Metabolism (, from metabolē, "change") refers to the set of life-sustaining chemical reactions that occur within . The three main functions of metabolism are: converting the energy in food into a usable form for cellular processes; converting food to building blocks of , , , and some ; and eliminating . These enzyme-catalyzed reactions allow organisms to grow, reproduce, maintain their structures, and respond to their environments. The word metabolism can also refer to all chemical reactions that occur in living organisms, including digestion and the transportation of substances into and between different cells. In a broader sense, the set of reactions occurring within the cells is called intermediary (or intermediate) metabolism.
Metabolic reactions may be categorized as catabolic—the breaking down of compounds (for example, of glucose to pyruvate by cellular respiration); or anabolic—the building up (biosynthesis) of compounds (such as proteins, carbohydrates, lipids, and nucleic acids). Usually, catabolism releases energy, and anabolism consumes energy.
The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed through a series of steps into another chemical, each step being facilitated by a specific enzyme. Enzymes are crucial to metabolism because they allow organisms to drive desirable reactions that require energy and will not occur by themselves, by coupling them to spontaneous reactions that release energy. Enzymes act as Catalysis—they allow a reaction to proceed more rapidly—and they also allow the regulation of the rate of a metabolic reaction, for example in response to changes in the cell's environment or to cell signaling from other cells.
The metabolic system of a particular organism determines which substances it will find nutrition and which . For example, some use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals. The basal metabolic rate of an organism is the measure of the amount of energy consumed by all of these chemical reactions.
A striking feature of metabolism is the similarity of the basic metabolic pathways among vastly different species. For example, the set of that are best known as the intermediates in the citric acid cycle are present in all known organisms, being found in species as diverse as the unicellular bacterium Escherichia coli and huge multicellular organisms like . These similarities in metabolic pathways are likely due to their early appearance in evolutionary history, and their retention is likely due to their efficacy. In various diseases, such as type II diabetes, metabolic syndrome, and cancer, normal metabolism is disrupted. The metabolism of cancer cells is also different from the metabolism of normal cells, and these differences can be used to find targets for therapeutic intervention in cancer.
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One central coenzyme is adenosine triphosphate (ATP), the energy currency of cells. This nucleotide is used to transfer chemical energy between different chemical reactions. There is only a small amount of ATP in cells, but as it is continuously regenerated, the human body can use about its own weight in ATP per day. ATP acts as a bridge between catabolism and anabolism. Catabolism breaks down molecules, and anabolism puts them together. Catabolic reactions generate ATP, and anabolic reactions consume it. It also serves as a carrier of phosphate groups in phosphorylation reactions.
A vitamin is an organic compound needed in small quantities that cannot be made in cells. In human nutrition, most vitamins function as coenzymes after modification; for example, all water-soluble vitamins are phosphorylated or are coupled to nucleotides when they are used in cells. Nicotinamide adenine dinucleotide (NAD+), a derivative of vitamin B3 (niacin), is an important coenzyme that acts as a hydrogen acceptor. Hundreds of separate types of remove electrons from their substrates and redox NAD+ into NADH. This reduced form of the coenzyme is then a substrate for any of the in the cell that need to transfer hydrogen atoms to their substrates. Nicotinamide adenine dinucleotide exists in two related forms in the cell, NADH and NADPH. The NAD+/NADH form is more important in catabolic reactions, while NADP+/NADPH is used in anabolic reactions.
The abundant inorganic elements act as . The most important ions are sodium, potassium, calcium, magnesium, chloride, phosphate and the organic ion bicarbonate. The maintenance of precise across maintains osmotic pressure and pH. Ions are also critical for nerve and muscle function, as in these tissues are produced by the exchange of electrolytes between the extracellular fluid and the cell's fluid, the cytosol. Electrolytes enter and leave cells through proteins in the cell membrane called . For example, muscle contraction depends upon the movement of calcium, sodium and potassium through ion channels in the cell membrane and .
are usually present as in organisms, with zinc and iron being most abundant of those.
+Classification of organisms based on their metabolism (2025). 9783827371874, Pearson Studium. ISBN 9783827371874 |
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The most common set of catabolic reactions in animals can be separated into three main stages. In the first stage, large organic molecules, such as , or , are digested into their smaller components outside cells. Next, these smaller molecules are taken up by cells and converted to smaller molecules, usually acetyl-CoA (acetyl-CoA), which releases some energy. Finally, the acetyl group on acetyl-CoA is oxidized to water and carbon dioxide in the citric acid cycle and electron transport chain, releasing more energy while reducing the coenzyme nicotinamide adenine dinucleotide (NAD+) into NADH.
Microbes simply secrete digestive enzymes into their surroundings, while animals only secrete these enzymes from specialized cells in their guts, including the stomach and pancreas, and in . The amino acids or sugars released by these extracellular enzymes are then pumped into cells by active transport proteins.
Fats are catabolized by hydrolysis to free fatty acids and glycerol. The glycerol enters glycolysis and the fatty acids are broken down by beta oxidation to release acetyl-CoA, which then is fed into the citric acid cycle. Fatty acids release more energy upon oxidation than carbohydrates. Steroids are also broken down by some bacteria in a process similar to beta oxidation, and this breakdown process involves the release of significant amounts of acetyl-CoA, propionyl-CoA, and pyruvate, which can all be used by the cell for energy. M. tuberculosis can also grow on the lipid cholesterol as a sole source of carbon, and genes involved in the cholesterol-use pathway(s) have been validated as important during various stages of the infection lifecycle of M. tuberculosis.
are either used to synthesize proteins and other biomolecules, or oxidized to urea and carbon dioxide to produce energy. The oxidation pathway starts with the removal of the amino group by a transaminase. The amino group is fed into the urea cycle, leaving a deaminated carbon skeleton in the form of a keto acid. Several of these keto acids are intermediates in the citric acid cycle, for example α-ketoglutarate formed by deamination of glutamate. The glucogenic amino acids can also be converted into glucose, through gluconeogenesis.
In many organisms, the capture of solar energy is similar in principle to oxidative phosphorylation, as it involves the storage of energy as a proton concentration gradient. This proton motive force then drives ATP synthesis. The electrons needed to drive this electron transport chain come from light-gathering proteins called photosynthetic reaction centres. Reaction centers are classified into two types depending on the nature of photosynthetic pigment present, with most photosynthetic bacteria only having one type, while plants and cyanobacteria have two.
In plants, algae, and cyanobacteria, photosystem uses light energy to remove electrons from water, releasing oxygen as a waste product. The electrons then flow to the cytochrome b6f complex, which uses their energy to pump protons across the thylakoid membrane in the chloroplast. These protons move back through the membrane as they drive the ATP synthase, as before. The electrons then flow through photosystem and can then be used to reduce the coenzyme NADP+. This coenzyme can enter the Calvin cycle or be recycled for further ATP generation.
Anabolism in organisms can be different according to the source of constructed molecules in their cells. such as plants can construct the complex organic molecules in their cells such as polysaccharides and proteins from simple molecules like carbon dioxide and water. , on the other hand, require a source of more complex substances, such as monosaccharides and amino acids, to produce these complex molecules. Organisms can be further classified by ultimate source of their energy: photoautotrophs and photoheterotrophs obtain energy from light, whereas chemoautotrophs and chemoheterotrophs obtain energy from oxidation reactions.
In photosynthetic the mechanisms of carbon fixation are more diverse. Here, carbon dioxide can be fixed by the Calvin–Benson cycle, a reversed citric acid cycle, or the carboxylation of acetyl-CoA. Prokaryotic Chemotroph also fix CO2 through the Calvin–Benson cycle, but use energy from inorganic compounds to drive the reaction.
Although fat is a common way of storing energy, in such as humans the in these stores cannot be converted to glucose through gluconeogenesis as these organisms cannot convert acetyl-CoA into pyruvate; plants do, but animals do not, have the necessary enzymatic machinery. As a result, after long-term starvation, vertebrates need to produce Ketone body from fatty acids to replace glucose in tissues such as the brain that cannot metabolize fatty acids. In other organisms such as plants and bacteria, this metabolic problem is solved using the glyoxylate cycle, which bypasses the decarboxylation step in the citric acid cycle and allows the transformation of acetyl-CoA to oxaloacetate, where it can be used for the production of glucose. Other than fat, glucose is stored in most tissues, as an energy resource available within the tissue through glycogenesis which was usually being used to maintained glucose level in blood.
Polysaccharides and are made by the sequential addition of monosaccharides by glycosyltransferase from a reactive sugar-phosphate donor such as uridine diphosphate glucose (UDP-Glc) to an acceptor hydroxyl group on the growing polysaccharide. As any of the hydroxyl groups on the ring of the substrate can be acceptors, the polysaccharides produced can have straight or branched structures. The polysaccharides produced can have structural or metabolic functions themselves, or be transferred to lipids and proteins by the enzymes oligosaccharyltransferases.
and terpenoid are a large class of lipids that include the and form the largest class of plant . These compounds are made by the assembly and modification of isoprene units donated from the reactive precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate. These precursors can be made in different ways. In animals and archaea, the mevalonate pathway produces these compounds from acetyl-CoA, while in plants and bacteria the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates. One important reaction that uses these activated isoprene donors is sterol biosynthesis. Here, the isoprene units are joined to make squalene and then folded up and formed into a set of rings to make lanosterol. Lanosterol can then be converted into other sterols such as cholesterol and ergosterol.
Amino acids are made into proteins by being joined in a chain of . Each different protein has a unique sequence of amino acid residues: this is its primary structure. Just as the letters of the alphabet can be combined to form an almost endless variety of words, amino acids can be linked in varying sequences to form a huge variety of proteins. Proteins are made from amino acids that have been activated by attachment to a transfer RNA molecule through an ester bond. This aminoacyl-tRNA precursor is produced in an ATP-dependent reaction carried out by an aminoacyl tRNA synthetase. This aminoacyl-tRNA is then a substrate for the ribosome, which joins the amino acid onto the elongating protein chain, using the sequence information in a messenger RNA.
A related problem for is oxidative stress. Here, processes including oxidative phosphorylation and the formation of during protein folding produce reactive oxygen species such as hydrogen peroxide. These damaging oxidants are removed by antioxidant metabolites such as glutathione and enzymes such as and .
There are multiple levels of metabolic regulation. In intrinsic regulation, the metabolic pathway self-regulates to respond to changes in the levels of substrates or products; for example, a decrease in the amount of product can increase the flux through the pathway to compensate. This type of regulation often involves allosteric regulation of the activities of multiple enzymes in the pathway. Extrinsic control involves a cell in a multicellular organism changing its metabolism in response to signals from other cells. These signals are usually in the form of water-soluble messengers such as and and are detected by specific receptors on the cell surface. These signals are then transmitted inside the cell by second messenger systems that often involved the phosphorylation of proteins.
A very well understood example of extrinsic control is the regulation of glucose metabolism by the hormone insulin. Insulin is produced in response to rises in blood sugar. Binding of the hormone to on cells then activates a cascade of that cause the cells to take up glucose and convert it into storage molecules such as fatty acids and glycogen. The metabolism of glycogen is controlled by activity of phosphorylase, the enzyme that breaks down glycogen, and glycogen synthase, the enzyme that makes it. These enzymes are regulated in a reciprocal fashion, with phosphorylation inhibiting glycogen synthase, but activating phosphorylase. Insulin causes glycogen synthesis by activating phosphatase and producing a decrease in the phosphorylation of these enzymes.
Many models have been proposed to describe the mechanisms by which novel metabolic pathways evolve. These include the sequential addition of novel enzymes to a short ancestral pathway, the duplication and then divergence of entire pathways as well as the recruitment of pre-existing enzymes and their assembly into a novel reaction pathway. The relative importance of these mechanisms is unclear, but genomic studies have shown that enzymes in a pathway are likely to have a shared ancestry, suggesting that many pathways have evolved in a step-by-step fashion with novel functions created from pre-existing steps in the pathway. An alternative model comes from studies that trace the evolution of proteins' structures in metabolic networks, this has suggested that enzymes are pervasively recruited, borrowing enzymes to perform similar functions in different metabolic pathways (evident in the MANET database) These recruitment processes result in an evolutionary enzymatic mosaic. A third possibility is that some parts of metabolism might exist as "modules" that can be reused in different pathways and perform similar functions on different molecules.
As well as the evolution of new metabolic pathways, evolution can also cause the loss of metabolic functions. For example, in some metabolic processes that are not essential for survival are lost and preformed amino acids, nucleotides and carbohydrates may instead be scavenged from the host. Similar reduced metabolic capabilities are seen in endosymbiont organisms.
An idea of the complexity of the metabolic networks in cells that contain thousands of different enzymes is given by the figure showing the interactions between just 43 proteins and 40 metabolites to the right: the sequences of genomes provide lists containing anything up to 26.500 genes. However, it is now possible to use this genomic data to reconstruct complete networks of biochemical reactions and produce more Holism mathematical models that may explain and predict their behavior. These models are especially powerful when used to integrate the pathway and metabolite data obtained through classical methods with data on gene expression from proteomics and DNA microarray studies. Using these techniques, a model of human metabolism has now been produced, which will guide future drug discovery and biochemical research. These models are now used in Network theory, to classify human diseases into groups that share common proteins or metabolites.
Bacterial metabolic networks are a striking example of bow-tie organization, an architecture able to input a wide range of nutrients and produce a large variety of products and complex macromolecules using a relatively few intermediate common currencies.
A major technological application of this information is metabolic engineering. Here, organisms such as yeast, plants or bacteria are genetically modified to make them more useful in biotechnology and aid the production of such as or industrial chemicals such as 1,3-propanediol and shikimic acid. These genetic modifications usually aim to reduce the amount of energy used to produce the product, increase yields and reduce the production of wastes.
Ibn al-Nafis described metabolism in his 1260 AD work titled Al-Risalah al-Kamiliyyah fil Siera al-Nabawiyyah (The Treatise of Kamil on the Prophet's Biography) which included the following phrase "Both the body and its parts are in a continuous state of dissolution and nourishment, so they are inevitably undergoing permanent change."
In these early studies, the mechanisms of these metabolic processes had not been identified and a vitalism was thought to animate living tissue. In the 19th century, when studying the fermentation of sugar to ethanol by yeast, Louis Pasteur concluded that fermentation was catalyzed by substances within the yeast cells he called "ferments". He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells." This discovery, along with the publication by Friedrich Wöhler in 1828 of a paper on the chemical synthesis of urea, and is notable for being the first organic compound prepared from wholly inorganic precursors. Wöhler's urea synthesis showed that organic compounds could be created from inorganic precursors, disputing the vital force theory that dominated early 19th-century science. Modern analyses consider this achievement as foundational for unifying organic and inorganic chemistry.
It was the discovery of at the beginning of the 20th century by Eduard Buchner that separated the study of the chemical reactions of metabolism from the biological study of cells, and marked the beginnings of biochemistry.Eduard Buchner's 1907 Nobel lecture at http://nobelprize.org Accessed 20 March 2007 The mass of biochemical knowledge grew rapidly throughout the early 20th century. One of the most prolific of these modern biochemists was Hans Krebs who made huge contributions to the study of metabolism. He discovered the urea cycle and later, working with Hans Kornberg, the citric acid cycle and the glyoxylate cycle. Modern biochemical research has been greatly aided by the development of new techniques such as chromatography, NMR spectroscopy, electron microscopy and molecular dynamics simulations. These techniques have allowed the discovery and detailed analysis of the many molecules and metabolic pathways in cells.
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