA (more or less) but it doesn't have to be dietary carbohydrate - right?

so when my conversation-mate insists on dietary carbs being required to burn fats - it's a little off-base, right? glucose is needed for the eventual synthesis of OOA (is there another pathway to synthesize OOA ?) - but that could come from either dietary glucose or gluconeogenesis right?

or am I mis-remembering my basic biochem (its been 3 or 4 years)

[Gabriel Guzman]

so I was having a conversation with someone about the old saw "fat burns in the flame of carbohydrate" -- and it struck me - what is this referring to anyway (traditionally)?

the only thing I could think of was OOA limiting the TCA cycle - that is, no matter how much acetyl-CoA you have, it won't drive TCA unless there is OOA to drive things forward


Yep. Biochemically speaking, on a diet that has plenty of carbohydrates, Acetyl CoA (since you're using quite specific names of the intermediates of the Krebbs cycle, I will assume that you know that Acetyl CoA is) combines with OOA, which is one could say a by-product of carbohydrate metabolism. That's how Acetyl CoA enters the cycle to produce energy. So, just like you said, the limiting factor is OOA; if there is not enough OOA Acetyl CoA can't enter the cycle to be 'burned'. But OOA can also be made from Pyruvate, which in turn can be made from non-carbohydrate precursors such as Alanine. The same enzyme complex that turns Pyruvate into Acetyl CoA, also turns Pyruvate into OOA but for the latter to happen, Acetyl CoA needs to be in excess, which is what happens normally when there is increased fat oxidation. So, in a sense, OOA can also be a by-product of fat metabolism.


I know pyruvate can be used to make OOA - so is that the CHO-dependent step that everyone is on about?


If OOA is made from non-glycolytic Pyruvate, then that is not CHO-dependent. In the presence of excess of Acetyl CoA, Pyruvate can and will be used to make OOA. Even Pyruvate need not come from from glucose metabolism either since it can be made from Alanine.


but still - the glycerol from the TAGs becomes glucose, right?


It doesn't really become glucose but it is one of the main fuels for gluconeogenesis. OOA can also be used in gluconeogenesis. Glycerol enters the gluconeogenic pathway as glycerol-3-phosphate that's converted into dihydroxyacetone-phosphate and OOA is converted into PEP, which in turn is converted into glyceraldehyde-3-phosphate. Each one of these providing a 3-carbon skeleton that is further condensed into a six-carbon skeleton from which glucose is made after a few more steps.


...and glycolysis will make pyruvate which will then favor OOA creation, right?


Not necessarily. Pyruvate can also be made from Alanine so glycolysis is not an absolute requirement.


so - glucose is needed for TCA (more or less) but it doesn't have to be dietary carbohydrate - right?


Let's just say that Pyruvate is what is needed because, after all, Acetyl CoA is derived from pyruvate and glucose metabolism is not the only source of it. When you say 'it doesn't have to be dietary carbohyrate...' now that is the right context in our case. The fact that OOA can be generated from glucose metabolism, doesn't necessarily mean it can't be made from other sources as explained above.

What is more important to understand is that all these processes are exquisitely regulated by hormones. Sure enough, when there is little dietary carbohdyrate, to the point that the insulin:glucagon ratio is low, glucagon influences a number of processes including increasing fat oxidation (which increases Acetyl CoA), the expression of enzymes that are use to utilize amino acids (for example to make Pyruvate) and increase in the production of intermediates for gluconeogenesis. While that happens, glycolysis (opposite of glyconeogenesis) is pretty much shut down as well as fat synthesis (opposite of fat oxidation), otherwise we would end up with futile cycles everywhere.


so when my conversation-mate insists on dietary carbs being required to burn fats - it's a little off-base, right?


Yeah... a little bit...;)


glucose is needed for the eventual synthesis of OOA (is there another pathway to synthesize OOA ?) - but that could come from either dietary glucose or gluconeogenesis right?


Remember that OOA can be recycled and made from other sources. In the event of little dietary carbohdyate, which doesn't make glucose too available, OOA can be made from other sources such as Pyruvate, which in turn can be made from Alanine. So, what's really needed is Pyruvate regardless of where it comes from. If Acetyl CoA is in excess, as it normally happens when there is increase fat oxidation (common occurrence in carbohydrate-controlled diets), pyruvate is used to make OOA. If there is glucose around, then pyruvate produced by glycolysis will be the precursor of Acetyl CoA.


or am I mis-remembering my basic biochem (its been 3 or 4 years)

I'd say you did quite well... here's a gold star!:)