Cellular Respiration: NADH, Krebs Cycle, and Electron Transport Chain

NADH — how many are produced by glycolysis, and what is its purpose?

2 NADH per glucose (or glycogen). Purpose: carries high-energy electrons/hydrogens either to the mitochondria to fuel the ETC (aerobic) or to pyruvate to form lactate (anaerobic).

NAD+ reconversion — ANAEROBIC pathway

Pyruvate + NADH + H+ → Lactate + NAD+ (enzyme: lactate dehydrogenase).

NAD+ reconversion — AEROBIC pathway

NADH → (mitochondrial shuttle: glycerol-phosphate or malate-aspartate shuttle) → electrons enter the ETC at Complex I → NAD+ is regenerated.

Why must NAD+ be regenerated during glycolysis?

Because the glyceraldehyde 3-phosphate step of glycolysis requires NAD+ to accept hydrogens; without regeneration, NAD+ would run out and glycolysis would stop.

FAD / FADH2

A second electron/hydrogen carrier (from riboflavin, vitamin B2); enters the ETC later than NADH, at Complex II, yielding less ATP per molecule (1.5 vs. 2.5).

3 stages of aerobic ATP production (simple version)

1) Chop food into acetyl-CoA. 2) Run acetyl-CoA through the Krebs cycle to squeeze out NADH/FADH2 'batteries' (+ release CO2). 3) Feed those batteries into the electron transport chain, where oxygen accepts the spent electrons and ATP synthase cranks out ATP.

Oxidative phosphorylation

The process/term for aerobic ATP production — the combined action of the citric acid cycle and electron transport chain, occurring in the mitochondria.

Triglyceride metabolism pathway

Triglyceride → (lipase/lipolysis) → 3 Fatty Acids + Glycerol. Fatty acids → (beta oxidation, in mitochondria) → Acetyl-CoA → Krebs cycle. Glycerol travels to the liver to be converted to glucose; it contributes little direct fuel to muscle.

Beta oxidation

The mitochondrial process that breaks fatty acids down into 2-carbon acetyl-CoA fragments so they can enter the Krebs cycle.

How are amino acids prepared for oxidative phosphorylation?

They undergo deamination/transamination, which removes the nitrogen-containing amine group, leaving a carbon skeleton that enters as pyruvate, acetyl-CoA, or a Krebs cycle intermediate.

Where does acetyl-CoA come from?

Three sources: (1) pyruvate, via the pyruvate dehydrogenase complex; (2) fatty acids, via beta oxidation; (3) certain (ketogenic) amino acids, after deamination.

Purpose of the Krebs cycle

To complete the oxidation (electron/hydrogen removal) of acetyl-CoA — from carbs, fats, or proteins — using NAD+ and FAD as carriers, so those electrons can later drive ATP production in the ETC.

NADH and FADH2 produced per turn of the Krebs cycle

One turn (one acetyl-CoA) produces 3 NADH + 1 FADH2 + 1 GTP. Per glucose (2 acetyl-CoA = 2 turns): 6 NADH + 2 FADH2 + 2 GTP total.

NADH from pyruvate → acetyl-CoA conversion (separate from the Krebs cycle count)

2 NADH total (1 per pyruvate) — produced during the conversion step, before the Krebs cycle even begins.

Role of NADH/FADH2 from the Krebs cycle

They transport the high-energy electrons and H+ removed during oxidation to the inner mitochondrial membrane, handing them off to the electron transport chain.

Isocitrate dehydrogenase

The rate-limiting enzyme of the Krebs cycle; inhibited by ATP, stimulated by ADP and calcium.

GTP in the Krebs cycle

An energy-rich compound formed directly in the Krebs cycle (substrate-level phosphorylation) that transfers its terminal phosphate to ADP to form ATP — 1 GTP per turn, 2 per glucose.

Role of NADH/FADH2 in the ETC

They donate their high-energy electrons (and H+) to the ETC protein complexes — NADH enters at Complex I, FADH2 enters later at Complex II.

How do NADH/FADH2 ultimately create ATP? (chemiosmosis)

As electrons pass down the complexes, energy released pumps H+ from the matrix into the intermembrane space, building a proton gradient. H+ flowing back through ATP synthase drives ATP formation from ADP + Pi.

Role of electrons in the ETC — where do they come from?

Electrons power the proton pumping at each complex; they come from the hydrogen atoms carried by NADH and FADH2.

Role of oxygen in the ETC

Oxygen is the final electron acceptor, at Complex IV — it combines with spent electrons and H+ to form water (H2O), keeping the chain from backing up/stalling.

Cytochrome c oxidase

The rate-limiting enzyme of the electron transport chain (located in Complex IV); inhibited by high ATP, stimulated by rising ADP.

ATP synthase

The enzyme that produces ATP as H+ flows back through it into the mitochondrial matrix, down the proton gradient built by the ETC.