Citric Acid Cycle- Kreb Cycle
Under aerobic conditions the end product of glycolysis is pyruvic acid. The next step is the formation of acetyl coenzyme A (acetyl CoA) – this step is technically not a part of the citric acid cycle, but is shown on the diagram on the top left.
Acetyl CoA, whether from glycolysis or the fatty acid spiral, is the initiator of the citric acid cycle. In carbohydrate metabolism, acetyl CoA is the link between glycolysis and the citric acid cycle. The initiating step of the citric acid cycle occurs when a four carbon compound (oxaloacetic acid) condenses with acetyl CoA (2 carbons) to form citric acid (6 carbons).
The whole purpose of a “turn” of the citric acid cycle is to produce two carbon dioxide molecules. This general oxidation reaction is accompanied by the loss of hydrogen and electrons at four specific places. These oxidations are connected to the electron transport chain where many ATP are produced.
Step 1
The acetic acid subunit of acetyl CoA is combined with oxaloacetate to form a molecule of citrate. The acetyl coenzyme A 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. Only now, 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, coenzyme A, 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 alphaketoglutarate and coenzyme A to create a molecule of succinyl-coenzyme A complex.
Step 5
A water molecule sheds its hydrogen atoms to coenzyme A. Then, a free-floating phosphate group displaces coenzyme A 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
In this step, succinate is oxidized by a molecule of FAD (Flavin adenine dinucleotide). 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 can then combine with acetyl-coenzyme A and begin the Krebs cycle all over again.
Summary of Krebs Cycle
In summary, three major events occur during the Krebs cycle. One GTP (guanosine triphosphate) is produced which eventually donates a phosphate group to ADP to form one ATP; three molecules of NAD are reduced; and one molecule of FAD is reduced. Although one molecule of GTP leads to the production of one ATP, the production of the reduced NAD and FAD are far more significant in the cell’s energy-generating process. This is because NADH and FADH2 donate their electrons to an electron transport system that generates large amounts of energy by forming many molecules of ATP.
