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Energy transformations in metabolism

The energy needed for various human body functions comes from decomposed nutrient molecules, during a process called metabolism. Metabolism includes two main parts: anabolism (formation, also called biosynthesis) and catabolism (decomposition).

The exact nature of catabolic reactions differs from one organism to another and organisms can be classified according to their sources of energy and carbon:

  • in organotrophs, organic sources are used as a source of energy
  • in the lithotrophes, inorganic substrates are used
  • in the phototrophs, sunlight is used as chemical energy
  • in heterotrophs, organic compounds are used as a source of energy (the compounds are not synthesized by the body but obtained by the diet).

Common basic reactions in catabolism include oxidation-reduction (redox) reactions involving the transfer of electrons from reduced donor molecules, such as organic molecules, water, ammonia, sulfide hydrogen or ferrous ions, into acceptor molecules such as oxygen, nitrates sulfate.

In humans and animals (heterotrophs), oxidation-reduction reactions involve the decomposition of complex organic molecules into simpler molecules, such as carbon dioxide and water. In photosynthetic organisms such as plants and cyanobacteria (phototrophs), these electron transfer reactions do not release energy. These reactions simply help store the energy absorbed by sunlight.

Food energy

In humans, the energy of the body comes from fats, carbohydrates and proteins of food, which makes us heterotrophs. Of the three organic molecules, fat is the most concentrated energy source because it provides more than twice as much energy for a given weight as protein or carbohydrates.

Energy requirements are usually expressed in calories or kilocalories. A kilocalorie (kcal) is the amount of thermal energy needed to raise the temperature of a kilogram of water to a degree Celsius. Fats provide the most energy per mass, at 9 kcal / g, followed by protein and carbohydrate (4 kcal / g) and hydrated carbohydrates (1.3 kcal / g). Lipids are broken down into fatty acids, proteins into amino acids and carbohydrates into glucose. These products then undergo redox reactions.

Basal Metabolic Rate (BMR) is the heat that is removed from the body at rest when the temperature is normal. An average person needs 2,000 to 2,400 calories a day, while a tall man doing heavy work can require up to 6,000 calories a day. Children's energy needs vary considerably according to their age, size and level of activity.

Catabolic processes

Overall, both processes of metabolism, catabolism and anabolism, must occur simultaneously as catabolism provides the energy needed for anabolism. The body uses energy for a variety of functions. It takes energy to perform mechanical work involving the change of location or orientation of a body part or the cell itself. This includes muscle movement. In addition, there is molecular transport and synthesis of biomolecules.

ATP (adenosine triphosphate) is the energy molecule that transfers chemical energy into human cells. In general, the energy required for the synthesis of ATP molecules must be obtained from food molecules. ATP is mainly synthesized in cell mitochondria, with a little extra ATP synthesized in the cytoplasm.

ATP ADP cycle. Adenosine triphosphate (ATP) is an organic chemical that provides energy to cells. intracellular energy transfer. Adenosine diphosphate (ADP) is an organic compound intended for cellular metabolism. Illustration credit: Designua / Shutterstock

ATP ADP cycle. Adenosine triphosphate (ATP) is an organic chemical that provides energy to cells. intracellular energy transfer. Adenosine diphosphate (ADP) is an organic compound intended for cellular metabolism. Illustration credit: Designua / Shutterstock

Catabolism can be divided into three main stages:

  • Digestion – Large organic molecules (proteins, lipids, carbohydrates) are digested into their smaller components (fatty acids, amino acids and glucose, respectively) outside the cell by digestive enzymes, such as glucoside hydrolases for carbohydrates and pepsin for proteins. This occurs in the digestive tract of humans.
  • Energy release – the smaller components are transferred into the cells by active transport proteins and converted into smaller molecules, usually acetyl coenzyme A (acetyl-CoA), which releases the cells. ;energy. In the cytoplasm, glucose is then converted to pyruvate, which causes the synthesis of two molecules of ATP. In humans, these small molecules are transported in the tissues of the digestive system to the circulatory tissues, then distributed throughout the body where they are needed to produce energy.
  • ATP Production – In the citric acid cycle (also called the Kreb or TCA cycle), the acetyl group of CoA is oxidized to water and carbon dioxide. The energy released by it is stored in the ATP by reducing coenzyme adenine dinucleotide (NAD +) to NADH in the electron transport chain. This process is called oxidative phosphorylation and releases carbon dioxide as waste.

The different organic molecules provide different amounts of ATP. Each molecule of fatty acid releases more than 100 ATP molecules and each amino acid molecule releases nearly 40 ATP molecules.

Amino acids can be oxidized to keto acids by removal of the amino group, which is introduced into the urea cycle. It is then the keto acid that enters the cycle of citric acid and contributes to the production of ATP.

When there is no oxygen (anaerobic conditions), less ATP is produced. The glycolysis cycle produces lactate, through the enzyme lactate dehydrogenase, which oxidizes NADH back into NAD + for reuse in glycolysis. Fats can be broken down into glycerol, which goes into glycolysis.

Key biomolecules

Proteins, carbohydrates and lipids are important sources of catabolic reactions, but they are also needed for various other functions in the body. Some are also produced by anabolism, in addition to the DNA. Minerals are also important for metabolic purposes.

The proteins

Proteins are made of amino acids. During the process of protein synthesis, amino acids are linked by long chains called polypeptide chains. These are interconnected by peptide bonds. The polypeptide chains undergo further modification to form proteins.

Some proteins are used to form the structure of cells and tissues, while many others are enzymes that catalyze various chemical reactions in the body. Proteins also play an important role in cell signaling, immune responses, cell adhesion, active transport across membranes and the cell cycle.

Coenzymes are non-proteins (such as minerals or metals) that are involved in many chemical reactions of the body's metabolic pathways. These fall under some basic types of reactions involving the transfer of functional groups.

Coenzymes also help with energy transfer. A central coenzyme is adenosine triphosphate (ATP), the energy motto of the cells. There is only a small amount of ATP in the cells, but it is regenerated continuously. Others include nicotinamide adenine dinucleotide (NADH), a derivative of vitamin B3 that plays the role of hydrogen acceptor.

Hundreds of different types of dehydrogenases remove electrons from their substrates and reduce NAD + to NADH. This reduced form of coenzyme is then a substrate for any of the reductases in the cell that must reduce their substrates. NADH exists in two related forms in the cell, NADH and NADPH. The NAD + / NADH form is more important in catabolic reactions, whereas NADP + / NADPH is used in anabolic reactions.

Carbohydrates

Carbohydrates are the basic source of energy for the body. Carbohydrates are straight chain aldehydes or ketones with hydroxyl groups that may exist as chains or rings.

Carbohydrates are abundant in nature and play many roles in living organisms. They can be converted to glycogen and used as sources of storage energy as structural components (cellulose in plants, chitin in animals) and as a source of direct energy (glucose).

lipids

Lipids are important biochemical substances that have a versatile function in the body. They form the structural part of biological membranes, such as the cell membrane, or are used as a source of energy. Fats are an important group of compounds containing fatty acids and glycerol. The production often takes the form of steroids, such as cholesterol, are another major class of lipids made in cells.

Illustration of lipids and fats. Credit: Naeblys / Shutterstock

Illustration of lipids and fats. Credit: Naeblys / Shutterstock

nucleotides

Nucleotides help in the formation of DNA and RNA. DNA and RNA are long chains of nucleotides essential for the storage and use of genetic information. RNA and DNA also code for protein synthesis. In addition, nucleotides can act as coenzymes in metabolic group transfer reactions.

Cofactors and minerals in metabolism

Organic compounds (proteins, fats and carbohydrates) contain most of the carbon and nitrogen in humans, while most of the oxygen and hydrogen is present in the form of water.
Several minerals and vitamins play a vital role in metabolism. Sodium and potassium are common and abundant. Other important minerals include calcium, phosphorus, iron, chloride ions, copper, zinc, fluorine, iodine and magnesium. Metallic micronutrients are absorbed into organisms by specific carriers.

Cations often act as cofactors that are closely related to a specific protein. The enzymatic cofactors can be modified during catalysis, but the cofactors always return to their initial state once the catalysis is complete.

Thermodynamics of metabolism

Metabolic processes are chemical reactions that often involve heat generation. Cell metabolism associates the spontaneous processes of catabolism with the non spontaneous processes of anabolism. In thermodynamic terms, metabolism maintains equilibrium.

Chemical reactions are classified as either exergonic or enerogonic. This means that a reaction can release useful energy at work (exergonic reaction) or require energy (an energetic reaction). ATP production during catabolism is therefore exergonic, whereas anabolism is an energetic response.

Metabolic control

Metabolic pathways are complex and interdependent. When environments change, metabolism reactions must be precisely regulated to maintain a constant set of conditions in cells – a condition called homeostasis. Control of metabolic pathways also allows organisms to respond to signals and interact with their environment.

Levels of metabolic regulation

There are several levels of metabolic regulation. For intrinsic regulation of metabolic pathways, reactions self-regulate to respond to changes in substrate or product levels. For example, a decrease in the amount of product may increase the metabolic pathway. This is called a feedback mechanism.

Extrinsic control involves a cell in a multicellular organism that alters its metabolism in response to signals from other cells. Signals approach pathways via soluble messengers, such as hormones and growth factors. For example, the hormone insulin pancreatic beta cells is produced in response to the increase in blood sugar. The binding of the hormone to the insulin receptors on the cells then activates a cascade of protein kinases that causes the cells to absorb the glucose and convert it into storage molecules, such as fatty acids and the glycogen.

Regulation of carbohydrate metabolism

Glucose homeostasis is a complex interaction of metabolic pathways, but it is vital for living organisms. These processes increase or decrease blood sugar, but they work together to maintain optimal levels.

Glucose is derived from carbohydrates taken from the diet. Carbohydrates are digested into simple sugars: glucose, fructose and galactose. These sugars are absorbed in the intestine and transported to the liver through the portal vein. Then the liver converts fructose and galactose into glucose. The increase in glucose levels in the blood stimulates the release of insulin by islet beta cells in the pancreas.

Insulin is the only hormone that reduces blood glucose levels, by activating glucose transport mechanisms and metabolic pathways using glucose in different tissues of the body. Thus, insulin regulates down the glucose formation pathways.

Insulin and glucose. Beta cells (in the pancreas) release insulin into the blood vessel. Insulin stimulates the uptake of glucose into skeletal muscle. Close up of pancreas and islets of Langerhans. Image credit: Designua / Shutterstock

Insulin and glucose. Beta cells (in the pancreas) release insulin into the blood vessel. Insulin stimulates the uptake of glucose into skeletal muscle. Close up of pancreas and islets of Langerhans. Image credit: Designua / Shutterstock

Insulin stimulates the uptake of glucose (by muscles and adipose tissue), glycolysis, glycogenesis (formation of glycogen from free glucose) and protein synthesis. Conversely, insulin inhibits gluconeogenesis (glucose formation from fatty acids, etc.), lipolysis (fatty acid degradation), proteolysis (protein degradation) and ketogenesis (body formation). ketone).

Metabolic disorders and manipulation

Metabolic pathways are complex and often interdependent. Any changes in the pathways can lead to complex disorders. For example, the imbalance of glucose homeostasis and carbohydrate metabolism is related to diabetes. This makes the study of metabolic pathways and their important handling in clinical diagnosis and management.

Investigations into metabolic pathways and disorders

Evaluation of the end products of the pathways is one of the most useful tools for studying unbalanced metabolic pathways. For example, in diabetes mellitus, the hormonal insulin that maintains normal blood sugar levels is insufficient, and the evaluation of fasting (after 8 to 10 hours without food) and post-prandial treatment (2 hours after taking the meal) help diagnosis.

The use of radioactive tracers or metabolomics is another method of studying metabolic pathways in research (but not clinical care). Radioactive tracers can help define precursor paths to finished products by identifying intermediates and radioactively labeled products. Once the labeled chemicals are evaluated, the enzymes that catalyze these chemical reactions can be purified and their kinetics and responses to the inhibitors can be investigated. Metabolomic studies can provide information on the structure and function of simple metabolic pathways. However, these studies may be insufficient when they are applied to more complex systems, such as the metabolism of a complete cell. Indeed, metabolic networks within the cell contain thousands of different enzymes and complex networks. The genomes reveal that there are nearly 45,000 genes that can code for enzymes and other cofactors within the metabolic pathways.

Handling metabolic pathways

Since the advent of genomic studies, the manipulation of gene expression from proteomics and microarray studies has been developed. Many innate metabolic disorders have been treated by gene therapy and manipulation of genes encoding enzymes and defective proteins in metabolic pathways.

With the help of genetics, a model of human metabolism has now been developed that will guide future drug discovery and biochemical research. These models are now used in network analysis to classify human diseases into groups sharing common proteins or metabolites.

Metabolic engineering is the targeted and targeted alteration of metabolic pathways present in the body. This helps to understand and use the cellular pathways for chemical transformation, energy transduction and supramolecular assembly. Metabolic engineering relies on the principles of chemical engineering, computer science, biochemistry and molecular biology to design and analyze pathways of penetration.

Metabolic engineering uses organisms such as yeasts, plants or genetically modified bacteria to make them more useful in biotechnology and assist in the production of drugs such as antibiotics or industrial chemicals 1,3-propanediol and shikimic acid. These changes aim to reduce the amount of energy used to make the product, increase yields and reduce waste generation.

Evolution

Metabolic pathways include several long and complex molecular and chemical reactions that have been conserved during evolution, so that even the simplest organisms share some common metabolic pathways with complex organisms such as l? man.

The retention of these old pathways may result from the fact that these reactions are an optimal solution to their particular metabolic problems. For example, glycolysis and the cycle of citric acid produce their finished products very efficiently and in a minimal number of steps. This economy and this optimal situation have led to the evolution of these reactions over time.

Evolution of the cycle of citric acid

The evolutionary origin of the citric acid cycle has long been a model case in understanding the origin and evolution of metabolic pathways. Although the chemical stages of the cycle remain intact throughout nature, various organisms make a variety of uses. In some cases, organizations use only selected parts of the cycle.

More than one hypothesis has been proposed to explain the evolution of metabolic pathways. These include the sequential addition of new enzymes to much shorter anterior pathways, as well as the recruitment of pre-existing enzymes and their assembly into a new pathway.

Genomic studies have shown that enzymes in a pathway probably have a common origin, suggesting that many pathways have evolved gradually. During track development, new functions were created from pre-existing track stages.

Another hypothesis comes from studies that trace the evolution of protein structures in metabolic networks. This shows that enzymes are recruited ubiquitously. These recruitment processes result in an evolutionary enzymatic mosaic.

It is also possible that some parts of the metabolism exist as "modules" that can be reused in different pathways and perform similar functions on different molecules. In addition, some functions and parts of the pathways that are not essential to survival are lost over time.

History

Metabolism and metabolic pathways have been studied over several centuries and have moved from early studies to the study of whole animals, to the examination of individual metabolic reactions in biochemistry and molecular biology modern.

Early metabolic studies

Metabolic studies were carried out as early as the 13th century by Ibn al-Nafis (1213-1288), who stated that "the body and its parts are in a state of continual dissolution and nourishment, so that". they inevitably undergo a permanent change ".

The recorded and more sophisticated studies of metabolism began in the last decades of the sixteenth century. It was at this time that direct observation was supplemented by instrumentation allowing quantification and, hence, verification in the sciences, especially biological systems. In medicine, progress depends on the application of the exact sciences of chemistry, mathematics and physics to the study of function.

Santorio Sanctorius (1561-1636) contributed to metabolic studies by exploring sweating. His efforts over the years of experimentation led to studies on metabolic balance. The first controlled experiments on human metabolism were published by Santorio Santorio in 1614 in his book "Ars de statica medecina". In the course of his experiments, he weighed himself before and after eating, sleeping, working, having sex, lying on a fast, drunk and excreted. He found that most of the food he absorbed was lost due to what he called "insensitive sweating."

The first studies on metabolism were conducted on live animals or human volunteers. The mechanisms of these metabolic processes had not yet been identified and it was thought that a vital force animated the living tissues.

Metabolic studies of the 19th century

It was in the 19th century, when Louis Pasteur experimented with the fermentation of sugar into alcohol in yeast that he noticed that fermentation was catalyzed by substances contained in the yeast cells that he called "ferments".

This discovery, together with the publication by Friedrich Wöhler in 1828 of the chemical synthesis of urea, laid the foundation for the study of organic compounds and chemical reactions present in the cells constituting the metabolic pathways.

Metabolic studies of the 20th century

At the beginning of the 20th century, Eduard Buchner advanced knowledge by discovering enzymes. He discovered that the study of chemical reactions of metabolism was a different branch of the biological study of cells and began to understand the basics of biochemistry. The early 20th century saw the rapid development of biochemical studies.

The most notable discoveries were the discovery of the cycle of citric acid by Hans Krebs, who greatly contributed to the study of metabolism. He discovered the cycle of urea and later, working with Hans Kornberg, the citric acid cycle and the glyoxylate cycle.

Metabolic studies in progress

Metabolism is now being studied using molecular biotechnology techniques and genomics. Instruments such as chromatography, X-ray diffraction, NMR spectroscopy, radioisotope labeling, electron microscopy and molecular dynamics simulations are commonly used. These techniques allowed the discovery and detailed analysis of metabolic pathways and the genetic basis of metabolic disorders.

Studies over the last two centuries have also advanced understanding of drug metabolism and xenobiotic metabolism.

sources

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