Sep 22, 2025
Electron Carriers
NADH and FADH2 store electrons in covalent bonds.
These electrons can be released:
NADH → NAD⁺ + 2H⁺ + 2e⁻
FADH2 → FAD + 2H⁺ + 2e⁻
Released electrons drive the Electron Transport Chain (ETC).
The Electron Transport Chain (ETC)
Electrons from NADH & FADH2 create a proton (H⁺) gradient by driving protons out of the mitochondrial matrix.
Complexes I, III, and IV are molecular motors (like an electric circuit).
Oxygen is the final electron acceptor.
Proton Gradient and ATP Synthase
The proton gradient drives ATP synthase.
Protons return to the mitochondrial matrix through ATP synthase, causing it to rotate.
This rotational energy phosphorylates ADP → ATP.
Analogy: part of an electric circuit, powered by protons instead of electrons.
ATP Yield from ETC
From 1 molecule of glucose:
10 NADH + 2 FADH2 → ~27 ATP
Pyruvate Fates
Pyruvate has two main energetic fates:
TCA cycle → ~27 ATP per mole of glucose
Lactate → ???
GAPDH and Its Role in Glycolysis
GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) is an enzyme in the middle of glycolysis.
It converts glyceraldehyde-3-phosphate → 1,3-bisphosphoglycerate.
In this step, GAPDH uses NAD⁺ as an electron acceptor and produces NADH.
👉 This means: every time glycolysis runs, it consumes NAD⁺ and generates NADH
For glycolysis to keep going, cells must have a steady supply of NAD⁺.
If NAD⁺ runs out, GAPDH (and therefore glycolysis) stops
High Energy Demand = High Glycolytic Flux
In situations like exercise, sprinting, or high metabolic stress, glycolysis runs very fast.
This produces a lot of NADH.
If NADH accumulates, the pool of NAD⁺ shrinks (since NAD⁺ is converted into NADH).
👉 So the cell risks running out of NAD⁺, which would block glycolysis
Lactate pathway (lactate shunt): Pyruvate is reduced to lactate by lactate dehydrogenase (LDH), and this reaction regenerates NAD⁺ directly in the cytoplasm
High Energy Demand & Lactate Shunt
In sprinting, glycolysis makes NADH faster than the ETC can recycle it.
NAD⁺ runs low → glycolysis risks stopping.
Solution: Lactate dehydrogenase converts pyruvate + NADH → lactate + NAD⁺.
This quickly regenerates NAD⁺ so glycolysis (and ATP production) continues, though inefficiently.