Summary
Chris Masterjohn discusses emerging research on D-lactate, a less-studied form of lactate with important implications for gut health and metabolic function. He explains how D-lactate differs from L-lactate and why this research matters for understanding digestive disorders.
Key Points
- D-lactate is produced by certain gut bacteria and differs from exercise-produced L-lactate
- Excess D-lactate can cause neurological symptoms and metabolic issues
- Certain gut conditions may increase D-lactate production
- Dietary factors influence D-lactate-producing bacterial populations
- Testing for D-lactate may help explain unexplained neurological symptoms
Key Moments
So it's not just negative feedback against its own production
So it's not just negative feedback against its own production. It's also negative feedback against the rising NADH to NAD plus ratio under the circumstances where that ratio rises enough to start...
"The rising NADH to NAD plus ratio can't just inhibit glycolysis and say, who cares, it's just glycolysis. It's also inhibiting every other NAD plus dependent reaction in the cytosol, which there are many. So you always want to be able to regulate that ratio to keep it where it's supposed to be. And it just so happens that it's supposed to be very oxidized, meaning very NAD plus dominant, not NADH dominant, which is what allows glycolysis to go forward at a very rapid rate."
Now, glycolytic methylglyoxal acts as negative feedback on the step that increases cytosolic NAD plus demand
Now, glycolytic methylglyoxal acts as negative feedback on the step that increases cytosolic NAD plus demand.
"you're hydrolyzing NAD+, and you have not adequately restored the NAD levels with niacin, so it could be a niacin deficiency or just an absolute deficiency of NAD+, in general, or a high NADH to NAD+, ratio, methylglyoxal is helping with all of these things. But as we'll see later with more emphasis and elaboration, methylglyoxal is the only way to get pyruvate out"
So let's say that despite all this, you still have a backup of NAD plus and the cytosol
are not sufficient. So let's say that despite all this, you still have a backup of NAD plus and the cytosol.
"And you have a traffic jam. You're trying to funnel NADH into a place where it can't escape. That's going to worsen the NADH to NAD plus ratio in the cytosol. So plan A is you use the malate aspartate shuttle because that's where you get the most ATP. Plan B is you use the glycerol phosphate shuttle because that can take care of a declining NADH, declining NAD plus in the cytosol if complex one is backed up. Plan C is you use the delactate shuttle"
