Hey guys, this is Hazel-Ann and Aaliyah and we’ll be taking over this week. We’re so excited to talk about the TCA and ETC! Week 8 has truly been interesting since we had only quizzes during our lecture time…YIKES!!!!!

Okay so back to the topic….TCA: have you ever wondered why it’s called TCA instead of TAC? I mean after all it stands for Tricarboxylic Acid Cycle right??

Baffled yet??…wait there’s more: this cycle actually has two other names: Citric Acid Cycle and Krebs Cycle!

The Citric Acid Cycle is a sequence of enzyme-catalyzed chemical reactions which are imperative in aerobic respiration in cells.

  • The cycle begins with the end product of glycolysis (the first step of cell respiration), pyruvate.
  • In glycolysis, glucose is decomposed into pyruvate.
  • A two carbon fragment of pyruvate is used to form acetyl coenzyme A. The acetyl-CoA enters the Krebs cycle which occurs in the mitochondria.
  • In the process of converting pyruvate to acetyl-CoA, carbon dioxide is produced and a molecule of NADH is formed.

Step 1:

A molecule of citrate is formed by the joining of the Acetic acid subunit of acetyl CoA with oxaloacetate.  The function of acetyl coenzyme A is to transport acetic acid from one enzyme to another. After this, the Krebs Cycle is restarted when hydrolysis releases the coenzyme so it may combine with another acetic acid molecule.

Step 2:

Then, citric acid molecule goes through an isomerization.  Water is removed from the citrate structure but a double bond forms between the 2 carbons and the water molecule is reintroduced. However, unlike the first citrate molecule structure, the hydroxyl group and hydrogen molecule are transposed. Hence, Isocitrate is forms.

Step 3:

Oxidization of the isocitrate molecule occurs by a NAD molecule that is reduced by the H atom and the OH group. NAD binds with a hydrogen atom and carries off the other hydrogen atom leaving a carbonyl group.  Due to the instability of structure a CO2 molecule is released forming alpha-ketoglutarate.

Step 4:

Here, coenzyme A, reappears and oxidizes alpha-ketoglutarate.  NAD reduction occurs again producing NADH and another H atom remains. Again, a carbonyl group is released as carbon dioxide and is replaced by a thioester bond between the previous alpha-ketoglutarate and coenzyme A while a molecule of succinyl-coenzyme A complex is produced.

Step 5:

Hydrogen atoms from a water molecule are attached to coenzyme A. Coenzyme A is then displaced by a free phosphate group which transfers to a GDP molecule to yield a GTP energy molecule. A succinate molecule remains.

Step 6:

Flavin adenine dinucleotide (FAD) oxidizes succinate removing two H atoms from it and forms a double bond in between the two C atoms, making fumarate.

Step 7:

Malate is formed by the addition of water to the fumarate by an enzyme.

Step 8:

An NAD molecule oxidizes the malate molecule. The OH carrying carbon is transformed into a carbonyl group.  Oxaloacetate is the end product. It can then join acetyl-coenzyme A and resart the Krebs cycle.


In summary, Krebs cycle involves 3 major activities.

1)      Production of 1 GTP (guanosine triphosphate) which eventually donates a phosphate group to ADP to form 1 ATP;

2)      Reduction of 3 NAD molecules;

3)      Reduction of 1 FAD molecule.

In the cell’s energy-generating process, formation of reduced NAD and FAD are more imperative than 1 molecule of GTP producing 1 ATP because NADH and FADH2 give their electrons to the electron transport chain (ETC) that creates a lot of energy by making a lot of molecules of ATP.

If it’s too much to digest right now how about this?


So let’s move on!


Now, the electron transport or respiratory chain is where electrons are transported to join oxygen from respiration at the end of the chain. The overall ETC reaction is:

2 H+ + 2 e+ + 1/2 O2 —> H2O + energy

Pre-Initiation of Electron Transport Chain:

Figure 3: simplified illustration of ETC

ETC is started by oxidation reaction of an organic metabolite with the coenzyme NAD+ (nicotinamide adenine dinucleotide). 2 hydrogen atoms are removed from the organic metabolite which is usually from the citric acid cycle and fatty acids oxidation:

MH2 + NAD+ —–> NADH + H+ + M: + energy, where M= any metabolite (usually an alcohol oxidized to a ketone).

Removal of one hydrogen with 2 electrons as a hydride ion (H) and another as the positive ion (H+) occurs.

NAD+ is a coenzyme containing the B-vitamin, nicotinamide.

The other steps in the ETC are:
1) to pass along 2H+ ions and 2e to eventually react with oxygen;
2) to save energy by forming 3 ATPs; and
3) to restore the coenzymes back to their original form as oxidizing agents.

Initiation of Electron Transport Chain:

  • NADH interacts with the first complex 1 enzyme, known as NADH reductase. Complex 1 contains a coenzyme flavin mononucleotide (FMN), similar to FAD.
  • The NADH, and another hydrogen ion then enter the enzyme complex and pass along the 2 hydrogen ions into the mitochondrial interspace. Acting as a pump, these H atoms are used by ATP synthetase to form an ATP for every two hydrogen ions produced.
  • Performing similar to this, three complexes (1, 3, and 4) produce 2 hydrogen ions each, therefore 3 ATP are produced for every use of the complete ETC.
  • NADH passes along 2 electrons to FMN, iron-sulfur protein (FeS), and lastly to coenzyme Q. These reactions restore coenzyme NAD+ and create a cycling effect. The NAD+ is then ready to react further with metabolites in the TCA cycle.
  • Coenzyme Q makes CoQH2 by joining 2 H ions and is soluble in the lipid membrane and moves through the membrane to encounter enzyme complex 3.
  • Enzyme complex 1 of the ETC is combined with the formation of ATP:

a) MH2 + NAD+ —> NADH + H+ + M + energy

b) ADP + P + energy —> ATP + H2O


Figure 4: Illustration of ETC in mitochondria and the association with TCA Cycle.


Enzyme Complex 3:

  • Cytochrome reductase bc is a series of activities through enzyme complex 3 that begins when CoQH2 carries 2 extra electrons and 2 extra hydrogen ions.
  • Cytochromes are similar in structure to myoglobin or hemoglobin. The heme structure containing the iron ions, initially in the +3 state and changed to the +2 state by the addition of an electron is significant. The CoQH2 passes along the 2 electrons first to cytochrome b1 heme to b2 heme, to an iron-sulfur protein, then to cytochrome c1, and finally to cytochrome c.
  • The 2 hydrogen ions are directed to the inside of the mitochondria for conversion into ATP.


Figure 5: Illustration of cytochrome b, c complex 3.

Complex 4:

  • Cytochrome c is a small molecule able to travel in the lipid membrane layer and diffuses toward cytochrome a complex 4.
  • The transport of the electrons continues, and this is the third and last time that 2 hydrogen ions are directed to the inside of the mitochondria for ATP conversion.
  • ATP synthetase is found throughout the bilayer membrane of the mitochondria. The pumping of the re-entry of the hydrogen ions through the ATP synthetase produces 3 ATP.
  • Finally, diffusion of oxygen into the cell and mitochondria occurs for the last metabolic reaction. A water molecule is produced by reaction of oxygen atom with the 2 electrons and 2 hydrogens.


  • The tricarboxylic acid cycle got the common name “Krebs’ cycle” after the biochemist Hans Adolph Krebs when he discovered the steps of the cycle through a series of experiments, in 1937.
  • This cycle is the second of three parts in the process of breaking down glucose into energy that the body can use, in the form of ATP. The stage before TCA is glycolysis and the stage after is oxidative phosphorylation.
  • The Electron Transport Chain (ETC), while it is the last step of the three in gaining energy from the foods we eat, it is actually THE most important step since most of the ATP is produced here.
  • In glycolysis, the final net production of ATP molecules is 2, in the citric acid cycle, it is 2 and in the electron transport chain, the net production of ATP is 32 ATP molecules. In total, 36 ATP molecules are formed from the entire process during aerobic respiration per pyruvate molecule.
  • In ETC electrons move from high energy to low energy making a proton gradient that then pushes the production of ATP.
  • Altogether TCA and ETC are ESSENTIAL for human survival, since these stages to produce ATP give us energy to carry out our daily activities. ATP is also important in synthesizing RNA and DNA.

So that’s all for this week peeps…thanks for tuning in, hope that this was helpful! Don’t forget to check us for our next post, next week same time.



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