Science is a self-correcting in its very essence, which is why incorrect and imprecise explanations usually do not stick around for very long before being replaced by ideas better reflecting the true state of nature. At times, however, an inaccurate or simply wrong assumption manages to dodge correction for decades, eventually becoming an accepted way of explaining a phenomenon. If it has been printed in textbooks for aeons, it must be precise enough, so why bother changing it?
The longer a half-truth is let to wander free around books, articles, and lecture halls, the harder it is to get rid of when its validity is questioned. And even when its inaccuracy is admitted, it often is still taught incorrectly by convention. Sometimes this is justified, e.g. when the target audience is not expected to master the topic well, and a simplified version is adequate for describing a principle. However, I’m sure everyone agrees on the importance of accurate language when teaching and publishing for audience well capable of understanding the precise model – if not practiced, it leads to misunderstandings even among academics in their own field.
To bring up an example in exercise biochemistry, let’s look at something that has left many sport science students scratching their heads: the role of lactic acid in metabolic acidosis. It appears to be a very well established construct that you can find in most exercise physiology textbooks. I looked it up in McArdle’s Essentials of Exercise Physiology (3rd ed., 2006), and this is their version:
“Hydrogen ions (H+) dissociating from lactic acid, rather than undissociated lactate (La–), present the primary problem to the body. At normal pH levels, lactic acid almost completely dissociates immediately to H+ and La– (C3H3O3–).”
Is this an accurate description of what happens in a vigorously contracting muscle fibre? Contrary to the widespread public opinion, no. Looking up the reactions in any biochemistry textbook shows us that no biochemical reaction is directly producing lactic acid in the muscle. Instead, lactate is reduced from another basic molecule, pyruvate. The reaction actually consumes those acidity causing hydrogen ions (H+) instead of releasing them.
So where does the excess H+ come from that causes drop in pH? It is, after all, a fact that intense exercise causes both lactate and proton accumulation, leading to pH 6.5 or lower in the contracting muscle. Lactate and H+ is also co-transported out of the fibres as lactic acid, so it is not incorrect to state that lactic acid is the source of the proton load in the blood. In muscle, the direct source of accumulating H+ is, in fact, ATP hydrolysis. Every time an ATP molecule is hydrolysed to ADP and inorganic phosphate, Pi, a proton is released. When the mitochondrial uptake of H+ through the ATP synthase is maxed out, protons are released faster than oxidative phosphorylation can consume them.
In 2004, Robert Robergs and colleagues published an article with the title Biochemistry of exercise-induced metabolic acidosis, criticising the concept of lactic acidosis. They argued that as the overload of protons is not caused by lactate production per se, it should not be termed lactic acidosis, and that the concept of “lactic acid dissociation” should be buried and forgotten. This paper sparked a rather lively dialogue in a series of letters published in the American Journal of Physiology, in which other researchers (Böning et al.) criticised Robergs et al. about leaving out the calculations for total proton balance all the way from glucose or glycogen to lactate and hydrolysed ATP.
Böning had a fair point – in glycolysis (the pathway from glucose to pyruvate), 1 glucose produces 2 H+ together with 2 pyruvate and 2 ATP. When pyruvate is then reduced to lactate, these protons are bound. And when those 2 ATP are finally hydrolysed, 2 H+ are released again. Therefore, summarising these reactions, we do end up with lactate and H+ in a ratio of 1:1.*
Does anaerobic glycolysis generate lactic acid? As there is no argument about the actual reactions taking place, the answer comes down to interpretation and semantics. Robergs et al. would say no, while Böning et al. a definite yes. Lactate and hydrogen ions are generated in equal amounts from separate reactions. To support high rates of glycolysis, the LDH reaction is needed to regenerate NAD+, which is why H+ rises simultaneously with lactate – there’s not one without the other.
So let’s say we approve of the term lactic acid; what is harder to accept is the claim about its dissociation, when explaining the drop in pH. It clearly does not reflect the rather complex series of events leading to the metabolic acidosis we see. Would it hurt to use more accurate language, especially when teaching exercise physiology and biochemistry students, let alone when publishing scientific articles? From my own experience I can say that looking at the LDH reaction has caused me serious headaches during my study years, when trying to makes sense of the mysterious protons that should appear but actually disappear!
*For those interested, here are the reaction equations referred to:
glucose + 2 ADP + 2 Pi + 2 NAD+ → 2 pyruvate + 2 ATP + 2 NADH + 2 H2O + 2 H+ (glycolysis)
2 pyruvate + 2 ATP + 2 NADH + 2 H+ → 2 lactate + 2 ATP + 2 NAD+ (LDH reaction)
2 ATP → 2 ADP + 2 Pi + 2 H+ (ATP hydrolysis)
Summary reaction with terms cancelled out:
glucose → 2 lactate + 2 H+
Further reading:
Robergs, R.; Ghiasvand. F; Parker, D. Biochemistry of exercise-induced metabolic acidosis. Am J Physiol Regul Integr Comp Physiol. 2004 Sep;287(3):R502-16.
Böning, D.; Strobel, G.; Beneke, R.; Maassen, N. Lactic acid still remains the real cause of exercise-induced metabolic acidosis. Am J Physiol Regul Integr Comp Physiol. 2005 Sep;289(3):R902-3; author reply R904-910.
Hilkka Kontro is a Research Assistant in Physiology here at the University of Limerick. View Hilkka’s profile here!
Hilkka’s Email: hilkka.kontro@ul.ie
Hilkka’s Twitter: @HilkkaKontro
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