CATABOLISM: CATABOLIC FUNCTIONS AND PROCESSES - BIOLOGY - 2024

The catabolism encompasses all degradation reactions of substances in the body. In addition to "breaking down" the components of biomolecules into their smallest units, catabolic reactions produce energy, mainly in the form of ATP.

The catabolic pathways are responsible for degrading the molecules that come from food: carbohydrates, proteins and lipids. During the process, the chemical energy contained in the bonds is released to be used in cellular activities that require it.

Source: By EsquemaCatabolismo.svg: myself; correction of small mistakes: Basquetteurderivative work: Gustavocarra (EsquemaCatabolismo.svg), via Wikimedia Commons

Some examples of well-known catabolic pathways are: the Krebs cycle, beta oxidation of fatty acids, glycolysis, and oxidative phosphorylation.

The simple molecules produced by catabolism are used by the cell to build the necessary elements, also using the energy provided by the same process. This synthesis pathway is the antagonist of catabolism and is called anabolism.

The metabolism of an organism encompasses both synthesis and degradation reactions, which occur simultaneously and in a controlled manner within the cell.

Features

Catabolism's main objective is to oxidize the nutrients that the body uses as "fuel", called carbohydrates, proteins and fats. The degradation of these biomolecules generates energy and waste products, mainly carbon dioxide and water.

A series of enzymes participate in catabolism, which are proteins responsible for accelerating the speed of chemical reactions that occur in the cell.

Fuel substances are the food we consume daily. Our diet is made up of proteins, carbohydrates and fats that are broken down by catabolic pathways. The body preferentially uses fats and carbohydrates, although in situations of scarcity it can resort to the breakdown of proteins.

The energy extracted by catabolism is contained in the chemical bonds of the mentioned biomolecules.

When we are consuming any food, we chew it to make it easier to digest. This process is analogous to catabolism, where the body is in charge of “digesting” the particles at the microscopic level so that they are used by the synthesis or anabolic routes.

Catabolic processes

The catabolic pathways or pathways include all the degradation processes of substances. We can distinguish three stages in the process:

- The different biomolecules found in the cell (carbohydrates, fats and proteins) are degraded in the fundamental units that constitute them (sugars, fatty acids and amino acids, respectively).

- The products of stage I pass to simpler constituents, which converge in a common intermediate called acetyl-CoA.

- Finally, this compound enters the Krebs cycle, where it continues its oxidation until it yields molecules of carbon dioxide and water - the final molecules obtained in any catabolic reaction.

Among the most prominent are the urea cycle, the Krebs cycle, glycolysis, oxidative phosphorylation and beta oxidation of fatty acids. Below we will describe each of the mentioned routes:

The urea cycle

The urea cycle is a catabolic pathway that occurs in mitochondria and in the cytosol of liver cells. It is responsible for the processing of protein derivatives and the final product of it is urea.

The cycle begins with the entry of the first amino group from the matrix of the mitochondria, although it can also enter the liver through the intestine.

The first reaction step involves ATP, bicarbonate ions (HCO ₃ ^-) and ammonium (NH ₄ ⁺) carbomoyl phosphate, ADP and P _i. The second step consists of the union of carbomoyl phosphate and ornithine to yield a molecule of citrulline and P _i. These reactions occur in the mitochondrial matrix.

The cycle continues in the cytosol, where citrulline and aspartate condense together with ATP to generate argininosuccinate, AMP and PP _i. Argininosuccinate passes into arginine and fumarate. The amino acid arginine combines with water to give ornithine and finally urea.

This cycle is interconnected with the Krebs cycle because the fumarate metabolite participates in both metabolic pathways. However, each cycle acts independently.

The clinical pathologies related to this pathway prevent the patient from eating a diet rich in protein.

The Krebs cycle or citric acid cycle

The Krebs cycle is a pathway that participates in the cellular respiration of all organisms. Spatially, it occurs in the mitochondria of eukaryotic organisms.

The precursor to the cycle is a molecule called acetyl coenzyme A, which condenses with an oxaloacetate molecule. This union generates a six-carbon compound. In each revolution, the cycle yields two molecules of carbon dioxide and one molecule of oxaloacetate.

The cycle begins with an isomerization reaction catalyzed by aconitase, where the citrate passes into cis-aconitate and water. Similarly, aconitase catalyzes the passage of cis-aconitate into isocitrate.

Isocitrate is oxidized to oxalosuccinate by isocitrate dehydrogenase. This molecule is decarboxylated into alpha-ketoglutarate by the same enzyme, isocitrate dehydrogenase. Alpha-ketoglutarate is converted to succinyl-CoA by the action of alpha-ketoglutarate dehydrogenase.

Succinyl-CoA becomes succinate, which is oxidized to fumarate by succinate dehydrogenase. Successively the fumarate becomes l-malate and finally the l-malate becomes oxaloacetate.

The cycle can be summarized in the following equation: Acetyl-CoA + 3 NAD ⁺ + FAD + GDP + Pi + 2 H ₂ O → CoA-SH + 3 (NADH + H +) + FADH ₂ + GTP + 2 CO ₂.

Glycolysis

Glycolysis, also called glycolysis, is a crucial pathway that is present in virtually all living organisms, from microscopic bacteria to large mammals. The route consists of 10 enzymatic reactions that break down glucose to pyruvic acid.

The process begins with the phosphorylation of the glucose molecule by the enzyme hexokinase. The idea of ​​this step is to "activate" the glucose and trap it inside the cell, since glucose-6-phosphate does not have a transporter through which it can escape.

Glucose-6-phosphate isomerase takes glucose-6-phosphate and rearranges it into its fructose-6-phosphate isomer. The third step is catalyzed by phosphofructokinase and the product is fructose-1,6-bisphosphate.

Then, the aldolase cleaves the above compound into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. There is an equilibrium between these two compounds catalyzed by triose phosphate isomerase.

The enzyme glyceraldehyde-3-phosphate dehydrogenase produces 1,3-bisphosphoglycerate which is converted to 3-phosphoglycerate in the next step by phosphoglycerate kinase. Phosphoglycerate mutase changes the position of the carbon and yields 2-phosphoglycerate.

Eolase takes the latter metabolite and converts it to phosphoenolpyruvate. The last step in the pathway is catalyzed by pyruvate kinase and the end product is pyruvate.

Oxidative phosphorylation

Oxidative phosphorylation is a process of ATP formation thanks to the transfer of electrons from NADH or FADH ₂ to oxygen and constitutes the last step in cellular respiration processes. It occurs in the mitochondria and is the main source of ATP molecules in aerobic respiration organisms.

Its importance is undeniable, since 26 out of 30 ATP molecules that are generated as a product of the complete oxidation of glucose to water and carbon dioxide occur by oxidative phosphorylation.

Conceptually, oxidative phosphorylation couples the oxidation and synthesis of ATP with a flow of protons through the membrane system.

Thus, NADH or FADH ₂ generated in different routes, call it glycolysis or oxidation of fatty acids, is used to reduce oxygen and the free energy generated in the process is used for the synthesis of ATP.

β-oxidation of fatty acids

Β-oxidation is a set of reactions that allow the oxidation of fatty acids to produce high amounts of energy.

The process involves the periodic release of regions of the two-carbon fatty acid by reaction until the fatty acid is completely degraded. The end product is acetyl-CoA molecules that can enter the Krebs cycle to be fully oxidized.

Before oxidation, the fatty acid must be activated, where it binds to coenzyme A. The carnitine transporter is responsible for translocating the molecules to the matrix of the mitochondria.

After these previous steps, the β-oxidation itself begins with the processes of oxidation, hydration, oxidation by NAD ⁺ and thiolysis.

Regulation of catabolism

There must be a series of processes that regulate the different enzymatic reactions, since these cannot work all the time at their maximum speed. Thus, metabolic pathways are regulated by a number of factors including hormones, neuronal controls, substrate availability, and enzymatic modification.

In every route there must be at least one irreversible reaction (that is, it occurs in only one direction) and that directs the speed of the entire route. This allows the reactions to be working at the speed required by the cell and prevents the synthesis and degradation pathways from working at the same time.

Hormones are particularly important substances that act as chemical messengers. These are synthesized in the various endocrine glands and released into the bloodstream to act. Some examples are:

Cortisol

Cortisol works by slowing down the synthesis processes and increasing the catabolic pathways in the muscle. This effect occurs by the release of amino acids into the bloodstream.

Insulin

In contrast, there are hormones that have the opposite effect and decrease catabolism. Insulin is responsible for increasing protein synthesis and at the same time decreases their catabolism. In this event, proteolysis increases, which facilitates the output of amino acids to the muscle.

Differences with anabolism

Anabolism and catabolism are antagonistic processes that comprise the totality of metabolic reactions that occur in an organism.

Both processes require multiple chemical reactions catalyzed by enzymes and are under strict hormonal control capable of triggering or slowing down certain reactions. However, they differ in the following fundamental aspects:

Synthesis and degradation of molecules

Anabolism comprises the synthesis reactions while catabolism is responsible for the degradation of molecules. Although these processes are reversed, they are connected in the delicate balance of metabolism.

Anabolism is said to be a divergent process, taking simple compounds and transforming them into larger compounds. Contrary to catabolism, which is classified as a convergent process, due to the obtaining of small molecules such as carbon dioxide, ammonia and water, from large molecules.

The different catabolic pathways take the macromolecules that make up food and reduce them to their smallest constituents. Anabolic pathways, meanwhile, are capable of taking these units and building more elaborate molecules again.

In other words, the body has to "change the configuration" of the elements that make up food so that they are used in the processes it requires.

The process is analogous to the popular Lego game, where the main constituents can form different structures with a wide variety of spatial arrangements.

Use of energy

Catabolism is responsible for extracting the energy contained in the chemical bonds of food, therefore its main objective is the generation of energy. This degradation occurs, in most cases, by oxidative reactions.

However, it is not surprising that catabolic pathways require adding energy in their initial steps, as we saw in the glycolytic pathway, which requires the inversion of ATP molecules.

On the other hand, anabolism is responsible for adding the free energy produced in catabolism to achieve the assembly of the compounds of interest. Both anabolism and catabolism occur constantly and simultaneously in the cell.

Generally, ATP is the molecule used to transfer energy. This can diffuse to the areas where it is required and when it hydrolyzes the chemical energy contained in the molecule is released. Similarly, energy can be transported as hydrogen atoms or electrons.

These molecules are called coenzymes and include NADP, NADPH, and FMNH ₂. They act through reduction reactions. Furthermore, they can transfer the reducing capacity into ATP.

References

1. Chan, YK, Ng, KP, & Sim, DSM (Eds.). (2015). Pharmacological Basis of Acute Care. Springer International Publishing.
2. Curtis, H., & Barnes, NS (1994). Invitation to biology. Macmillan.
3. Lodish, H., Berk, A., Darnell, JE, Kaiser, CA, Krieger, M., Scott, MP,… & Matsudaira, P. (2008). Molecular cell biology. Macmillan.
4. Ronzio, RA (2003). The encyclopedia of nutrition and good health. Infobase Publishing.
5. Voet, D., Voet, J., & Pratt, CW (2007). Foundations of Biochemistry: Life at the molecular level. Panamerican Medical Ed.