What About The Krebs’ Cycle?

Krebs’ Cycle also known as the Citric Acid Cycle, Tricarboxylic acid cycle (TCA cycle) or the Szent-Györgyi–Krebs cycle which  is a series of enzyme-catalyzed chemical reactions that form a key part of aerobic respiration in cells. It occurs in the matrix of the mitochondria and is used by all aerobic organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and proteins into carbon dioxide. 

In this cycle, Acetyl-CoA splits into CoA which is reused in the link reaction and into an acetyl group. This 2-carbon acetyl group enters the Krebs’ cycle by combining with oxaloacetate. When they react they form a 6-carbon citrate compound. During the Krebs’ cycle a series of decarboxylation reactions and dehydrogenation reactions occur. Hydrogens (H) are accepted by NAD which becomes NADH and Flavine Adenine Dinucleotide (FAD) which becomes FADH. FADH and NADH transport the H atoms to the respiratory chain where large amounts of ATP are manufactured. It is important that oxaloacetate is continuously regenerated in the cycle to ensure that it combines with and acetyl group and enables the removal of H from various intermediates in the Krebs’ cycle. The cycle is split into eight steps.

 Step 1

The acetic acid subunit of acetyl CoA is combined with oxaloacetate to form a molecule of citrate.  The Acetyl-CoA acts only as a transporter of acetic acid from one enzyme to another.  After Step 1, the coenzyme is released by hydrolysis so that it may combine with another acetic acid molecule to begin the Krebs cycle again.

Step 2

The citric acid molecule undergoes an isomerization. A hydroxyl group and a hydrogen molecule are removed from the citrate structure in the form of water. The two carbons form a double bond until the water molecule is added back. The hydroxyl group and hydrogen molecule are reversed with respect to the original structure of the citrate molecule. Thus, isocitrate is formed.

Step 3

In this step, the isocitrate molecule is oxidized by a NAD molecule.  The NAD molecule is reduced by the hydrogen atom and the hydroxyl group. The NAD binds with a hydrogen atom and carries off the other hydrogen atom leaving a carbonyl group. This structure is very unstable, so a molecule of CO₂ is released creating alpha-ketoglutarate.

Step 4

In this step, CoA, returns to oxidize the alpha-ketoglutarate molecule.  A molecule of NAD is reduced again to form NADH and leaves with another hydrogen.  This instability causes a carbonyl group to be released as carbon dioxide and a thioester bond is formed in its place between the former alpha-ketoglutarate and CoA to create a molecule of succinyl-CoA complex.

Step 5

A water molecule sheds its hydrogen atoms to CoA. Then, a free-floating phosphate group displaces CoA and forms a bond with the succinyl complex. The phosphate is then transferred to a molecule of GDP to produce an energy molecule of GTP. It leaves behind a molecule of succinate.

Step 6

Succinate is oxidized by a molecule of FAD. The FAD removes two hydrogen atoms from the succinate and forces a double bond to form between the two carbon atoms, thus creating fumarate.

Step 7

An enzyme adds water to the fumarate molecule to form malate. The malate is created by adding one hydrogen atom to a carbon atom and then adding a hydroxyl group to a carbon next to a terminal carbonyl group.

Step 8

In this final step, the malate molecule is oxidized by a NAD molecule. The carbon that carried the hydroxyl group is now converted into a carbonyl group. The end product is oxaloacetate which then combines with acetyl-CoA and begin the Krebs cycle all over again.

 

Electron Transport Chain

The Krebs’ cycle produces 1 molecule of ATP, 4 pairs of H atoms and 2 molecules of CO2 for every molecule of Acetyl-CoA oxidised. The sequence of reactions in the Electron Transport Chain is as follows:

1. The H donor of NADH2 passes the H to another acceptor, FAD (becomes FADH2).

2. The H atoms are now split into electrons and protons.
3. FADH2 transfers the electrons to the next acceptors called cytochromes (Iron[Fe] containing chromoproteins). The more important is being cytochrome A,B,C and cytochrome oxidase.
4. Electrons from H are first transferred to cytochrome B and this is changed from its oxidised form to the reduced form.
5. Reduced cytochromes then pass their electrons to cytochrome oxidase. Finally, reduced cytochrome oxidase transfers the electrons back to the protons and the H so formed reduced oxygen to water.