You've cited one study. Can it be reliably repeated?The first line of this article explains that the Mitochondrial Dicarboxylate Carrier operates on the inner mitochondrial membrane.
Succinate cannot reach this transporter if it is not cell-permeable.
The paper I cited previously shows that succinate is not cell-permeable with experimental evidence: https://www.nature.com/articles/ncomms12317
As Hip explained, it's possible that succinate has other actions throughout the body due to the widespread presence of succinic acid receptors. I don't think it's fruitful to continue discussions about succinic acid entering cells in significant quantities when all literature indicates otherwise.
Here's a contrasting study:
SLC-13 appears to be the transporter:
As succinate can be released into the extracellular space from the cytoplasm, succinate may also enter into the cytosol. We then determined levels of intracellular and extracellular succinate after treating hPDLCs with succinate. Succinate concentration in the cytosol climbed in an early phase of succinate stimulation, peaked at 6 h, and then declined later on (Figure 4(a)). In contrast, succinate concentration in the extracellular space decreased over time in succinate-treated cells (Figure 4(b)). In line with elevated succinate in the cytosol, the protein level of HIF-1α was increased, whereas the level of PHD was reduced (Figure 4(c)). Then, changes in glycolysis-related genes were analyzed. Both HK2 and PFKFB3 were elevated with the succinate supplement (Figures 4(d) and 4(e)). Furthermore, it was observed that SDH transcription elevated at 4 h while the SDH protein level diminished in succinate-supplemented hPDLCs (Figures 4(d) and 4(e)). Additionally, reduced SDH enzyme activity was found in 5 mM succinate-treated cells (Figure 4(f)). Therefore, our present data suggest that exogenous succinate can be transferred into the cytosol, where it induced PHD suppression, leading to a pseudohypoxia condition and HIF-1α stabilization. Therefore, such HIF-1α pathway activation was crucial in succinate supplement-induced stem cell proliferation.
We've seen exogenous succinate reliably resolve hypoxia numerous times and presented as additional supporting evidence, has been successfully used to "rescue" 2 people who performed the GDH-knockdown fast and then (ignoring advice) consumed food during the GDH-knockdown period, leading to the state described in the third paper.
One other person who also ignored the advice on not eating was unable to reach his succinate due to repeatedly blacking out every few seconds due to loss of mitochondrial energy... for hours... until the EGCG wore off. This is why I put the large disclaimers in the third paper - if someone chose to ignore this advice and eg. drive a car in this state, while eating food, I could see this easily being fatal.
I have no doubts that further lab experiments will explain any gaps in the limited published literature on this.
I was talking subjectively and really this observation was based around PEM load.50g of glucose contains 200 calories.
50mg of succinic acid is certainly not equivalent to 200 calories, and my 500mg dose was not equivalent to 2000 calories.
This is a physically impossible claim. No substance can be that calorie-dense.
50mg of succinic acid can induce roughly the same amount of PEM as about 50g of glucose. The a-KGDH bypass effect is likely a confounding factor in this observation and overall, it needs to be properly studied. The anaplerosis would also likely skew the lactateyruvate ratio, in the same way the glutaminolysis does.
As a dietary input, I don't believe anyone has quantified the calorific density of these organic acids in the literature. I haven't looked into the specifics yet either, this is only by general indications / observations.
I suppose it'll need to be done at some stage, so I guess I'll give it a brief spit-ball now.. Now this is currently straying slightly outside of my normal comfort zone, however I'll go out on a limb briefly, at least until I've better studied, digested and understood this. Maybe some input from others will help:
At the basic level, we're talking about chemical reactions that involve electrons, electron chain transport, hydrogen and the formation of ATP.. Great.. so let's look into the thermochemistry..
What's the energy density of hydrogen?
...It's probably the most energy dense thing I'm aware of, at >120-140kJ per g.
Succinic acid is C4H6O4
By weight, succinic acid is very close to 5% hydrogen, 40% carbon and 55% oxygen.
So at this point, seems like a suitably energy dense compound.
So, as a direct calorific measurement, from these musings, it appears to be less than glucose. Measured this way, it's roughly 3 Kcal/gram, however this really doesn't describe the relationship to avoiding all of the processes involved in glucose metabolism, glycolysis and fatty acid oxidation before it reaches the citric acid cycle.
Chemically, succinic acid sits directly before/after the "primary" reversible reaction which generates ATP:
There is one reversible reaction to/from succinyl-coa:
Overall, I believe there is a significantly underappreciated value to succinic acid, which I'll be detailing further in future papers.