Krebs Cycle — What is It, Steps and Importance

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Krebs Cycle

The Krebs cycle, also known as the TCA (tricarboxylic acid) process or the citric acid cycle, is an essential metabolic cycle in living organisms and provides energy for cellular functions and biological reactions.

It is a series of chemical reactions that forms carbon dioxide and water due to aerobic respiration in a process involving the breakdown of acetyl coenzyme A (acetyl CoA) to make NADH, FADH 2, and ATP.

The Krebs cycle is characteristic of carbohydrate metabolism in cells, with the various steps being carried out in different parts of an organelle called mitochondria. The carbon atoms come from carbon dioxide breathed into the body or taken from food during respiration.

For this series of chemical reactions to occur, one essential compound needs to be built up: Acetyl coenzyme A (acetyl-CoA). This compound is made by adding a molecule of Biotin onto Pyruvate, which forms Acetyl-CoA.

The Krebs Cycle Steps

1. Acetyl CoA is the first compound that enters the Krebs cycle and is made by adding a molecule of Biotin onto Pyruvate, which forms acetyl-CoA.

2. The next step in the Krebs cycle starts with Aconitase, an enzyme that helps remove hydrogens from Citrate to make Isocitrate.

3. After this, Isocitrate dehydrogenase converts Isocitrate into α -Ketoglutarate (αKG).

4. Once again, we see another enzyme, Succinyl Coenzyme A transferase (succinyl Co), helping us move on to the next step by converting succinyl CoA into succinate.

5. The enzyme Oxoglutarate dehydrogenase (αKG) catalyzes α-Ketoglutarate to become Glutamate.

6. This is where our cycle continues in full swing, with the help of another enzyme, ATP synthase, which forms an ATP molecule out of inorganic phosphate and ADP molecules.

7. The next step involves Succinate dehydrogenase that turns both Fumarate into Succinate for us to continue this process…again!

8. Finally, we come upon the last part of this cycle, where Fumarase helps us put water onto Fumarate to make malate and another succinate molecule.

9. The enzyme Malate dehydrogenase can convert malate into oxaloacetcata, with the help of NADH… who would have thought!?

10. Now that we have an oxaloacetate molecule, it's time for the cycle to complete itself by adding a compound called Acetyl-CoA onto an acetyl group for this cycle to start all over again! Don't forget about ATP synthase! This step also involves FADH 2.

11. Finally, Enolase makes a water molecule out of 2 bonded hydrogen atoms and a carbon atom along with Biotin to make Phosphoenolpyruvate (PEP).

12. A last enzyme called Pyruvate kinase takes PEP to make ATP, pyruvate, and ADP for the cycle to start all over again.

The 3 Enzyme Complexes of the Krebs Cycle

The Krebs cycle takes place in the mitochondria of cells, specifically in the matrix. The reactions are carried out by a series of enzymes organized into three enzyme complexes: I, II, and III.

Each complex contains one enzyme that starts converting pyruvate to acetyl CoA, another that converts oxaloacetate to malate or Isocitrate, and the third that carries out the cellular respirations needed to produce ATP.

The First Complex

The first complex contains the enzyme pyruvate dehydrogenase that converts Pyruvate to Acetyl-CoA while also converting NADH to NAD+. This reaction releases 2 ATPs through substrate-level phosphorylation. Since it requires an input of energy (ATP), this step is known as substrate-level phosphorylation.

The Second Complex

The second complex is the tricarboxylic acid cycle, but it really should be called the “tetra-carboxylic acid” cycle since there are four carboxylic acids to deal with. This enzyme catalyzes reactions that oxidize acetyl CoA to oxaloacetate, which then becomes malate or Isocitrate. The net result is this step releases 1 NADH and 1 CO2 molecule through substrate-level phosphorylation.

The Third Complex

The third and final complex contains succinyl CoA synthetase and succinate dehydrogenase and the enzymes Q-cytochrome c reductase and cytochrome B (CYTB). Here we begin to see NADH and FADH 2, produced in complexes I and II, used to produce ATP. Q-Cytochrome c reductase transfers electrons from reduced CoQ to the electron acceptor cytochrome c (which is then reduced to form primarily ubiquinol). The following electron transport chain creates the proton gradient that leads to chemiosmotic coupling and ultimately results in ATP synthesis through oxidative phosphorylation.

The electrons carried by NADH are passed down this membrane-bound protein complex until they reach a membrane-bound molecule of coenzyme Q10 known as ubisemiquinone.

Ubisemiquinone picks up two hydrogen atoms from two of NADH, thus forming two hydrogen atoms in the process. Ubisemiquinone then passes them onto a b-type cytochrome enzyme also present in this complex, known as QH2:cyt c oxidoreductase. The enzyme transfers the two hydrogen atoms from ubisemiquinone to the electron acceptor cytochrome c, an iron-containing protein located out of the inner membrane of the mitochondrion. It is reduced by one electron (forming ubiquinol).

Importance of the Krebs Cycle

The Krebs Cycle is important because it releases energy that cells need for cellular activities and reactions. The energy released can be used to produce ATP through chemiosmotic coupling for cell processes such as protein synthesis and motor activities (muscles). For example, Acetyl coenzyme A is made by the Krebs cycle and sent to the electron transport chain, where it releases energy for chemiosmotic coupling, leading to ATP synthesis.

Enzymes control every chemical reaction that takes place in biological organisms. These particular chemicals organize and de-organize molecules into more complex molecules, allowing for different responses to occur depending on what they're doing at the time.

The Krebs cycle enzymes are carefully organized so as many reactions as possible can take place at one time, minimizing the number of steps required and increasing efficiency. However, it also means that this whole process can only occur in a specific part of cells: mitochondria, the cell organelle where cellular respiration takes place.

Krebs Cycle and our Research

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