The Krebs cycle is a series of eight chemical reactions that your cells use to break down fuel molecules and extract energy from them. It takes place inside mitochondria, the energy-producing structures found in nearly every cell in your body. Also called the citric acid cycle or the TCA cycle, it sits at the center of your metabolism, connecting the breakdown of carbohydrates, fats, and proteins to the production of the ATP your cells run on.
How Fuel Enters the Cycle
The Krebs cycle doesn’t work directly on the food you eat. By the time nutrients reach it, they’ve already been broken down through earlier steps. Glucose, for instance, is first split in half through a process called glycolysis, which produces a molecule called pyruvate. That pyruvate then enters the mitochondria, where a large enzyme complex strips off one of its carbon atoms (releasing it as CO2) and attaches the remaining two-carbon fragment to a helper molecule. The result is acetyl-CoA, the actual fuel that feeds into the Krebs cycle.
Fats and certain amino acids from protein also get converted into acetyl-CoA through their own pathways. This makes the Krebs cycle a universal hub: no matter what type of food you started with, the final stages of energy extraction converge here.
The Eight Steps, Simplified
The cycle begins when the two-carbon acetyl-CoA combines with a four-carbon molecule called oxaloacetate, forming a six-carbon molecule called citrate (this is why it’s also called the citric acid cycle). Over the next seven reactions, enzymes rearrange, strip off carbon atoms, and shuffle electrons, gradually converting citrate back into oxaloacetate so the whole process can repeat.
Here’s what happens in broad strokes:
- Steps 1 and 2: Acetyl-CoA joins oxaloacetate to make citrate, which is then rearranged into a nearly identical molecule called isocitrate.
- Steps 3 and 4: Two consecutive reactions each strip off one carbon atom as CO2. These are the steps that release the carbon you originally ate as carbon dioxide, which you eventually exhale. Both reactions also capture high-energy electrons by loading them onto carrier molecules (NADH).
- Step 5: The thioester bond in the remaining molecule is broken, and the released energy is used to make one GTP, which is functionally equivalent to one ATP.
- Steps 6, 7, and 8: The molecule is progressively oxidized and reshaped back into oxaloacetate. One of these steps loads electrons onto a different carrier (FADH2), and another produces one more NADH.
By the end, oxaloacetate is regenerated and ready to grab another acetyl-CoA, keeping the cycle spinning.
Energy Output Per Turn
Each turn of the Krebs cycle processes one acetyl-CoA and produces 3 NADH, 1 FADH2, 1 ATP (as GTP), and 2 molecules of CO2. Those numbers may look modest, but the real payoff comes next. NADH and FADH2 carry their electrons to the inner mitochondrial membrane, where a chain of proteins uses them to generate large amounts of ATP through oxidative phosphorylation.
Because each glucose molecule produces two pyruvates, the cycle turns twice per glucose. That means one glucose generates 6 NADH, 2 FADH2, and 2 ATP from the Krebs cycle alone. When those electron carriers are cashed in at the next stage, a single glucose molecule ultimately yields roughly 30 to 32 ATP total across the entire process of cellular respiration. The Krebs cycle is where most of those electron carriers are loaded up.
More Than Just Energy
Calling the Krebs cycle an “energy factory” is accurate but incomplete. Several of its intermediate molecules serve as raw materials for building other things your body needs. Citrate can be pulled out of the cycle and used to build fatty acids. Alpha-ketoglutarate is a precursor for the amino acids glutamate, proline, and arginine. Oxaloacetate feeds into the production of aspartate and asparagine. Succinyl-CoA provides the backbone for porphyrins, the ring-shaped molecules at the core of hemoglobin.
Acetyl-CoA itself is a starting point for cholesterol, vitamin D, and steroid hormones. So the cycle acts as a metabolic crossroads: molecules flow in and out depending on what the cell needs at any given moment, not just energy but structural and signaling molecules too.
B Vitamins Keep It Running
Several B vitamins are essential for the Krebs cycle to function because they form part of the enzymes and carrier molecules involved. Vitamin B1 (thiamine) is required by both the enzyme that converts pyruvate into acetyl-CoA and the enzyme that handles the fourth step of the cycle. Vitamin B2 (riboflavin) is the basis of FAD, the electron carrier that gets reduced to FADH2 during step six. Vitamin B3 (niacin) is the precursor of NAD, the carrier behind all three NADH molecules produced per turn.
A deficiency in any of these vitamins can slow the cycle and impair energy production. This is part of why severe B vitamin deficiencies cause fatigue, neurological problems, and muscle weakness: the cells literally can’t extract energy from food efficiently.
How Cells Control the Cycle’s Speed
Your cells don’t run the Krebs cycle at a fixed rate. When energy demand is high, like during exercise, the cycle speeds up. When ATP is abundant and the cell doesn’t need more, it slows down. This regulation happens primarily at three enzyme-controlled steps: the first (citrate synthase), the third (isocitrate dehydrogenase), and the fourth (alpha-ketoglutarate dehydrogenase). High levels of ATP and NADH signal the cell to ease off, while high levels of ADP (a sign that ATP has been used up) signal it to ramp up.
What Happens When the Cycle Breaks
Genetic mutations that disable Krebs cycle enzymes are rare but severe. Fumarase deficiency, which affects the seventh step, typically causes profound developmental delay and neurological damage in infants. Some cases follow a rapidly fatal course within the first two years of life, while others present as a slower-progressing brain disease with severe speech delay. In adults, carrying one mutated copy of the fumarase gene (rather than two) is linked to hereditary leiomyomatosis and renal cell carcinoma syndrome, which involves skin and uterine growths along with an aggressive form of kidney cancer.
Defects in the enzyme at step five (succinyl-CoA synthetase, encoded by the SUCLA2 or SUCLG1 genes) produce a different pattern. These mutations cause mitochondrial depletion syndromes, characterized by severe low muscle tone, progressive movement disorders, muscle wasting, and sensorineural hearing loss. Another condition, 2-oxoglutaric aciduria, disrupts the fourth step and leads to chronic metabolic acidosis, severe microcephaly, and intellectual disability.
These disorders highlight how central the Krebs cycle is to normal development. The brain and muscles, tissues with the highest energy demands, are consistently the most affected when the cycle can’t function properly.