How a Cell Turns One Glucose Into Dozens of ATP

Glycolysis leaves most of glucose's energy locked inside two molecules of pyruvic acid. With oxygen, the mitochondria break it down completely to carbon dioxide and water.

This part covers the link reaction and Krebs cycle, the electron transport system, the ATP balance sheet, and amphibolic pathways and the respiratory quotient.

**In the mitochondrial matrix, pyruvic acid loses carbon dioxide and joins coenzyme A to form acetyl CoA, which enters the Krebs cycle; each turn releases 2 CO${}_2$, 3 NADH, 1 FADH${}_2$ and 1 GTP, and since one glucose gives two pyruvic acids, all of this doubles per glucose.

Link reaction:**

$$\text{Pyruvic acid}+\text{CoA}+{\text{NAD}}^{+}\underset{{\text{Mg}}^{2+}}{\overset{\text{pyruvate dehydrogenase}}{\to }}\text{Acetyl CoA}+{\text{CO}}_2+\text{NADH}+{\text{H}}^{+}$$

Krebs cycle — key steps:

- Acetyl CoA + oxaloacetic acid (4C) + water $\to$ citric acid (6C), by citrate synthase
- Two decarboxylations form $\alpha$-ketoglutaric acid (5C) and then succinyl CoA — releasing **2 CO${}_2$ and 2 NADH**
- Succinyl CoA $\to$ succinic acid, making 1 GTP
- Succinic acid $\to$ fumaric acid, making **1 FADH${}_2$**
- Malic acid $\to$ oxaloacetic acid, making 1 NADH; the acceptor is regenerated

Worked example — per glucose. Two pyruvic acids give:

$${\text{CO}}_2=2\times (1+2)=6\text{NADH}=2\times (1+3)=8{\text{FADH}}_2=2\text{GTP}=2$$

An everyday example. A traffic roundabout, where cars join and leave but the circle remains, is like the Krebs cycle regenerating oxaloacetic acid.

The substance. The Krebs cycle uses no oxygen directly, yet it stops without oxygen because NAD${}^{+}$ and FAD are not regenerated.

**NADH and FADH${}_2$ pass electrons to carriers in the inner mitochondrial membrane; as electrons move from complex I to complex IV, protons are pumped out, oxygen accepts the electrons to form water, and protons returning through ATP synthase drive ATP formation.

The chain:

- Complex I — NADH dehydrogenase; takes electrons from NADH and passes them to ubiquinone
- Complex II — passes electrons from FADH${}_2$ to ubiquinone
- Complex III** — cytochrome bc${}_1$ complex; receives electrons from ubiquinone
- Cytochrome c — a small mobile protein carrying electrons from complex III to complex IV
- Complex IV — cytochrome c oxidase, with cytochromes a and a${}_3$ and copper centres; hands electrons to oxygen

Oxygen is the terminal acceptor, forming water.

Oxidative phosphorylation. Electron flow pumps protons across the inner membrane. They return through complex V, ATP synthase: **F${}_0$ forms the proton channel in the membrane, and F${}_1$ makes ATP from ADP and phosphate.

Usual yields: each NADH gives 3 ATP; each FADH${}_2$ gives 2 ATP.

An everyday example. A bucket chain passing water hand to hand is like electrons moving carrier to carrier, with oxygen as the last person emptying the bucket.

The substance. This is chemiosmosis again** — the same mechanism as in chloroplasts, but powered by food instead of light.

**Adding the ATP made directly to the ATP from all NADH and FADH${}_2$ gives 38 ATP per glucose, but this figure rests on assumptions — a smooth sequence of pathways, fixed yields, and no intermediates drawn off — so living cells usually make less.

Per glucose:

- Glycolysis — net 2 ATP; 2 NADH
- Link reaction — 2 NADH
- Krebs cycle — 2 GTP; 6 NADH; 2 FADH${}_2$

Worked example — the total.**

$$\text{Direct}=2+2=4\text{NADH}=(2+2+6)\times 3=30{\text{FADH}}_2=2\times 2=4$$

$$\text{Total}=4+30+4=38\text{ ATP}$$

Why 36 is also quoted. If each NADH from glycolysis yields 2 ATP instead of 3:

$$38-2\times (3-2)=36\text{ ATP}$$

The assumptions:

- Pathways run in an orderly sequence, one substrate forming the next
- NADH from glycolysis enters mitochondria for oxidative phosphorylation
- No intermediate is withdrawn to make other compounds
- Only glucose is respired

An everyday example. A monthly budget planned on paper rarely matches real spending, because unplanned costs appear — just as real cells divert intermediates.

The substance. Aerobic respiration nets up to 38 ATP against 2 from fermentation, which is why oxygen-using organisms can sustain far more activity.

Respiration is amphibolic because its pathway both breaks molecules down and supplies building blocks to make them; the respiratory quotient, carbon dioxide released divided by oxygen used, is 1 for carbohydrates, about 0.7 for fats and about 0.9 for proteins, so it reveals the substrate.

Amphibolic pathway:

- Breakdown — fats enter as glycerol (converted to PGAL) and fatty acids (as acetyl CoA); proteins enter as amino acids at pyruvic acid, acetyl CoA or Krebs cycle stages
- Synthesis — acetyl CoA is withdrawn to make fatty acids; Krebs intermediates are used to make amino acids

Respiratory quotient:

$$\text{RQ}=\frac{{\text{volume of CO}}_2\text{ evolved}}{{\text{volume of O}}_2\text{ consumed}}$$

Carbohydrate. Glucose uses 6 O${}_2$ and releases 6 CO${}_2$, so RQ = 6/6 = 1.

Worked example — fat (tripalmitin):

$$2{\text{C}}_{51}{\text{H}}_{98}{\text{O}}_6+145{\text{O}}_2\to 102{\text{CO}}_2+98{\text{H}}_2\text{O}\text{RQ}=\frac{102}{145}\approx 0.7$$

Reading RQ: 1 means carbohydrate; below 1 means fat or protein; above 1 points to anaerobic respiration.

An everyday example. Oil-rich groundnut and mustard seeds show an RQ below 1 as they germinate, while starchy wheat grains show about 1.

The substance. Fats release more energy per gram because they are less oxidised — the same reason their RQ is lower.