Podcast 78 - Lactate & The Glycolytic Flux Capacitor


I was listening to Eric give a lecture during his ventilator pre-conference workshop. I forget the exact context, but he mentioned that lactate was a normal product of glycolysis. While lactate can be produced through glycolysis, this statement somewhat shook my understanding of how and why lactate is produced. I approached him later and asked him to explain why you would need to produce lactate if there was neither a supply or demand of oxygen. I asked Sam and Chip Lange from TOTALEM to come on and chat nerdy with me.

At the end of glycolysis you end up with:

Two Pyruvate

Two NAD+

Two ATP

Now the pyruvate will need to donate an electron to NAD+ (which will now be called NADH).

The NADH will now carry that electron into the mitochondria to begin Kreb cycle and eventually the electron transport chain (ETC). There are a few things that can disrupt this process.

Anaerobic Metabolism: In the absence of oxygen, the ETC will begin to back up. The entire reason we NEED oxygen is to operate as the final electron accepter in the production of ATP. Imagine a water brigade that terminates with someone who is unable to empty their bucket, the entire line would then back up. This is exactly what happens when oxygen is not present or demand exceeds supply.

Glycolytic Flux: As catecholamines surge, the rate of glycolysis will increase. The pyruvate will not be able to donate an electron to NADH (because it's already loaded with an electron).

Keep in mind, this is not because there is a lack of oxygen , but rather because the Kreb cycle is moving at a slower rate than glycolysis. When this occurs, pyruvate will be converted to lactate and be able to accept the electron from NADH thus oxidizing it back to NAD+.

The pyruvate will then enter into something called the Cori Cycle.

This can be seen in studies that evaluate beta adrenergic drug therapy in correlation with lactate production. In one study published in CHEST (Lewis, 2014), they discovered a significant correlation between plasma albuterol levels and linear increases in lactate. This probably explains why septic patients who typically present with INCREASED cardiac output, still accumulate lactate.

So thats real cool and all, but is an accumulation of lactate bad?

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References:

Lewis, L. M., Ferguson, I., House, S. L., Aubuchon, K., Schneider, J., Johnson, K., & Matsuda, K. (2014). Albuterol Administration Is Commonly Associated With Increases in Serum Lactate in Patients With Asthma Treated for Acute Exacerbation of Asthma. Chest, 145(1), 53–59.doi:10.1378/chest.13-0930.

Hernández G, Ospina-Tascón GA, Damiani LP, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019;321(7):654–664. doi:10.1001/jama.2019.0071

The "Hiker's" that didn't accumulate lactate when their Pa02 dropped.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa0801581