What is the Krebs cycle and why is it so important for life? It is a metabolic route, in which a series of chemical reactions occur in the matrix of the mitochondria of aerobic cells, so that they can obtain the energy they need from the nutrients consumed.
In this article we will explore in a simple and clear way how this metabolic pathway works that allows aerobic cells to obtain energy from nutrients. Furthermore, we will see the central role of this cycle in metabolic catabolism and anabolism, analyzing the routes that converge in it.
If you want to learn what the Krebs cycle is, its reactions, products and biological relevance , immerse yourself with us in this article about one of the most studied routes of cellular metabolism.
What is the Krebs cycle and where does it occur?
It is a metabolic route , which means that it is a succession or series of chemical reactions that occurs inside living beings, specifically aerobic cells , which was discovered by the German biochemist Hans Krebs in 1937 , of whom adopted his name. The Krebs cycle is also known as the tricarboxylic acid cycle or citric acid cycle , and today its relevance and central role in the metabolism of carbohydrates, lipids and proteins is well known .
It consists of a series of chemical reactions that occur in the matrix of mitochondria , which are cellular organelles whose main function is the production of chemical energy, where acetyl-CoA from carbohydrates, lipids and proteins is oxidized into carbon dioxide and water, releasing energy in the form of ATP and NADH. This set of cyclic reactions is considered a catabolic-type cycle , but it also provides precursors for the biosynthesis of other molecules, such as amino acids and fatty acids.
Krebs cycle reactions
In this cycle, the acetyl groups from the pyruvate resulting, for example, from glycolysis, are oxidized and GTP, NADH, FADH2 and CO2 molecules are produced. Eight key steps can be distinguished in this cycle, although some of them can be broken down into more than one chemical reaction. Let’s see what those eight steps of the Krebs cycle are:
- Citrate formation: The first reaction is the condensation of acetyl-CoA with oxaloacetate to form citrate and release coenzyme A. This reaction is catalyzed by the enzyme citrate synthase.
- Formation of isocitrate: the second reaction is the isomerization of citrate to isocitrate, through the elimination and addition of a water molecule. This reaction is catalyzed by the enzyme aconitase.
- Oxidation of isocitrate to alpha-ketoglutarate: The third reaction is the oxidation of isocitrate to alpha-ketoglutarate and CO2, with the simultaneous reduction of NAD+ to NADH. This reaction is catalyzed by the enzyme isocitrate dehydrogenase.
- Oxidation of alpha-ketoglutarate to succinyl-CoA and CO2: The fourth reaction is the oxidation of alpha-ketoglutarate to succinyl-CoA and CO2, with the simultaneous reduction of NAD+ to NADH. This reaction is catalyzed by the enzyme complex alpha-ketoglutarate dehydrogenase.
- Conversion of succinyl-CoA to succinate: The fifth reaction is the transfer of the succinyl group from succinyl-CoA to GDP to form GTP and succinate, with the release of coenzyme A. This reaction is catalyzed by the enzyme succinyl-CoA synthetase.
- Oxidation of succinate to fumarate: The sixth reaction is the oxidation of succinate to fumarate, with the simultaneous reduction of FAD to FADH2. This reaction is catalyzed by the enzyme succinate dehydrogenase, which is associated with the inner mitochondrial membrane.
- Hydration of fumarate to malate: The seventh reaction is the hydration of fumarate to malate, through the addition of a water molecule. This reaction is catalyzed by the enzyme fumarase.
- Oxidation of malate to oxaloacetate: The eighth and final reaction is the oxidation of malate to oxaloacetate, with the simultaneous reduction of NAD+ to NADH. This reaction is catalyzed by the enzyme malate dehydrogenase. In this way, the oxaloacetate is regenerated, which will participate again in the first reaction of the cycle.
- Following this pattern, the Krebs cycle is repeated twice for each molecule of glucose that enters glycolysis , since two molecules of acetyl-CoA are generated for each molecule of pyruvate. The net balance of the Krebs cycle for each molecule of acetyl-CoA is: 1 ATP (or GTP), 3 NADH, 1 FADH2 and 2 CO2.
Products of the Krebs cycle
The products of the Krebs cycle are molecules that are formed from the oxidation of acetyl-CoA , which comes from the degradation of carbohydrates, fats and proteins. Two molecules of CO2, one molecule of GTP (equivalent to one ATP), three molecules of NADH and one molecule of FADH2 are generated for each turn of the cycle. These products are important for cellular metabolism, since GTP is used as an energy source and NADH and FADH2 are used to fuel the cellular respiratory chain and thus produce more ATP.
So for each complete turn of the Krebs cycle we obtain:
- 2 CO2
- 1 GTP
- 3 NADH
- 1 FADH2
Pathways that converge in the Krebs cycle
Since it was discovered, the Krebs cycle has been the subject of intense scientific study and research. And the more we know about this cyclic metabolic pathway, the greater the interest it has generated in the scientific community.
This cycle is considered a catabolic route , that is, whose task is to go from complex molecules to simpler ones to produce chemical energy and reducing power . But it is also known that its importance is not limited to energy production, since it is a central metabolic route that connects different pathways of energy production and consumption in cells.
As we have already seen, in this cycle, acetyl-CoA is completely oxidized to carbon dioxide and water. The interesting thing is that this acetyl-CoA can come from different sources, such as glycolysis, fatty acid oxidation or collagen production, making the Krebs cycle a meeting point in the catabolism of carbohydrates, lipids and proteins .
In addition, the Krebs cycle also generates intermediates that can be used in anabolic pathways, which are those that start from relatively simple molecules to convert them into other more complex molecules.
Some examples are the synthesis of amino acids, nucleotides or lipids. Therefore, the Krebs cycle is a point of convergence and divergence of multiple metabolic processes, both catabolic and anabolic, that regulate energy balance and cellular biosynthesis .