Hydrogen economy in glycolysis:
Out (–)
In (+)
HK
H⁺
PFK
H⁺
2GAPDH
2NAD
H 2H⁺
2ENO
2H₂O
2PK
2H⁺
Total
10H
2H
The expectation (–10H + 2H = –8H) is different from the actual change (–6H), when we obtain the pyruvates:
Toxin
Formula
Glucose
C6
H12O6
(
–8H →) Expected
C6
H4O6
(
–6H →) 2Pyruvate
C6
H6O6
2Lactate
C6
H10O6
2Lactic acid
C6
H12O6
What explains the difference (between expected and actual change) is that the 2H⁺ released at the dehydrogenase level (GAPDH) are derived from inorganic phosphate rather than extracted from the glucose metabolite (NADH + H⁺). When we disconsider these 2H⁺, we arrive on the –6H needed.
As for lactate, when it's formed, 4H are consumed from 2NADH + 2H⁺. Going backwards, it would be equivalent to never having produced:
H⁺ (HK)
H⁺ (PFK)
2NADH (2GAPDH)
Then, we're left with –2H for 2 lactates (C6H10O6) to match with a glucose molecule (C6H12O6).
Even though 2H⁺ were disconsidered previously, they still occur, just not extracted from glucose metabolites. After canceling out the 3 products listed above, we get:
Out (–)
In (+)
2GAPDH
2H⁺
2ENO
2H₂O
2PK
2H⁺
Total
6H
2H
When lactate is exported from the cell, it tends to bring a H⁺ along as counter-ion. So, 2 lactates would take out the equivalent to those 2H⁺ produced at 2GAPDH.
What remains is the bottom of the original table:
2H₂O out (produced)
2H⁺ in (consumed)
Therefore, lactate synthesis and export is an alkalinizing process for the cell:
H⁺ are consumed when pyruvates are formed (pyruvate enol-phosphate + H⁺ → pyruvate), to then become lactates to be exported. In contrast, the H₂O molecules produced are neutral.
LDH reaction consumes H⁺ directly (pyruvate + NADH + H⁺ → lactate + NAD⁺)
Additional H⁺ tend to be eliminated with lactates as counter-ions (lactate + H⁺)
Nevertheless, lactate is associated with acidification for a few reasons that I'm aware of:
The coexport with a H⁺ alkalinizes the interior and acidifies the exterior of the cell. It's easier to monitor the outside, so that's what we associate with.
Once this lactic acid equivalent leaves the cell, the H⁺ is quickly buffered, leaving lactate to pair with available cations, such as Na⁺ ('HLac' + NaHCO3 → NaLac + H2CO3). If not by using up hydrocarbonate ions, a surge of lactate with expansion of the pool of organic anions can lead to an increase in cations to maintain ion neutrality. This tends to reflect on the concentration of free H⁺, that may rise in proportion along.
Marked ATP hydrolysis, that often coincides with excess lactate formation, is acidifying.
ATP + H₂O → ADP + Pi + H⁺
Rather than the theoretical source from the previous section, this H⁺ can be the pair for lactate.
The following diagram has these events simplified:
Metabolic acidosis and fatigue: Where to from here?
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