I’ve been wondering for a while and can’t seem to find info on how lactate is re-introduced to an ATP producing system. Lots of articles state that the body would rather use lactate than glucose, but lactate is broken down glucose with 2 electrons attached, so it would seem to carry less energy. With that in mind, does it enter glycolysis again at a different stage? or does it enter the Krebb cycle? Anyone know?
Basically I’m in 200 level biology and just wondering how this fits in with what I’ve learned so far. Thanks in advance!
Thanks for the links guys, but neither fully answers my question.
KEAU: The picture shows how lactate is produced, not how it is used as fuel (produces ATP).
Pantelones: The article says “75-80% of lactate is used to produce energy through oxidation, with the remainder converted to glucose and glycogen”. Anyone know the oxidation process (and not just that it loses electrons… what’s the enzyme, intermediates, products, etc…)? I think the Cori Cycle accounts for the glycogen and glucose production, but still unsure where the 75-80% ends up.
The schematic posted by Francois shows how lactate can be rebuild through anaplerosis into glucose and/or glycogen. However, lactate as an acute substrate for ATP generation will -after being converted to pyruvate via Lactate Dehydrogenase (LDH)- enter the TCA/Krebs cycle, as you suggested.
Winner! Except since NAD+ is reduced to NADH during Lactate Dehydrogenase, don’t you just end up where you started fermentation: 1 NADH and 1 Pyruvate (well, 2 per glucose molecule)? Or is Lactate a temporary storage unit for the energy in pyruvate until enough oxygen becomes available to start accepting electrons from NADH and creating demand with NAD+?
That’s cool, but the original question was what’s the pathway/mechanism of breakdown? Are you suggesting another pathway than lactate dehydrogenase → Krebb’s cycle?
That’s it-- Lactate/Lactic acid is produced from an incomplete breakdown of glucose. 1 glucose = 2 lactate molecules via glycolysis that occurs in the cytosol. These are 3 carbon molecules (incomplete breakdown) versus an end product of pyruvic acid/pyruvate (3 carbons also) that can continue to be broken down to CO2 in the mitochondria of the cell (aerobic metabolism).
As far as i know I don’t recall lactate being using in the Krebs Cycle. It would have to enter somehow into the mitochondria. I do know for sure that lactate CAN be reconverted to glucose in the liver via the Cori cycle. http://en.wikipedia.org/wiki/Cori_cycle
The real benefit of lactate production, as mentioned by a previous poster is that you can reconvert NAD to NADH which can be used to continue the last portion of glycolysis. That is until H+ ions build up and stop exercise. Essentially lactate production allows us to exercise intensely for an increased period of time.
Yea, that’s glycolysis without all of the structures. Kind of scary. And I misspoke in my earlier post. When pyruvate is converted to lactate, NADH is reconverted back to NAD to be used back up in step 6.
That’s exactly what the biochem prof said to me in class! (before going to maths and computer science I did a bs in biology…the 4 x 8hrs if biochem last only to extract beta galactosidase from e-coli was enough to deter me from going any further in bio research!)
Fermentation creates NAD and Lactate which keeps glycolysis running. Less pyruvate is available to the Krebs Cycle and therefore oxidative phosphorylation slows and glycolysis rises. The glycolysis creates ATP and builds up a “store” of lactate. When there is enough oxygen to start taking up NADH through oxidative phosphorylation, the Kreb cycle kicks into gear again and the stored lactate is converted to pyruvate and NADH which is why it’s accepted in the krebs cycle more readily than glucose. Do I have this straight?
Caveat: I’m not insinuating that these things happen in isolation (example: the Krebs cycle and oxidative phosphorylation stop when there’s a deficit of oxygen). It’s just easier to describe and think about by pretending they do. All these parts are running all the time, but at varying rates.
Indeed, to get lactate to enter the TCA cycle, it needs first converted back to pyruvate, from which it originates. An explanation would be that the potential energy of pyruvate oxidation is stored as lactate, as you mentioned. However, keeping NAD available seems a much more important feature of extending glycolysis to lactate instead of ending at pyruvate.
Although there’s still quite some debate going on, the most common explanation of how lactate acts as a muscle fuel involves compartmentation: lactate produced in type II (fast twitch) muscle fibers is transported out of this fiber into a (neighbouring) type I (slow twitch) fiber. The slow twitch fiber at his turn oxidizes lactate via the TCA cycle. This intercellular shuttle mechanism requires lactate transporters that are specific for export and import of lactate. These are the monocarboxylic acid transporters (MCT’s). Furthermore, there are indications that different isoforms of LDH exist in these different compartments, with higher affinity to convert pyruvate to lactate (in fast twitch) or lactate to pyruvate (in slow twitch fibers). Even an intra-cellular version of this shuttle has been suggested to explain how lactate is produced in the cytosol and aerobically metabolized in mitochondria of the same cell (search “Brooks GA” for literature). Other examples in biology of very similar compartmentalized lactate metabolism are the brain: astroglia cells producing and neurons oxidizing lactate; and even some tumors have been suggested to produce lactate in their necrotic, oxygen deprived core and oxidize it in their vascularized outer layers of tumor tissue.
Fermentation creates NAD and Lactate which keeps glycolysis running. Less pyruvate is available to the Krebs Cycle and therefore oxidative phosphorylation slows and glycolysis rises. The glycolysis creates ATP and builds up a “store” of lactate. When there is enough oxygen to start taking up NADH through oxidative phosphorylation, the Kreb cycle kicks into gear again and the stored lactate is converted to pyruvate and NADH which is why it’s accepted in the krebs cycle more readily than glucose. Do I have this straight?
Caveat: I’m not insinuating that these things happen in isolation (example: the Krebs cycle and oxidative phosphorylation stop when there’s a deficit of oxygen). It’s just easier to describe and think about by pretending they do. All these parts are running all the time, but at varying rates.
Thanks for the help everyone!
except it’s not really dependent on oxygen availability. there is always oxygen available.
