Why does FADH2 form two ATPs

As Cellular respiration, biological oxidation or internal breathing those metabolic processes are referred to, which serve the energy gain of the cells. In particular, this means the biochemical processes of the respiratory chain in the inner membrane of the mitochondria, at the end of which ATP is synthesized. Other forms of breathing - in the sense of gas exchange between organisms - are summarized under the term external breathing.


The following shows the use of energy from the oxidation of glucose (grape sugar) by cells. Cells can also obtain energy through the oxidation of other substances, but the oxidation of glucose is the most common source of energy.

Cells take up glucose for their energy supply. It is completely broken down by eukaryotes in the cytoplasm and mitochondria into carbon dioxide and water:

C.6H12O6 + 6 O2 → 6 CO2 + 6 H.2O

The change in free energy under standard conditions, pH 7 instead of 0, is ΔG in this reaction0'= - 2822 kJ per mole of glucose. The following standard conditions were agreed: temperature 25 ° C, pressure 1.013 bar, concentration of the substances (reactants) involved in the reaction 1 mol / L with the exception of that of water, for which 55.6 mol / L (pure water) has been agreed, and that of gases for which a concentration in solution equilibrium with a partial pressure of 1 bar in the gas phase has been agreed. In the case of biological systems, however, the H.+Ion concentration is not agreed to be the unacceptable concentration of 1 mol / L corresponding to pH 0, which is unsuitable for almost all living beings, but 10-7 mol / L corresponds to pH 7. If the actual conditions deviate from these standard conditions, the amount of change in free energy is also different; it can deviate considerably from the standard value. In living systems, standard conditions are usually not given and often change during the conversion of substances. The amount of change in the free energy under standard conditions therefore only provides an indication of the energy released during a chemical conversion in living beings.

During this chemical conversion, hydrogen atoms are separated from the breakdown products of the glucose molecules in a series of complicated reaction steps - including many redox reactions - and transported to the mitochondria with the help of hydrogen carriers (nicotinamide adenine dinucleotide, NAD). There the hydrogen atoms within the respiratory chain react with oxygen to form water ("biological oxyhydrogen reaction"); the glucose molecules are ultimately completely oxidized. At the end of the breakdown process, the cell uses the energy released during biological hydrogen oxidation to obtain the high-energy compound adenosine triphosphate (ATP). It is required as a universal source of energy for many metabolic processes.

The comprehensive reaction equation for cellular respiration corresponds, read from right to left, to the reaction equation for oxygenic photosynthesis.

Process flow

Cell respiration is a process in which high-energy substances are broken down into low-energy substances. In the case of cellular respiration, the most common glucose molecule is C.6H12O6 in four steps to a C1 body (CO2) and water (H2O) oxidized:

  1. glycolysis,
  2. oxidative decarboxylation
  3. the citric acid cycle and
  4. the end oxidation in the respiratory chain.

The overall balance of cellular respiration looks like this:

C.6H12O6 + 6 O2 → 6 CO2 + 6 H.2O

During this process, the change in free energy (Gibbs energy) under standard conditions, but pH 7 (instead of pH 0), amounts to a total of 2822 kJ / mol.


Glycolysis (= sugar breakdown) takes place in the cytoplasm. During this process, the glucose molecule is first split into two C3 bodies. This happens through double phosphorylation, i.e. elimination of an H and addition of a phosphate residue (P), so that only glucose-6-phosphate (C6H11O6P) arises (through structural changes this is converted into fructose-6-phosphate) and then fructose 1,6-bis-phosphate (C.6H10O6PP). As a result of the phosphorylation, glucose is now in the activated state. This C6 body is then broken down into one molecule of dihydroxyacetone phosphate (DHAP) and one molecule of glyceraldehyde-3-phosphate (GAP) (both C.3H5O3P) split. Only the glyceraldehyde-3-phosphate can be used further, which is why the dihydroxyacetone phosphate is converted into this. So there are always two glyceraldehyde-3-phosphate in the further breakdown. Another phosphate is deposited and the molecule is oxidized, producing 1,3-bisphosphoglycerate (C.3H4O4PP) is created. The electrons are transferred to the hydrogen carrier NAD+ (Nicotinamide adenine dinucleotide in the oxidized form). In the next step, a phosphate residue (P) is transferred to ADP, so that ATP and 3-phosphoglyceric acid (PGS, C.3H5O4P) arise. By splitting off water, phosphoenolpyruvate (PEP, C3H3O3P). In the last step, the last phosphate residue (P) is also transferred to ADP, so that pyruvic acid (pyruvate) (C.3H4O3) and ATP arise.

Glycolysis balance

C.6H12O6 + 2 NAD+ + 2 ADP + 2 P → 2 C3H4O3 + 2 NADH + 2 H+ + 2 ATP

Oxidative decarboxylation

Oxidative decarboxylation is a short step, but it is essential for the next step. In eukaryotes it takes place in the mitochondrial matrix. A complex reaction mechanism turns pyruvic acid into CO2 split off (decarboxylation) and 2 H atoms on NAD+ transferred (redox reaction) and the resulting acetic acid (acetate) bound to the coenzyme A (CoA), so that acetyl-CoA is formed.

Balance of the oxidative decarboxylation:

2 C3H4O3 + 2 NAD+ + 2 CoA → 2 CH3CO-CoA + 2 CO2 + 2 NADH + 2 H+

Citric Acid Cycle (or Citric Acid Cycle)

The citric acid cycle, also known as the tricarboxylic acid cycle, takes its name from the first product that is created, namely citric acid, which has three carboxyl groups. In the last step of the citric acid cycle, oxaloacetic acid (C.4H4O5). Only it is able to combine with acetyl-CoA and, by absorbing water and splitting off CoA, citric acid (C.6H8O7) to build. This means that coenzyme A is regenerated again. Once again, CO2 split off and a reducing equivalent of NADH and α-ketoglutaric acid (C.5H6O5) educated. In the next step, CO is again split off2 and the formation of NADH with the help of coenzyme A. The C3 body that went into the reaction was only completely split at this point. The next steps only serve the formation of oxaloacetic acid so that the cycle can start all over again. This happens via the succinic acid-CoA (C.4H5O3-CoA), succinic acid (C4H6O4), Fumaric acid (C.4H4O4), Malic acid (C.4H6O5) and then by oxidation (formation of a reduction equivalent) to oxaloacetic acid.

Balance of the tricarboxylic acid cycle (runs twice, since 2 moles of pyruvic acid and thus also 2 moles of Acetyl-CoEnzymA are formed from 1 mole of glucose):

C.2H3O-CoA + 3 NAD+ + FAD + ADP + P + GDP + P + 2H2O → 2 CO2 + 3 NADH + 3 H+ + FADH2 + ATP + GTP + CoA

End oxidation in the respiratory chain

The previous process resulted in 4 ATP. Most of the ATP yield, however, is supplied by the respiratory chain with the help of the reduction equivalents. There are a total of 10 NADH (two from glycolysis and eight (2 times 4) from the citric acid cycle) and 2 FADH2 (Flavin adenine dinucleotide) available.

One NADH can have 2 electrons (e), whereby the hydrogen bound to the NAD is released as a proton (H+) becomes free and the remaining NAD molecule is positively charged: NAD+. Because the 2 electrons released in this way are at a very high energy level (very low redox potential of the redox couple NADH / NAD+), 10 protons can be transported from the matrix into the intermembrane space with their help. This happens as follows: The 2 electrons of the NADH reduce the first complex (complex I) of several enzyme complexes of the respiratory chain, which are located between the matrix and the intermembrane space of the mitochondrion. Each electron is then passed on from one enzyme complex to the next via redox reactions. Due to the transfer of electrons from complex to complex, this process is also known as the electron transport chain. Through the complex I, the complex III and the complex IV H+-Ions (protons) are translocated from the matrix into the intermembrane space. This creates a high concentration of hydrogen ions in the intermembrane space, resulting in a pH value below 7 and an osmotic potential. The redox reactions and the creation of the osmotic potential together are called chemiosmosis: The redox reactions are chemical reactions, the difference is the H+-Concentrations of matrix and intermembrane space represent an osmotic potential.

The hydrogen ions finally flow back from the intermembrane space into the matrix space through the membrane-bound ATP synthase. The flow energy is used to bind a phosphate residue to ADP. The oxidation of one NADH creates 3 ATP. The two NADH from glycolysis are an exception. These are still in the cytoplasm and must first be transported into the mitochondria. therefore only 2 ATPs are obtained from each of these. Since 8 + 2 NADH are oxidized, a total of 8 × 3 + 2 × 2 = 28 ATP is created.

With the FADH2 the process works the same in principle, only there is FADH2 electrons at a higher redox potential, i.e. lower energy level, and therefore only enter the respiratory chain at an energetically lower level. Therefore, with the help of the electrons of the FADH2 only 4 protons are pumped from the matrix into the intermembrane space. With an FADH2 therefore only 2 ATP are formed. Since two FADH2 are oxidized, this creates 4 ATP.

The protons and electrons of the NADH and the FADH2 (24 each in total) are combined with 6 O2, which are transported through the membrane into the mitochondrial matrix, to 12 H2O oxidizes. The electron or hydrogen carrier NAD+ and FAD can be achieved by adding 2 e and 2 H+ back to NADH or FADH2 be reduced.

Balance of the respiratory chain:

10 NADH + H+ + 2 FADH2 + 32 (ADP + P) + 6 O2 → 10 NAD+ + 2 FAD + 12H2O + 32 ATP

Energy balance

step Coenzyme Yield ATP yield ATP source
Glycolysis preparatory stage −2 Energy used to break down glucose into 2 molecules of glyceraldehyde-3-phosphate
Glycolysis yield level 4 Substrate chain phosphorylation
2 NADH 4 Oxidative phosphorylation. Just 2 ATP per NADH / H+because these are in the cytoplasm
Oxidative decarboxylation 2 NADH 6 Oxidative phosphorylation
Citric acid cycle 2 Substrate chain phosphorylation
6 NADH 18 Oxidative phosphorylation
2 FADH2 4 Oxidative phosphorylation
maximum possible total yield36 ATP per molecule of glucose

Categories: Biochemical Reaction | metabolism