The Whole Lactate Story

RBR asked some rather deep questions about lactate metabolism and since I've never seen it described well anywhere, I'll try to give a complete account. How I could I say no to this face?


When muscle cells are low on oxygen, they convert pyruvate into lactate using an enzyme called lactate dehydrogenase. This is a dead end, so the cells hold lactate until there's more oxygen and then use the same enzyme to reconvert it. If the lack of oxygen is long enough, lactate builds up to the point where stoichiometry forces the lactate back to pyruvate; this is a major problem, which is ameliorated by having the lactate leak out of the cells into the bloodstream.


Blood carrrying lactate goes to the liver, which also has the same lactate dehydrogenase as muscles, but which always has oxygen, so the burden of reconversion of lactate to pyruvate gets partly done away from the muscles.


Before the blood gets to the liver, however, it goes through the heart, which has a different isozyme of lactate dehydrogenase. This enzyme has a much higher affinity for lactate than pyruvate, so it converts lactate to pyruvate readily. This is due to the fact that heart muscle prefers using pyruvate to glucose as an energy source, probably due to the fact that the blood in the heart muscle is always highly oxygenated. This isozyme, however, is allosterically inhibited by pyruvate; once the heart has the energy it needs, it stops the conversion and the remaining lactate goes to the liver.



If the lack of oxygen in muscle continues long enough, it gets produced faster than it can be excreted and the lactate gets forced back to pyruvate, which would build to toxic levels, if there were not another method to get rid of it. The excess pyruvate gets transaminated to alanine (with concomitant conversion of glutamate to alpha-ketoglutarate), which gets excreted into the blood and reconverted by the liver, much the same way as lactate; alanine tends to be much less toxic than pyruvate or lactate. This process requires free glutamate, which is not in large supply in muscle cells, so it gets replenished by the alpha-ketoglutarate generated being transaminated by glutamine. If the cell's free glutamine gets used up, there is a method to replenish it by protein degradation and/or glutamine synthetase, a process that would need its own post to describe fully. After an event like a marathon race, blood lactate levels will be elevated for hours and glutamine levels may be low for days; for this reason, many products designed for athletes recovering from exercise will have added glutamine, though an adequate diet works as well to replenish these stores.
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So, to answer your questions, RBR, almost all cells contain lactate dehydrogenase, but few of them generate much lactate except striated muscle cells. Lactate metabolism is of minor import to tissues other than skeletal muscle, cardiac muscle and hepatocytes; they can use lactate if it's there.