Lactate: the ugly duckling of energy metabolism, 2020, Rabinowitz and Enerbäck

Lactate: the ugly duckling of energy metabolism
Rabinowitz JD, Enerbäck S

Lactate, perhaps the best-known metabolic waste product, was first isolated from sour milk, in which it is produced by lactobacilli. Whereas microbes also generate other fermentation products, such as ethanol or acetone, lactate dominates in mammals.

Lactate production increases when the demand for ATP and oxygen exceeds supply, as occurs during intense exercise and ischaemia. The build-up of lactate in stressed muscle and ischaemic tissues has established lactate's reputation as a deleterious waste product.

In this Perspective, we summarize emerging evidence that, in mammals, lactate also serves as a major circulating carbohydrate fuel. By providing mammalian cells with both a convenient source and sink for three-carbon compounds, circulating lactate enables the uncoupling of carbohydrate-driven mitochondrial energy generation from glycolysis. Lactate and pyruvate together serve as a circulating redox buffer that equilibrates the NADH/NAD ratio across cells and tissues.

This reconceptualization of lactate as a fuel-analogous to how Hans Christian Andersen's ugly duckling is actually a beautiful swan-has the potential to reshape the field of energy metabolism.

PubMed Link | PubMed PDF | Nature Metabolism PDF

 

I've read it through and while it would probably take another couple of runs to better follow the detail, the overview seems potentially quite relevant. (It fortuitously came up on my Twitter feed via Nature Metabolism's "throwback Thursday".) A few high-level quotes that caught my eye —

Also, having reported PET scans for over 10 years, I enjoyed stopping for a moment to think about something that is fundamental to the technique, but which we don't tend to think about the underlying nature of —

 

The more they work out how energy is produced the closer they will be to finding the cause of ME. Vice versa, studying ME may give them insight into energy production by looking at our symptoms.

I get a deep, acid burning in my muscles if they are overused. Some process has gone wrong.

 

Agreed.

The article says lactate production increases when demand for ATP and oxygen are in short supply. My legs become very painful, when climbing stairs and small hills. So not after a run, just a bit of normal walking. In PEM, my legs can be very painful just walking on the main floor of my house.

If science understands at least some of the mechanism of lactate versus ATP and oxygen, it would very good if there could be more study focused on how this goes wrong in ME.

I'm also wondering if this is somehow tied up with RBCs, and blood circulation studies in ME.

When I was quite anemic, the fatigue, palpitations, shortness of breath, and leg pain became even more pronounced. I had more frequent crashes, and spent even more time couch ridden. At one point I couldn't walk across one room without needing to rest due to leg pain and shortness of breath.

My hemoglobin had been tested, and was good, which supposedly ruled out iron deficiency. However, a later test revealed ferritin in the iron deficiency range.

We get these brief glimmers of insight into ME. It would be wonderful if researchers could piece it all together.