NAD+ regeneration by lactate dehydrogenase in anaerobic glycolysis
Lactate dehydrogenase, the enzyme that turns pyruvate into lactate, converts NADH back into NAD+ (an electron carrier), so step 6 of glycolysis can keep running when oxygen is limited.
Remember
When oxygen is limited, step 6 of glycolysis keeps going because lactate dehydrogenase passes the electrons from NADH to pyruvate, giving lactate and NAD+. That reaction makes no ATP itself.
Memory aid
NAD+ is an empty electron taxi and NADH is a full one; step 6 needs an empty taxi, and lactate dehydrogenase is the depot that empties it.
Use it to recall that step 6 needs NAD+ and that lactate dehydrogenase restocks it by emptying the NADH.
Step 6 of glycolysis makes 2 NADH per glucose, so it needs a steady supply of NAD+. The cell holds only a limited amount of it, so each NADH has to be turned back into NAD+. In most cells the electron transport chain (the oxygen-using relay of proteins in the mitochondria) does this job, but it needs oxygen.
In a sprint, or when blood flow to the tissues is poor, oxygen delivery falls short. NADH then builds up and NAD+ runs out, so without a fresh supply of NAD+ step 6 would slow or stop. The way out is lactate dehydrogenase, which adds the electrons from NADH to pyruvate (the end product of glycolysis). This forms lactate and regenerates NAD+ in the cytosol (the fluid part of the cell outside the organelles), without needing oxygen.
Notice what lactate formation does not do: it makes no ATP itself. Its job is to keep step 6 supplied with NAD+, so that the later ATP-making steps can carry on. The lactate is then carried to the liver, where it is broken down back into pyruvate.
Some cells have no mitochondria, such as red blood cells, so they depend on this route all the time. If lactate builds up too far, with blood lactate above 5 mmol/L, the blood becomes acidic. This is called lactic acidosis, and in pathological situations, such as heart failure, it is a marker of severe illness.
Key facts
- Why NAD+ matters
- step 6 needs NAD+ and makes NADH, with 2 NADH per glucose.
- Usual route
- in most cells the electron transport chain turns NADH back into NAD+, but it needs oxygen.
- Without oxygen
- pyruvate plus NADH becomes lactate plus NAD+, which lets glycolysis continue.
- ATP
- lactate formation itself makes none; it keeps the pathway running.
- Fate of lactate
- it passes into the blood and is carried to the liver.
- Lactic acidosis
- a blood lactate above 5 mM lowers the blood pH, and in pathological situations, such as heart failure, this is a marker of severe illness.
Exam traps
- Increased electron transport chain activity does not solve the problem in a maximal sprint, because the chain passes electrons on to oxygen and so is restricted when oxygen delivery is the limiting factor.
- Converting lactate back to pyruvate does not relieve the shortage at step 6, because it runs in the opposite direction: it uses up NAD+ and makes NADH.
- The malate-aspartate shuttle does not keep NAD+ available when oxygen is limited, because it carries electrons from cytosolic NADH into mitochondria, where they still have to be passed along the oxygen-dependent chain.
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