I looked into some of the rate limiting steps involved in Gluconeogenesis for the “Steak therefore Cake” post;
I don’t think anyone has taken a theory of constraints approach to energy biochemistry as a system. You might be right there may be a fertile territory there.
Those are all intriguing questions.
I’m going to try answer some (and a few you didn’t ask) using my intuited synthesis (with a few references for the bits I can prove)
So I understand that fatty acids with 10 or fewer carbons will diffuse straight across the mitochondrial “cell” wall … so short and medium fatty acids are not affected by any inhibition in the carnitine shuttle.
When the shuttle is bottle necked then there are backup organelles called peroxisomes that cleave 12 carbon and larger fatty acids into shorter chained ones … but this process generates heat and hydrogen peroxide. This may be a very old holdover from before our ancestor captured and enslaved the mitochondria. We may have retained it to maintain flexibility in situations when mitochondria went haywire.
We can store some fatty acids in lipid droplets in cells and they may mechanically inhibit the insulin mediated glucose receptor (GLUT4) from getting to the cell wall - so lipid backup in the cell produces insulin resistance … which makes sense from a systemic standpoint.
The other control point that is interesting from a systemic standpoint is … what switches us between using fat and using glucose (and making fat with any we don’t use) is the presence of Malonyl-CoA and it’s mechanism is to inhibit the carnitine shuttle shutting off the spigot of fat entering the mitochondria so it can focus on other sources of energy.
It turns out that this signal shutting off the freeway for long chained fats into our mitochondria is insulin going high. Well … the above paper doesn’t take it to that conclusion, they just say glucagon is the on signal for ketogenesis. The approximate sequence is Insulin goes high, glucagon goes low, via AMPK that unblocks synthesis of Malonyl-CoA - that turns off the carnitine shuttle stopping fats from entering in bulk to be burned. When insulin goes low, glucagon rises, via AMPK blocks the synthesis of malonyl-CoA … and we make ketones instead.
The TL;DR version if when Insulin is high we have to get energy from burning glucose and protein and medium chained fats - and we make long chained fats for storage. When Insulin is low the tollgate raises on the long chain fat freeway and we switch to burning fats at full speed.
This explains the paradox of the insulin resistant person who is lethargic, hungry and apparently has plenty of stored energy. They aren’t able to use fats efficiently with that much insulin in circulation.
This also explains why we make fat in every cell when insulin is high - because our cells are either making ketones or fat (denovo) from fuel in excess to the capacity of our krebs cycle. And if our fat cells are healthy, at a signal from insulin they hoover it all up for storage.
The other thing I believe this explains is why very deranged people lose a lot of weight on keto then stall. In the starting glucose burning state our fat cells have become insulin resistant and unable to hold their fat, spilling it over into circulation. What is actually stopping us using the fat for energy is high insulin is inhibiting the carnitine shuttle in all our cells.
Keto usually lowers insulin sufficient to enable use of fat for energy and we’re off to the races … until out fat cells get rid of enough of their cargo to become insulin sensitive again. If we can lower our insulin below a certain point there is not plateau … we just keep cruising lower till we hit other constraints on fat loss. If we cant lower insulin below the point needed to release the inhibition on our now healthy fat cells … plateau city. And then the goal is to find ways to get insulin below that 13 mIU/l point above which fat cells are inhibited from releasing energy for use.