Lactate and pyruvate: the pathway in the body · Biomarker & Laboratory Analysis

This page shows the biochemical pathway behind the laboratory value Lactate, pyruvate: which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Pyruvate stands at the end of glycolysis; lactate forms from it when hydrogen is transferred from NADH. Both travel between tissues, and the liver builds glucose from lactate again. The ratio of NADH to NAD⁺ steers lactate dehydrogenase.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. Glucose → Pyruvate Glycolysis · NAD⁺, ADP Glycolysis ends with pyruvate. Along the way, the cell gains ATP, and NAD⁺ picks up hydrogen, becoming NADH. Pyruvate is the switch point between lactate and the route into the mitochondria. Source 1↑ supplies Pyruvate is the switch point: in the cytoplasm it becomes lactate, in the mitochondrion acetyl-CoA or oxaloacetate. Where it goes is set by the ratio of NADH to NAD⁺ and the activity of the PDH complex. established physiology Source 1, 2
   ⚖ When the balance tips

   too much — If pyruvate builds up because the PDH complex or the respiratory chain cannot keep up, lactate dehydrogenase transfers more hydrogen to it, and more lactate forms.

   too little — If little pyruvate is available, the citric acid cycle and new glucose formation receive less supply; the cell can also recover pyruvate from lactate.

   established physiology · Source 1, 2

2. Pyruvate → Lactate Lactate dehydrogenase · NADH Lactate dehydrogenase transfers hydrogen from NADH to pyruvate; this forms lactate and frees NAD⁺ again. The reaction runs in both directions. This lets glycolysis keep running. Source 1↑ supplies When lactate forms, NAD⁺ is released, which glycolysis needs to keep running. Lactate is not an end product: other cells convert it back to pyruvate and use it as fuel. established physiology Source 1
   ⚖ When the balance tips

   too much — If lactate builds up in the cell, the MCT transporters move it out together with a proton; if they cannot keep up, lactate and protons accumulate inside the cell.

   too little — If little lactate forms, the cell recovers the NAD⁺ for glycolysis mainly via the mitochondria, whose respiratory chain turns NADH back into NAD⁺.

   established physiology · Source 3, 1

3. Lactate → Lactate in the blood MCT1, MCT4 Transporters of the MCT family move lactate out of the cell together with a proton. Other tissues, such as heart muscle and brain, absorb it again via the same transporters. In the blood, lactate is a fuel that travels between tissues. Source 3, 1↑ supplies Lactate in the blood is a fuel that travels between tissues: working muscles release it, while the heart, brain, liver and resting muscles absorb it. The lactate shuttle theory describes this exchange. established physiology Source 1, 3
   ⚖ When the balance tips

   too much — If release exceeds uptake, for example during intense muscle work, lactate accumulates in the blood; the liver, heart and resting muscles then absorb more of it and convert it.

   too little — If little lactate reaches the blood, the liver has less starting material for new glucose formation, and other tissues rely more on glucose and fats.

   established physiology · Source 1, 4

4. Lactate in the blood → Glucose in the liver Gluconeogenesis · ATP The liver rebuilds glucose from lactate and releases it into the blood. This loop of release and new formation is called the Cori cycle. It uses ATP to do so. Source 4, 1↑ supplies New glucose formation from lactate returns glucose to the blood, especially during fasting. It uses ATP, which the liver gains mainly from breaking down fatty acids. established physiology Source 4, 1
   ⚖ When the balance tips

   too much — If new glucose formation runs strongly, for example under glucagon during fasting, the liver uses more lactate and ATP and releases more glucose into the blood; insulin slows this pathway.

   too little — If new glucose formation runs slowly, the liver absorbs less lactate, and the glucose in the blood comes more from the liver's glycogen store.

   established physiology · Source 4

5. Pyruvate in mitochondria → Acetyl-CoA PDH complex · Thiamine (B1), Lipoic acid The pyruvate dehydrogenase complex removes carbon dioxide and attaches the remainder to coenzyme A. It works with five helpers: thiamine, lipoic acid, FAD, NAD and coenzyme A. If acetyl-CoA builds up, it slows the complex itself. Source 2↑ supplies Acetyl-CoA brings the carbon from pyruvate into the citric acid cycle. The PDH complex needs B1 (thiamine), B2 (FAD), B3 (NAD⁺), B5 (in coenzyme A) and lipoic acid for this; if one is missing, the step slows. established physiology Source 2
   ⚖ When the balance tips

   too much — If acetyl-CoA builds up together with NADH, both slow the PDH complex and activate its kinases; less pyruvate is converted, and more of it goes to pyruvate carboxylase.

   too little — If little thiamine or lipoic acid is available, the PDH complex cannot keep up; pyruvate builds up, and lactate dehydrogenase makes more lactate from it.

   established physiology · Source 2, 5, 1

6. Pyruvate in mitochondria → Oxaloacetate Pyruvate carboxylase · Biotin, ATP Pyruvate carboxylase adds carbon dioxide to pyruvate. In the liver, this substance is also the starting point of new glucose formation. With little biotin, the carboxylase works more slowly. Source 4↑ supplies Oxaloacetate replenishes the citric acid cycle when intermediates are drawn off, and in the liver it is the entry point to new glucose formation. Pyruvate carboxylase needs biotin, ATP and bicarbonate for this. established physiology Source 5, 4
   ⚖ When the balance tips

   too much — If plenty of oxaloacetate is available, more acetyl-CoA can enter the cycle; in the liver the excess flows into new glucose formation.

   too little — If little biotin is available, pyruvate carboxylase works more slowly; the cycle then has less oxaloacetate as a partner for acetyl-CoA, and pyruvate builds up before this step.

   established physiology · Source 5, 4

7. Acetyl-CoA → Citric acid cycle Citrate synthase Acetyl-CoA and oxaloacetate together form citrate. In the cycle, the carbon is broken down step by step to carbon dioxide; NAD⁺ and FAD pick up hydrogen along the way. The loaded carriers bring the electrons to the respiratory chain. Source 2, 4↑ supplies The cycle strips electrons from acetyl-CoA and uses them to load NAD⁺ to NADH and FAD to FADH₂; these carriers deliver them to the respiratory chain. Its intermediates also serve as building blocks. established physiology Source 2, 4
   ⚖ When the balance tips

   too much — If NADH builds up because the respiratory chain does not convert it back quickly enough, it slows the PDH complex and the cycle; more pyruvate then passes into lactate.

   too little — If the cycle receives little acetyl-CoA or oxaloacetate, it passes fewer electrons to the respiratory chain, and the cell forms less ATP there.

   established physiology · Source 2, 1, 5

8. Oxaloacetate → Citric acid cycle Citrate synthase Acetyl-CoA and oxaloacetate together form citrate. In the cycle, the carbon is broken down step by step to carbon dioxide; NAD⁺ and FAD pick up hydrogen along the way. The loaded carriers bring the electrons to the respiratory chain. Source 2, 4↑ supplies The cycle strips electrons from acetyl-CoA and uses them to load NAD⁺ to NADH and FAD to FADH₂; these carriers deliver them to the respiratory chain. Its intermediates also serve as building blocks. established physiology Source 2, 4
   ⚖ When the balance tips

   too much — If NADH builds up because the respiratory chain does not convert it back quickly enough, it slows the PDH complex and the cycle; more pyruvate then passes into lactate.

   too little — If the cycle receives little acetyl-CoA or oxaloacetate, it passes fewer electrons to the respiratory chain, and the cell forms less ATP there.

   established physiology · Source 2, 1, 5

9. Citric acid cycle → Respiratory chain · NADH, FADH₂ NADH and FADH₂ pass their electrons to the respiratory chain. At the end, oxygen accepts them; the cell uses the energy of this route to form ATP. This frees NAD⁺ and FAD again for the cycle. Source 2↑ supplies The respiratory chain accepts the electrons from NADH and FADH₂, returns NAD⁺ and FAD to the cycle and uses the electron flow to form ATP. Coenzyme Q10 carries the electrons from complex I and II to complex III. established physiology Source 6, 2
   ⚖ When the balance tips

   too much — If more electrons enter the chain than drain away at the end, the flow backs up; at complex I and III more single electrons then escape and form reactive oxygen species.

   too little — If little oxygen arrives or little coenzyme Q10 is available, NADH builds up; the cell then recovers more NAD⁺ via lactate dehydrogenase, and more lactate forms.

   established physiology · Source 6, 1

Further stations

• Glucose — dextrose Glucose passes from the blood into the cell. In the cytoplasm, glycolysis begins: a chain of ten reactions that runs without oxygen. Its breakdown supplies ATP and NADH. Source 1↑ supplies Glucose is the starting material of glycolysis: its breakdown to pyruvate supplies ATP and loads NAD⁺ to NADH, even without oxygen. established physiology Source 1
  ⚖ When the balance tips

  too much — If a lot of glucose enters the cell, more pyruvate forms than the mitochondria absorb; part of it passes via lactate dehydrogenase into lactate, even with enough oxygen.

  too little — If little glucose arrives, less pyruvate forms; tissues such as the heart and brain can then use lactate from the blood as fuel.

  established physiology · Source 1

• Pyruvate in mitochondria — via the MPC carrier The MPC carrier moves pyruvate across the inner mitochondrial membrane. Two routes are open there: breakdown to acetyl-CoA and replenishing the citric acid cycle. Acetyl-CoA steers which route predominates. Source 2↑ supplies In the mitochondrion it is decided whether pyruvate is broken down via the PDH complex or replenishes the citric acid cycle via pyruvate carboxylase. Acetyl-CoA steers: it slows the PDH complex and activates the carboxylase. established physiology Source 2, 5
  ⚖ When the balance tips

  too much — If a lot of pyruvate enters the mitochondrion, it inhibits the kinases that switch off the PDH complex; the complex stays active and converts more of it to acetyl-CoA.

  too little — If little pyruvate enters the mitochondrion, more of it stays in the cytoplasm; lactate dehydrogenase then converts more of it to lactate.

  established physiology · Source 2, 1

Cofactors in this pathway

• NAD⁺ — Accepts hydrogen during glycolysis; lactate dehydrogenase releases it again; so glycolysis keeps running Source 1, 2In the ORY catalogue as a laboratory value: NAD⁺ (Nicotinamidadenindinukleotid)
• Thiamine (vitamin B1) — As thiamine diphosphate, cofactor within the pyruvate dehydrogenase complex; with little of it, pyruvate backs up Source 2
• Lipoic acid — Carries the acetyl group from one subunit to the next in the PDH complex; without it the complex stalls Source 2
• Coenzyme A — Accepts the acetyl group, forming acetyl-CoA for the citric acid cycle Source 2
• FAD (vitamin B2) — Cofactor of dihydrolipoyl dehydrogenase within the PDH complex, which reoxidises the lipoic acid Source 2
• Biotin — Cofactor of pyruvate carboxylase, which converts pyruvate into oxaloacetate; this replenishes the cycle Source 5
• Magnesium — Pyruvate carboxylase works with MgATP and bicarbonate; the ATP supplies the energy Source 5In the ORY catalogue as a laboratory value: Magnesium
• Coenzyme Q10 — Carries the electrons from complex I and II onwards in the respiratory chain; with little of it, NADH backs up Source 6In the ORY catalogue as a laboratory value: CoQ10 (Coenzym Q10)

Sources

1. Brooks GA. The Science and Translation of Lactate Shuttle Theory. Cell Metab 2018 · PubMed 29617642
2. Patel MS, Nemeria NS, Furey W et al. The pyruvate dehydrogenase complexes: structure-based function and regulation. J Biol Chem 2014 · PubMed 24798336
3. Halestrap AP. The monocarboxylate transporter family—Structure and functional characterization. IUBMB Life 2012 · PubMed 22131303
4. Rui L. Energy metabolism in the liver. Compr Physiol 2014 · PubMed 24692138
5. Jitrapakdee S, St Maurice M, Rayment I et al. Structure, mechanism and regulation of pyruvate carboxylase. Biochem J 2008 · PubMed 18613815
6. Wang Y, Lilienfeldt N, Hekimi S. Understanding coenzyme Q. Physiol Rev 2024 · PubMed 38722242

Related pathways

• Liver enzymes — lactate
• Biotin — oxaloacetate
• Citric acid cycle — oxaloacetate
• NAD⁺ — respiratory chain
• Alanine — NAD⁺ (Nicotinamidadenindinukleotid), Magnesium

As of 2026-09-16. Draft, written by Claude to schema v2; sources checked in PubMed; expert approval pending
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