Why does FADH‌2‌‌ ‌Yield‌ ‌Less‌ ‌ATP‌ ‌Than ‌NADH?‌ ‌

Why‌ ‌Does‌ ‌FADH‌2‌‌ ‌Yield‌ ‌Less‌ ‌ATP‌ ‌Than ‌NADH?‌ ‌

FADH‌2‌‌ ‌Yield‌ ‌Less‌ ‌ATP‌ ‌Than ‌NADH because complex II of the electron transport chain does not pump out protons during oxidative phosphorylation. 

ATP (Adenosine Triphosphate) is the general currency of energy in cells, it is what living cells utilize for activities requiring energy, like muscle contraction; molecules biosynthesis; and movement of flagella. Although a few of the ATP utilized by cells is produced by substrate-level phosphorylation, the majority is produced by oxidative phosphorylation which requires the utilization of FADH2 and NADH at the electron transport chain, when one molecule of each of the duo is passed through the chain, FADH2 yields less ATP than NADH, why?

Taking the human body into consideration, we need energy in form of ATP for running normal bodily functions and movements, where does the energy come from? Food, alright. When we eat food, there occurs digestion in the gut, the food molecules are then absorbed into our cells, this is called primary metabolism. Inside the cells, the absorbed molecules undergo secondary metabolism to generate FADH2 and NADH among other substituents. The FADH2 and NADH produced are then taken into mitochondria to generate ATP through tertiary metabolism.

What is Mitochondrion?

Mitochondrion (plural: mitochondria) is the powerhouse of a cell, it is responsible for the production of energy in eukaryotic cells in the form of ATP. Ovoid in shape, it has a matrix enclosed by an inner selective membrane and an outer more permeable one, the two membranes are separated by the intermembranous space.

The inner membrane has in-foldings called cristae which exhibit a high degree of selective permeability and serve as the home for a group of enzymes and co-enzymes constituting the electron transport chain, this chain is where FADH2 and NADH are used to produce the ATP.

The Electron Transport Chain….

Otherwise called the respiratory chain is a cluster of enzymes and co-enzymes consisting of four fixed complexes (reads: Complex I, II, III & IV) and two mobile carriers (Co-Q and Cyt-C).

Complex I is the NADH dehydrogenase complex, it removes one H ion and two electrons from NADH (giving NAD+)  and pumping 4 protons from the matrix into the intermembranous space. 

Complex II is the receptor of the electrons from FADH2 to give FAD, this complex does not pump protons to the intermembranous space. 

Complex III receives the electrons that passed through either of the first two complexes and pump out 4 protons into the intermembranous space. 

Complex IV takes the electrons from complex III and use the energy to pump 2 protons into the space. 

Co-enzyme Q (Co-Q) and Cytochrome-C (Cyt-C) serve as carriers of electrons between the complexes. 

How does it Work? 

The FADH2 and NADH that are generated in secondary metabolism are transported to the inner mitochondrial membrane where they give up their H ions to the almighty course of ATP synthesis in the following steps:

  1. NADH (Nicotinamide Adenine Dinucleotide) gives up two electrons and a proton to complex I, through a series of reactions in the complex, four protons are forcefully thrown out of the matrix into the intermembranous space. 
  2. FADH2 (reduced Flavin Adenine Dinucleotide) transfers its electrons to complex II, this complex receives the electrons and gives them out to the Co-Q effortlessly, it does not pump electrons out of the matrix. 
  3. Co-Q collects the electrons from either complex I or II and passes them to complex III. 
  4. At complex III, four protons are expelled from the matrix by the virtue of the energy produced by the passage of the received electrons. 
  5. Cyt-C carries the electrons from complex III to IV. 
  6. Complex IV receives the electrons and liberate them to produce H2O, it pumps 2 protons in return. 

One might ask, why are protons pumped at complexes I, III, and IV into the intermembranous space? Well, this brought us to the last station of ATP production: the ATP Synthase

What is ATP Synthase and How does it Work? 

The ATP synthase is a channel through only which protons can enter the matrix across the inner mitochondrial membrane, it is the machine enzyme responsible for the phosphorylation of ADP (Adenosine Diphosphate) to give ATP. 

When protons (H+) are pumped out of the matrix, the H+ concentration in the intermembranous space becomes very high making that of the matrix relatively low, this creates a gradient that favors the downhill translocation of the protons, remember the inner membrane is selectively permeable? The protons could only pass through the ATP synthase. When the H+ are passing down to the matrix, the ATP synthase uses the energy they dissipate to link ADP with Pi producing ATP. 

It was estimated that for every 3 protons that passed through the ATP synthase, one molecule of ATP is produced. So, the amount of ATP produced by NADH or FADH2 depends on the number of protons each helps to be pumped during oxidative phosphorylation

Oxidative Phosphorylation? Yes, oxidation is the removal of H ions, when NADH and FADH2 give their H ions to the electron transport chain, oxidation happens! An increase in the concentration of protons outside the inner mitochondrial membrane is the fruition of this oxidation. Phosphorylation is what happens at the ATP synthase: adding inorganic phosphate (Pi) to ADP. Simple. 

Are we safe to say that NADH and FADH2 undergo oxidative phosphorylation to give ATP? Then, why does FADH2 yield less ATP than NADH? The computation goes…. 

The Calculation…

  • For NADH 
  • 4 protons are pumped at complex I 
  • 4 protons are pumped at complex III 
  • 2 protons are pumped at complex IV. 


A total of 10 protons are pumped. 

If 3 protons are required to produce 1 ATP:

Total protons ÷  Required protons per ATP = Total ATP

10÷3 = 3.334

Approximately, 3 molecules of ATP are produced per NADH molecule.

  • For FADH2
  • 0 protons at complex II
  • 4 protons pumped out at complex III 
  • 2 protons are pumped out at complex IV

0+4+2=6. A total of 6 protons are pumped. 

If 3 protons are required to produce 1 ATP:

Total protons ÷ Required protons to produce 1 ATP = Total ATP


2 molecules of ATP are produced by one molecule of FADH2

The Genesis…

FADH‌2‌‌ ‌Yield‌ ‌Less‌ ‌ATP‌ ‌Than ‌NADH because complex II of the electron transport chain does not pump out protons during oxidative phosphorylation. 

Also read Careers for Introverts in Healthcare

Why does FADH‌2‌‌ ‌Yield‌ ‌Less‌ ‌ATP‌ ‌Than ‌NADH?‌ ‌

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