Original episode & show notes | Raw transcript
For decades, both in popular culture and even in introductory biology, lactate (often incorrectly used interchangeably with “lactic acid”) has been cast as the villain of metabolic processes. The prevailing narrative describes it as a toxic waste product that accumulates when muscles are “starved of oxygen,” leading directly to the burning sensation, fatigue, and muscular failure associated with intense exercise.
As the podcast correctly points out, this view is fundamentally flawed. The production of lactate is not a metabolic dead-end or a sign of system failure. Instead, it is a sophisticated and essential feature of cellular metabolism, occurring continuously in virtually all cells, including at rest. To understand why, we must first look at the process that precedes it: glycolysis.
The Foundation: Glucose and Glycolysis
Glucose: This is a simple, six-carbon sugar (C6H12O6) that serves as a primary energy source for the body.
Glycolysis: This term literally means “sugar-breaking” (glyco- for sugar, -lysis for breaking). It is a sequence of ten enzyme-catalyzed reactions that take place in the cytosol (the fluid portion) of the cell. The net result of glycolysis is the breakdown of one molecule of glucose into two molecules of pyruvate, a three-carbon compound.
This process yields a small amount of ATP (the cell’s direct energy currency) very rapidly, without any immediate need for oxygen. Once pyruvate is formed, it arrives at a critical metabolic crossroads.
Pyruvate has two primary destinations, and the “choice” between them is not a conscious decision but a matter of substrate availability, enzyme capacity, and chemical equilibrium.
Aerobic Fate (Mitochondrial): Pyruvate can be transported into the mitochondria. Inside, an enzyme complex called pyruvate dehydrogenase (PDH) converts it into acetyl-CoA. This molecule then enters the Krebs cycle (or citric acid cycle), a series of reactions that generate a large amount of ATP through a process that ultimately requires oxygen (oxidative phosphorylation). This is a high-yield but relatively slow process.
Lactate Fate (Cytosolic): Pyruvate can remain in the cytosol and be rapidly converted into lactate by the enzyme Lactate Dehydrogenase (LDH). This is a low-yield but extremely fast process.
The old, incorrect model stated that Fate #2 only occurs when Fate #1 is impossible due to a lack of oxygen (i.e., “anaerobic conditions”). The reality is far more dynamic.
The “decision” to produce lactate is governed by three fundamental principles: enzyme kinetics, chemical equilibrium, and the need to sustain energy production.
This is the central, and most overlooked, reason for lactate production.
Enzymes as Catalysts: Enzymes are proteins that dramatically speed up chemical reactions that would otherwise happen very slowly. They don’t change the outcome of a reaction, but they lower the “activation energy” required to get it started. Think of it as digging a channel through a hill—the water (reactants) will flow to the other side (products) much more easily.
The LDH Reaction: The enzyme Lactate Dehydrogenase (LDH) catalyzes the following reversible reaction:
Pyruvate+NADH+H+⇌Lactate+NAD+
The Law of Mass Action: The direction of a reversible reaction is heavily influenced by the concentrations of reactants and products. However, every reaction also has an inherent equilibrium constant (Keq), which defines the ratio of products to reactants when the reaction has settled. For the LDH reaction, this equilibrium lies overwhelmingly in favor of lactate. The podcast cites a Keq of 1.62×1011, a staggeringly large number that indicates a powerful “pull” towards lactate formation.
What this means: As soon as glycolysis produces pyruvate in the cytosol, the ever-present and fast-acting LDH enzyme immediately converts a large portion of it into lactate. This is not a “backup” plan; it is the immediate, chemically favored outcome. Even at rest, the ratio of lactate to pyruvate in a cell is typically around 10:1. During intense exercise, this can rise to 500:1 or more. Lactate is, by far, the more prevalent molecule of the two in the cytosol.
This is the functional reason why lactate production is essential for high-intensity exercise.
The Glycolysis Bottleneck: One of the key steps in glycolysis requires a coenzyme called nicotinamide adenine dinucleotide (NAD+). During this step, NAD+ accepts electrons and a proton, becoming NADH.
A Finite Supply: The cell has a very limited pool of NAD+. If glycolysis runs at a high rate (as it does during a sprint), all the available NAD+ would be converted to NADH in less than a second.
The Consequence: Without free NAD+, glycolysis would grind to a halt. This would mean the cell’s ability to rapidly produce ATP would cease, leading to immediate muscular failure.
Lactate production is the solution. By converting pyruvate to lactate, LDH uses up the NADH that was generated during glycolysis, thereby regenerating NAD+.
Pyruvate+NADH→Lactate+NAD+
This regenerated NAD+ can now cycle back to be used in glycolysis again, allowing the rapid production of ATP to continue. Lactate production is therefore an essential link that allows glycolysis to run at high speeds, uncoupled from the slower, oxygen-dependent processes in the mitochondria.
Glycolysis is not just for producing ATP for exercise. The intermediate molecules created during the breakdown of glucose are constantly being siphoned off to create other vital compounds, such as:
Ribose for DNA and RNA.
Glycerol for building fatty acids.
Certain amino acids.
Because of these constant demands, there is always a baseline level of activity—or flux—through the glycolytic pathway. And where there is glycolytic flux, there is pyruvate production, and therefore, there is always lactate production.
In summary, lactate is not a metabolic villain or a waste product. It is a crucial molecule whose production is a consequence of fundamental biochemical laws and a necessary component of a robust energy system. We make lactate because:
Chemical Equilibrium Demands It: The enzyme LDH strongly favors the conversion of pyruvate to lactate.
High-Rate Energy Production Requires It: The process regenerates the NAD+ needed to sustain glycolysis during intense effort.
General Metabolism Produces It: The constant background activity of glycolysis for cellular maintenance ensures that lactate is always being made.
Understanding this shifts our perspective entirely. Lactate is not the cause of fatigue, but rather a marker of a high rate of glycolysis. It is a valuable fuel source that can be used by the heart, brain, and other muscles, a topic for another deep dive.