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Metabolism
Metabolism
(from Greek: μεταβολή metabolē, "change") is the set of life-sustaining chemical transformations within the cells of organisms. The three main purposes of metabolism are the conversion of food/fuel to energy to run cellular processes, the conversion of food/fuel to building blocks for proteins, lipids, nucleic acids, and some carbohydrates, and the elimination of nitrogenous wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. The word metabolism can also refer to the sum of all chemical reactions that occur in living organisms, including digestion and the transport of substances into and between different cells, in which case the set of reactions within the cells is called intermediary metabolism or intermediate metabolism. Metabolism
Metabolism
is usually divided into two categories: catabolism, the breaking down of organic matter for example, the breaking down of glucose to pyruvate, by cellular respiration, and anabolism, the building up of components of cells such as proteins and nucleic acids. Usually, breaking down releases energy and building up 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, by a sequence of enzymes. Enzymes
Enzymes
are crucial to metabolism because they allow organisms to drive desirable reactions that require energy that will not occur by themselves, by coupling them to spontaneous reactions that release energy. Enzymes act as catalysts that allow the reactions to proceed more rapidly. Enzymes
Enzymes
also allow the regulation of metabolic pathways in response to changes in the cell's environment or to signals from other cells. The metabolic system of a particular organism determines which substances it will find nutritious and which poisonous. For example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals.[1] The speed of metabolism, the metabolic rate, influences how much food an organism will require, and also affects how it is able to obtain that food. A striking feature of metabolism is the similarity of the basic metabolic pathways and components between even vastly different species.[2] For example, the set of carboxylic acids 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
Escherichia coli
and huge multicellular organisms like elephants.[3] These striking similarities in metabolic pathways are likely due to their early appearance in evolutionary history, and their retention because of their efficacy.[4][5]

Contents

1 Key biochemicals

1.1 Amino acids and proteins 1.2 Lipids 1.3 Carbohydrates 1.4 Nucleotides 1.5 Coenzymes 1.6 Minerals and cofactors

2 Catabolism

2.1 Digestion 2.2 Energy
Energy
from organic compounds

3 Energy
Energy
transformations

3.1 Oxidative phosphorylation 3.2 Energy
Energy
from inorganic compounds 3.3 Energy
Energy
from light

4 Anabolism

4.1 Carbon
Carbon
fixation 4.2 Carbohydrates and glycans 4.3 Fatty acids, isoprenoids and steroids 4.4 Proteins 4.5 Nucleotide
Nucleotide
synthesis and salvage

5 Xenobiotics and redox metabolism 6 Thermodynamics of living organisms 7 Regulation and control 8 Evolution 9 Investigation and manipulation 10 History 11 See also 12 References 13 Further reading 14 External links

Key biochemicals[edit] Further information: Biomolecule, Cell (biology), and Biochemistry

Structure of a triacylglycerol lipid

This is a diagram depicting a large set of human metabolic pathways.

Most of the structures that make up animals, plants and microbes are made from three basic classes of molecule: amino acids, carbohydrates and lipids (often called fats). As these molecules are vital for life, metabolic reactions either focus on making these molecules during the construction of cells and tissues, or by breaking them down and using them as a source of energy, by their digestion. These biochemicals can be joined together to make polymers such as DNA
DNA
and proteins, essential macromolecules of life.

Type of molecule Name of monomer forms Name of polymer forms Examples of polymer forms

Amino acids Amino acids Proteins (made of polypeptides) Fibrous proteins and globular proteins

Carbohydrates Monosaccharides Polysaccharides Starch, glycogen and cellulose

Nucleic acids Nucleotides Polynucleotides DNA
DNA
and RNA

Amino acids and proteins[edit] Proteins are made of amino acids arranged in a linear chain joined together by peptide bonds. Many proteins are enzymes that catalyze the chemical reactions in metabolism. Other proteins have structural or mechanical functions, such as those that form the cytoskeleton, a system of scaffolding that maintains the cell shape.[6] Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes, and the cell cycle.[7] Amino acids also contribute to cellular energy metabolism by providing a carbon source for entry into the citric acid cycle (tricarboxylic acid cycle),[8] especially when a primary source of energy, such as glucose, is scarce, or when cells undergo metabolic stress.[9] Lipids[edit] Lipids are the most diverse group of biochemicals. Their main structural uses are as part of biological membranes both internal and external, such as the cell membrane, or as a source of energy.[7] Lipids are usually defined as hydrophobic or amphipathic biological molecules but will dissolve in organic solvents such as benzene or chloroform.[10] The fats are a large group of compounds that contain fatty acids and glycerol; a glycerol molecule attached to three fatty acid esters is called a triacylglyceride.[11] Several variations on this basic structure exist, including alternate backbones such as sphingosine in the sphingolipids, and hydrophilic groups such as phosphate as in phospholipids. Steroids such as cholesterol are another major class of lipids.[12] Carbohydrates[edit]

Glucose
Glucose
can exist in both a straight-chain and ring form.

Carbohydrates are aldehydes or ketones, with many hydroxyl groups attached, that can exist as straight chains or rings. Carbohydrates are the most abundant biological molecules, and fill numerous roles, such as the storage and transport of energy (starch, glycogen) and structural components (cellulose in plants, chitin in animals).[7] The basic carbohydrate units are called monosaccharides and include galactose, fructose, and most importantly glucose. Monosaccharides
Monosaccharides
can be linked together to form polysaccharides in almost limitless ways.[13] Nucleotides[edit] The two nucleic acids, DNA
DNA
and RNA, are polymers of nucleotides. Each nucleotide is composed of a phosphate attached to a ribose or deoxyribose sugar group which is attached to a nitrogenous base. Nucleic acids are critical for the storage and use of genetic information, and its interpretation through the processes of transcription and protein biosynthesis.[7] This information is protected by DNA
DNA
repair mechanisms and propagated through DNA replication. Many viruses have an RNA
RNA
genome, such as HIV, which uses reverse transcription to create a DNA
DNA
template from its viral RNA genome.[14] RNA
RNA
in ribozymes such as spliceosomes and ribosomes is similar to enzymes as it can catalyze chemical reactions. Individual nucleosides are made by attaching a nucleobase to a ribose sugar. These bases are heterocyclic rings containing nitrogen, classified as purines or pyrimidines. Nucleotides also act as coenzymes in metabolic-group-transfer reactions.[15] Coenzymes[edit]

Structure of the coenzyme acetyl-CoA.The transferable acetyl group is bonded to the sulfur atom at the extreme left.

Main article: Coenzyme Metabolism
Metabolism
involves a vast array of chemical reactions, but most fall under a few basic types of reactions that involve the transfer of functional groups of atoms and their bonds within molecules.[16] This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions.[15] These group-transfer intermediates are called coenzymes. Each class of group-transfer reactions is carried out by a particular coenzyme, which is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. These coenzymes are therefore continuously made, consumed and then recycled.[17] One central coenzyme is adenosine triphosphate (ATP), the universal 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.[17] ATP acts as a bridge between catabolism and anabolism. Catabolism
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.[18] Nicotinamide adenine dinucleotide
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 dehydrogenases remove electrons from their substrates and reduce NAD+ into NADH. This reduced form of the coenzyme is then a substrate for any of the reductases in the cell that need to reduce their substrates.[19] Nicotinamide adenine dinucleotide
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
NADPH
is used in anabolic reactions.

Structure of hemoglobin. The protein subunits are in red and blue, and the iron-containing heme groups in green. From PDB: 1GZX​.

Minerals and cofactors[edit] Further information: Metal metabolism
Metal metabolism
and Bioinorganic chemistry Inorganic elements play critical roles in metabolism; some are abundant (e.g. sodium and potassium) while others function at minute concentrations. About 99% of a mammal's mass is made up of the elements carbon, nitrogen, calcium, sodium, chlorine, potassium, hydrogen, phosphorus, oxygen and sulfur.[20] Organic compounds (proteins, lipids and carbohydrates) contain the majority of the carbon and nitrogen; most of the oxygen and hydrogen is present as water.[20] The abundant inorganic elements act as ionic electrolytes. The most important ions are sodium, potassium, calcium, magnesium, chloride, phosphate and the organic ion bicarbonate. The maintenance of precise ion gradients across cell membranes maintains osmotic pressure and pH.[21] Ions are also critical for nerve and muscle function, as action potentials in these tissues are produced by the exchange of electrolytes between the extracellular fluid and the cell's fluid, the cytosol.[22] Electrolytes enter and leave cells through proteins in the cell membrane called ion channels. For example, muscle contraction depends upon the movement of calcium, sodium and potassium through ion channels in the cell membrane and T-tubules.[23] Transition metals are usually present as trace elements in organisms, with zinc and iron being most abundant of those.[24][25] These metals are used in some proteins as cofactors and are essential for the activity of enzymes such as catalase and oxygen-carrier proteins such as hemoglobin.[26] Metal cofactors are bound tightly to specific sites in proteins; although enzyme cofactors can be modified during catalysis, they always return to their original state by the end of the reaction catalyzed. Metal micronutrients are taken up into organisms by specific transporters and bind to storage proteins such as ferritin or metallothionein when not in use.[27][28] Catabolism[edit] Catabolism
Catabolism
is the set of metabolic processes that break down large molecules. These include breaking down and oxidizing food molecules. The purpose of the catabolic reactions is to provide the energy and components needed by anabolic reactions which build molecules. The exact nature of these catabolic reactions differ from organism to organism, and organisms can be classified based on their sources of energy and carbon (their primary nutritional groups), as shown in the table below. Organic molecules are used as a source of energy by organotrophs, while lithotrophs use inorganic substrates, and phototrophs capture sunlight as chemical energy. However, all these different forms of metabolism depend on redox reactions that involve the transfer of electrons from reduced donor molecules such as organic molecules, water, ammonia, hydrogen sulfide or ferrous ions to acceptor molecules such as oxygen, nitrate or sulfate.[29] In animals, these reactions involve complex organic molecules that are broken down to simpler molecules, such as carbon dioxide and water. In photosynthetic organisms, such as plants and cyanobacteria, these electron-transfer reactions do not release energy but are used as a way of storing energy absorbed from sunlight.[30]

Classification of organisms based on their metabolism

Energy
Energy
source sunlight photo-   -troph

Preformed molecules chemo-

Electron donor organic compound   organo-  

inorganic compound litho-

Carbon
Carbon
source organic compound   hetero-

inorganic compound auto-

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 proteins, polysaccharides or lipids, are digested into their smaller components outside cells. Next, these smaller molecules are taken up by cells and converted to smaller molecules, usually acetyl coenzyme A (acetyl-CoA), which releases some energy. Finally, the acetyl group on the CoA is oxidised to water and carbon dioxide in the citric acid cycle and electron transport chain, releasing the energy that is stored by reducing the coenzyme nicotinamide adenine dinucleotide (NAD+) into NADH. Digestion[edit] Further information: Digestion
Digestion
and Gastrointestinal tract Macromolecules
Macromolecules
such as starch, cellulose or proteins cannot be rapidly taken up by cells and must be broken into their smaller units before they can be used in cell metabolism. Several common classes of enzymes digest these polymers. These digestive enzymes include proteases that digest proteins into amino acids, as well as glycoside hydrolases that digest polysaccharides into simple sugars known as monosaccharides. Microbes simply secrete digestive enzymes into their surroundings,[31][32] while animals only secrete these enzymes from specialized cells in their guts, including the stomach and pancreas, and salivary glands.[33] The amino acids or sugars released by these extracellular enzymes are then pumped into cells by active transport proteins.[34][35]

A simplified outline of the catabolism of proteins, carbohydrates and fats

Energy
Energy
from organic compounds[edit] Further information: Cellular respiration, Fermentation (biochemistry), Carbohydrate
Carbohydrate
catabolism, Fat
Fat
catabolism, and Protein catabolism Carbohydrate
Carbohydrate
catabolism is the breakdown of carbohydrates into smaller units. Carbohydrates are usually taken into cells once they have been digested into monosaccharides.[36] Once inside, the major route of breakdown is glycolysis, where sugars such as glucose and fructose are converted into pyruvate and some ATP is generated.[37] Pyruvate
Pyruvate
is an intermediate in several metabolic pathways, but the majority is converted to acetyl-CoA through aerobic (with oxygen) glycolysis and fed into the citric acid cycle. Although some more ATP is generated in the citric acid cycle, the most important product is NADH, which is made from NAD+ as the acetyl-CoA is oxidized. This oxidation releases carbon dioxide as a waste product. In anaerobic conditions, glycolysis produces lactate, through the enzyme lactate dehydrogenase re-oxidizing NADH to NAD+ for re-use in glycolysis. An alternative route for glucose breakdown is the pentose phosphate pathway, which reduces the coenzyme NADPH
NADPH
and produces pentose sugars such as ribose, the sugar component of nucleic acids. Fats are catabolised 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 because carbohydrates contain more oxygen in their structures. 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.[38] Amino acids are either used to synthesize proteins and other biomolecules, or oxidized to urea and carbon dioxide as a source of energy.[39] 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 the deamination of glutamate forms α-ketoglutarate.[40] The glucogenic amino acids can also be converted into glucose, through gluconeogenesis (discussed below).[41] Energy
Energy
transformations[edit] Oxidative phosphorylation[edit] Further information: Oxidative phosphorylation, Chemiosmosis, and Mitochondrion In oxidative phosphorylation, the electrons removed from organic molecules in areas such as the protagon acid cycle are transferred to oxygen and the energy released is used to make ATP. This is done in eukaryotes by a series of proteins in the membranes of mitochondria called the electron transport chain. In prokaryotes, these proteins are found in the cell's inner membrane.[42] These proteins use the energy released from passing electrons from reduced molecules like NADH onto oxygen to pump protons across a membrane.[43]

Mechanism of ATP synthase. ATP is shown in red, ADP and phosphate in pink and the rotating stalk subunit in black.

Pumping protons out of the mitochondria creates a proton concentration difference across the membrane and generates an electrochemical gradient.[44] This force drives protons back into the mitochondrion through the base of an enzyme called ATP synthase. The flow of protons makes the stalk subunit rotate, causing the active site of the synthase domain to change shape and phosphorylate adenosine diphosphate – turning it into ATP.[17] Energy
Energy
from inorganic compounds[edit] Further information: Microbial metabolism
Microbial metabolism
and Nitrogen
Nitrogen
cycle Chemolithotrophy is a type of metabolism found in prokaryotes where energy is obtained from the oxidation of inorganic compounds. These organisms can use hydrogen,[45] reduced sulfur compounds (such as sulfide, hydrogen sulfide and thiosulfate),[1] ferrous iron (FeII)[46] or ammonia[47] as sources of reducing power and they gain energy from the oxidation of these compounds with electron acceptors such as oxygen or nitrite.[48] These microbial processes are important in global biogeochemical cycles such as acetogenesis, nitrification and denitrification and are critical for soil fertility.[49][50] Energy
Energy
from light[edit] Further information: Phototroph, Photophosphorylation, and Chloroplast The energy in sunlight is captured by plants, cyanobacteria, purple bacteria, green sulfur bacteria and some protists. This process is often coupled to the conversion of carbon dioxide into organic compounds, as part of photosynthesis, which is discussed below. The energy capture and carbon fixation systems can however operate separately in prokaryotes, as purple bacteria and green sulfur bacteria can use sunlight as a source of energy, while switching between carbon fixation and the fermentation of organic compounds.[51][52] 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.[17] The electrons needed to drive this electron transport chain come from light-gathering proteins called photosynthetic reaction centres or rhodopsins. Reaction centers are classed into two types depending on the type of photosynthetic pigment present, with most photosynthetic bacteria only having one type, while plants and cyanobacteria have two.[53] In plants, algae, and cyanobacteria, photosystem II 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.[30] These protons move back through the membrane as they drive the ATP synthase, as before. The electrons then flow through photosystem I and can then either be used to reduce the coenzyme NADP+, for use in the Calvin cycle, which is discussed below, or recycled for further ATP generation.[54] Anabolism[edit] Further information: Anabolism Anabolism is the set of constructive metabolic processes where the energy released by catabolism is used to synthesize complex molecules. In general, the complex molecules that make up cellular structures are constructed step-by-step from small and simple precursors. Anabolism involves three basic stages. First, the production of precursors such as amino acids, monosaccharides, isoprenoids and nucleotides, secondly, their activation into reactive forms using energy from ATP, and thirdly, the assembly of these precursors into complex molecules such as proteins, polysaccharides, lipids and nucleic acids. Organisms
Organisms
differ according to the number of constructed molecules in their cells. Autotrophs such as plants can construct the complex organic molecules in cells such as polysaccharides and proteins from simple molecules like carbon dioxide and water. Heterotrophs, on the other hand, require a source of more complex substances, such as monosaccharides and amino acids, to produce these complex molecules. Organisms
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 inorganic oxidation reactions. Carbon
Carbon
fixation[edit] Further information: Photosynthesis, Carbon
Carbon
fixation, and Chemosynthesis

Plant
Plant
cells (bounded by purple walls) filled with chloroplasts (green), which are the site of photosynthesis

Photosynthesis
Photosynthesis
is the synthesis of carbohydrates from sunlight and carbon dioxide (CO2). In plants, cyanobacteria and algae, oxygenic photosynthesis splits water, with oxygen produced as a waste product. This process uses the ATP and NADPH
NADPH
produced by the photosynthetic reaction centres, as described above, to convert CO2 into glycerate 3-phosphate, which can then be converted into glucose. This carbon-fixation reaction is carried out by the enzyme RuBisCO
RuBisCO
as part of the Calvin – Benson cycle.[55] Three types of photosynthesis occur in plants, C3 carbon fixation, C4 carbon fixation
C4 carbon fixation
and CAM photosynthesis. These differ by the route that carbon dioxide takes to the Calvin cycle, with C3 plants fixing CO2 directly, while C4 and CAM photosynthesis incorporate the CO2 into other compounds first, as adaptations to deal with intense sunlight and dry conditions.[56] In photosynthetic prokaryotes the mechanisms of carbon fixation are more diverse. Here, carbon dioxide can be fixed by the Calvin – Benson cycle, a reversed citric acid cycle,[57] or the carboxylation of acetyl-CoA.[58][59] Prokaryotic chemoautotrophs also fix CO2 through the Calvin – Benson cycle, but use energy from inorganic compounds to drive the reaction.[60] Carbohydrates and glycans[edit] Further information: Gluconeogenesis, Glyoxylate cycle, Glycogenesis, and Glycosylation In carbohydrate anabolism, simple organic acids can be converted into monosaccharides such as glucose and then used to assemble polysaccharides such as starch. The generation of glucose from compounds like pyruvate, lactate, glycerol, glycerate 3-phosphate and amino acids is called gluconeogenesis. Gluconeogenesis
Gluconeogenesis
converts pyruvate to glucose-6-phosphate through a series of intermediates, many of which are shared with glycolysis.[37] However, this pathway is not simply glycolysis run in reverse, as several steps are catalyzed by non-glycolytic enzymes. This is important as it allows the formation and breakdown of glucose to be regulated separately, and prevents both pathways from running simultaneously in a futile cycle.[61][62] Although fat is a common way of storing energy, in vertebrates such as humans the fatty acids 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.[63] As a result, after long-term starvation, vertebrates need to produce ketone bodies from fatty acids to replace glucose in tissues such as the brain that cannot metabolize fatty acids.[64] 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.[63][65] Polysaccharides and glycans are made by the sequential addition of monosaccharides by glycosyltransferase from a reactive sugar-phosphate donor such as uridine diphosphate glucose (UDP-glucose) 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.[66] The polysaccharides produced can have structural or metabolic functions themselves, or be transferred to lipids and proteins by enzymes called oligosaccharyltransferases.[67][68] Fatty acids, isoprenoids and steroids[edit] Further information: Fatty acid
Fatty acid
synthesis and Steroid
Steroid
metabolism

Simplified version of the steroid synthesis pathway with the intermediates isopentenyl pyrophosphate (IPP), dimethylallyl pyrophosphate (DMAPP), geranyl pyrophosphate (GPP) and squalene shown. Some intermediates are omitted for clarity.

Fatty acids are made by fatty acid synthases that polymerize and then reduce acetyl-CoA units. The acyl chains in the fatty acids are extended by a cycle of reactions that add the acyl group, reduce it to an alcohol, dehydrate it to an alkene group and then reduce it again to an alkane group. The enzymes of fatty acid biosynthesis are divided into two groups: in animals and fungi, all these fatty acid synthase reactions are carried out by a single multifunctional type I protein,[69] while in plant plastids and bacteria separate type II enzymes perform each step in the pathway.[70][71] Terpenes and isoprenoids are a large class of lipids that include the carotenoids and form the largest class of plant natural products.[72] These compounds are made by the assembly and modification of isoprene units donated from the reactive precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate.[73] These precursors can be made in different ways. In animals and archaea, the mevalonate pathway produces these compounds from acetyl-CoA,[74] while in plants and bacteria the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates.[73][75] One important reaction that uses these activated isoprene donors is steroid biosynthesis. Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol.[76] Lanosterol
Lanosterol
can then be converted into other steroids such as cholesterol and ergosterol.[76][77] Proteins[edit] Further information: Protein
Protein
biosynthesis and Amino acid
Amino acid
synthesis Organisms
Organisms
vary in their ability to synthesize the 20 common amino acids. Most bacteria and plants can synthesize all twenty, but mammals can only synthesize eleven nonessential amino acids, so nine essential amino acids must be obtained from food.[7] Some simple parasites, such as the bacteria Mycoplasma pneumoniae, lack all amino acid synthesis and take their amino acids directly from their hosts.[78] All amino acids are synthesized from intermediates in glycolysis, the citric acid cycle, or the pentose phosphate pathway. Nitrogen
Nitrogen
is provided by glutamate and glutamine. Amino acid
Amino acid
synthesis depends on the formation of the appropriate alpha-keto acid, which is then transaminated to form an amino acid.[79] Amino acids are made into proteins by being joined together in a chain of peptide bonds. 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
RNA
molecule through an ester bond. This aminoacyl-t RNA
RNA
precursor is produced in an ATP-dependent reaction carried out by an aminoacyl tRNA synthetase.[80] This aminoacyl-t RNA
RNA
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.[81] Nucleotide
Nucleotide
synthesis and salvage[edit] Further information: Nucleotide
Nucleotide
salvage, Pyrimidine
Pyrimidine
biosynthesis, and Purine
Purine
§ Metabolism Nucleotides are made from amino acids, carbon dioxide and formic acid in pathways that require large amounts of metabolic energy.[82] Consequently, most organisms have efficient systems to salvage preformed nucleotides.[82][83] Purines are synthesized as nucleosides (bases attached to ribose).[84] Both adenine and guanine are made from the precursor nucleoside inosine monophosphate, which is synthesized using atoms from the amino acids glycine, glutamine, and aspartic acid, as well as formate transferred from the coenzyme tetrahydrofolate. Pyrimidines, on the other hand, are synthesized from the base orotate, which is formed from glutamine and aspartate.[85] Xenobiotics and redox metabolism[edit] Further information: Xenobiotic metabolism, Drug
Drug
metabolism, Alcohol metabolism, and Antioxidant All organisms are constantly exposed to compounds that they cannot use as foods and would be harmful if they accumulated in cells, as they have no metabolic function. These potentially damaging compounds are called xenobiotics.[86] Xenobiotics such as synthetic drugs, natural poisons and antibiotics are detoxified by a set of xenobiotic-metabolizing enzymes. In humans, these include cytochrome P450 oxidases,[87] UDP-glucuronosyltransferases,[88] and glutathione S-transferases.[89] This system of enzymes acts in three stages to firstly oxidize the xenobiotic (phase I) and then conjugate water-soluble groups onto the molecule (phase II). The modified water-soluble xenobiotic can then be pumped out of cells and in multicellular organisms may be further metabolized before being excreted (phase III). In ecology, these reactions are particularly important in microbial biodegradation of pollutants and the bioremediation of contaminated land and oil spills.[90] Many of these microbial reactions are shared with multicellular organisms, but due to the incredible diversity of types of microbes these organisms are able to deal with a far wider range of xenobiotics than multicellular organisms, and can degrade even persistent organic pollutants such as organochloride compounds.[91] A related problem for aerobic organisms is oxidative stress.[92] Here, processes including oxidative phosphorylation and the formation of disulfide bonds during protein folding produce reactive oxygen species such as hydrogen peroxide.[93] These damaging oxidants are removed by antioxidant metabolites such as glutathione and enzymes such as catalases and peroxidases.[94][95] Thermodynamics of living organisms[edit] Further information: Biological thermodynamics Living organisms must obey the laws of thermodynamics, which describe the transfer of heat and work. The second law of thermodynamics states that in any closed system, the amount of entropy (disorder) cannot decrease. Although living organisms' amazing complexity appears to contradict this law, life is possible as all organisms are open systems that exchange matter and energy with their surroundings. Thus living systems are not in equilibrium, but instead are dissipative systems that maintain their state of high complexity by causing a larger increase in the entropy of their environments.[96] The metabolism of a cell achieves this by coupling the spontaneous processes of catabolism to the non-spontaneous processes of anabolism. In thermodynamic terms, metabolism maintains order by creating disorder.[97] Regulation and control[edit] Further information: Metabolic pathway, Metabolic control analysis, Hormone, Regulatory enzymes, and Cell signaling As the environments of most organisms are constantly changing, the reactions of metabolism must be finely regulated to maintain a constant set of conditions within cells, a condition called homeostasis.[98][99] Metabolic regulation also allows organisms to respond to signals and interact actively with their environments.[100] Two closely linked concepts are important for understanding how metabolic pathways are controlled. Firstly, the regulation of an enzyme in a pathway is how its activity is increased and decreased in response to signals. Secondly, the control exerted by this enzyme is the effect that these changes in its activity have on the overall rate of the pathway (the flux through the pathway).[101] For example, an enzyme may show large changes in activity (i.e. it is highly regulated) but if these changes have little effect on the flux of a metabolic pathway, then this enzyme is not involved in the control of the pathway.[102]

Effect of insulin on glucose uptake and metabolism. Insulin
Insulin
binds to its receptor (1), which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).

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.[101] This type of regulation often involves allosteric regulation of the activities of multiple enzymes in the pathway.[103] 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 soluble messengers such as hormones and growth factors and are detected by specific receptors on the cell surface.[104] These signals are then transmitted inside the cell by second messenger systems that often involved the phosphorylation of proteins.[105] A very well understood example of extrinsic control is the regulation of glucose metabolism by the hormone insulin.[106] Insulin
Insulin
is produced in response to rises in blood glucose levels. Binding of the hormone to insulin receptors on cells then activates a cascade of protein kinases that cause the cells to take up glucose and convert it into storage molecules such as fatty acids and glycogen.[107] 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
Insulin
causes glycogen synthesis by activating protein phosphatases and producing a decrease in the phosphorylation of these enzymes.[108] Evolution[edit] Further information: Molecular evolution
Molecular evolution
and Phylogenetics

Evolutionary tree showing the common ancestry of organisms from all three domains of life. Bacteria
Bacteria
are colored blue, eukaryotes red, and archaea green. Relative positions of some of the phyla included are shown around the tree.

The central pathways of metabolism described above, such as glycolysis and the citric acid cycle, are present in all three domains of living things and were present in the last universal common ancestor.[3][109] This universal ancestral cell was prokaryotic and probably a methanogen that had extensive amino acid, nucleotide, carbohydrate and lipid metabolism.[110][111] The retention of these ancient pathways during later evolution may be the result of these reactions having been an optimal solution to their particular metabolic problems, with pathways such as glycolysis and the citric acid cycle producing their end products highly efficiently and in a minimal number of steps.[4][5] The first pathways of enzyme-based metabolism may have been parts of purine nucleotide metabolism, while previous metabolic pathways were a part of the ancient RNA
RNA
world.[112] 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.[113] 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.[114] 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)[115] These recruitment processes result in an evolutionary enzymatic mosaic.[116] 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.[117] As well as the evolution of new metabolic pathways, evolution can also cause the loss of metabolic functions. For example, in some parasites metabolic processes that are not essential for survival are lost and preformed amino acids, nucleotides and carbohydrates may instead be scavenged from the host.[118] Similar reduced metabolic capabilities are seen in endosymbiotic organisms.[119] Investigation and manipulation[edit] Further information: Protein
Protein
methods, Proteomics, Metabolomics, and Metabolic network
Metabolic network
modelling

Metabolic network
Metabolic network
of the Arabidopsis thaliana
Arabidopsis thaliana
citric acid cycle. Enzymes
Enzymes
and metabolites are shown as red squares and the interactions between them as black lines.

Classically, metabolism is studied by a reductionist approach that focuses on a single metabolic pathway. Particularly valuable is the use of radioactive tracers at the whole-organism, tissue and cellular levels, which define the paths from precursors to final products by identifying radioactively labelled intermediates and products.[120] The enzymes that catalyze these chemical reactions can then be purified and their kinetics and responses to inhibitors investigated. A parallel approach is to identify the small molecules in a cell or tissue; the complete set of these molecules is called the metabolome. Overall, these studies give a good view of the structure and function of simple metabolic pathways, but are inadequate when applied to more complex systems such as the metabolism of a complete cell.[121] 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 45,000 genes.[122] However, it is now possible to use this genomic data to reconstruct complete networks of biochemical reactions and produce more holistic mathematical models that may explain and predict their behavior.[123] These models are especially powerful when used to integrate the pathway and metabolite data obtained through classical methods with data on gene expression from proteomic and DNA
DNA
microarray studies.[124] Using these techniques, a model of human metabolism has now been produced, which will guide future drug discovery and biochemical research.[125] These models are now used in network analysis, to classify human diseases into groups that share common proteins or metabolites.[126][127] Bacterial metabolic networks are a striking example of bow-tie[128][129][130] 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 drugs such as antibiotics or industrial chemicals such as 1,3-propanediol and shikimic acid.[131] These genetic modifications usually aim to reduce the amount of energy used to produce the product, increase yields and reduce the production of wastes.[132] History[edit] Further information: History of biochemistry
History of biochemistry
and History of molecular biology The term metabolism is derived from the Greek Μεταβολισμός – "Metabolismos" for "change", or "overthrow".[133]

Aristotle's metabolism as an open flow model

Aristotle's The Parts of Animals
The Parts of Animals
sets out enough details of his views on metabolism for an open flow model to be made. He believed that at each stage of the process, materials from food were transformed, with heat being released as the classical element of fire, and residual materials being excreted as urine, bile, or faeces.[134] Ibn al-Nafis
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."[135] The history of the scientific study of metabolism spans several centuries and has moved from examining whole animals in early studies, to examining individual metabolic reactions in modern biochemistry. The first controlled experiments in human metabolism were published by Santorio Santorio
Santorio Santorio
in 1614 in his book Ars de statica medicina.[136] He described how he weighed himself before and after eating, sleep, working, sex, fasting, drinking, and excreting. He found that most of the food he took in was lost through what he called "insensible perspiration".

Santorio Santorio
Santorio Santorio
in his steelyard balance, from Ars de statica medicina, first published 1614

In these early studies, the mechanisms of these metabolic processes had not been identified and a vital force was thought to animate living tissue.[137] In the 19th century, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur
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."[138] This discovery, along with the publication by Friedrich Wöhler in 1828 of a paper on the chemical synthesis of urea,[139] and is notable for being the first organic compound prepared from wholly inorganic precursors. This proved that the organic compounds and chemical reactions found in cells were no different in principle than any other part of chemistry. It was the discovery of enzymes at the beginning of the 20th century by Eduard Buchner
Eduard Buchner
that separated the study of the chemical reactions of metabolism from the biological study of cells, and marked the beginnings of biochemistry.[140] 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.[141] He discovered the urea cycle and later, working with Hans Kornberg, the citric acid cycle and the glyoxylate cycle.[142][65] Modern biochemical research has been greatly aided by the development of new techniques such as chromatography, X-ray diffraction, NMR spectroscopy, radioisotopic labelling, electron microscopy and molecular dynamics simulations. These techniques have allowed the discovery and detailed analysis of the many molecules and metabolic pathways in cells. See also[edit]

Metabolism
Metabolism
portal Underwater diving portal

Anthropogenic metabolism Antimetabolite Basal metabolic rate Calorimetry Isothermal microcalorimetry Inborn error of metabolism Iron-sulfur world theory, a "metabolism first" theory of the origin of life Metabolic disorder Primary nutritional groups Respirometry Stream metabolism Sulfur
Sulfur
metabolism Thermic effect of food Urban metabolism Water
Water
metabolism Overflow metabolism

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Further reading[edit]

Library resources about Metabolism

Online books Resources in your library Resources in other libraries

Introductory

Rose, S. and Mileusnic, R., The Chemistry of Life. (Penguin Press Science, 1999), ISBN 0-14-027273-9 Schneider, E. D. and Sagan, D., Into the Cool: Energy
Energy
Flow, Thermodynamics, and Life. (University Of Chicago Press, 2005), ISBN 0-226-73936-8 Lane, N., Oxygen: The Molecule
Molecule
that Made the World. (Oxford University Press, USA, 2004), ISBN 0-19-860783-0

Advanced

Price, N. and Stevens, L., Fundamentals of Enzymology: Cell and Molecular Biology of Catalytic Proteins. (Oxford University Press, 1999), ISBN 0-19-850229-X Berg, J. Tymoczko, J. and Stryer, L., Biochemistry. (W. H. Freeman and Company, 2002), ISBN 0-7167-4955-6 Cox, M. and Nelson, D. L., Lehninger Principles of Biochemistry. (Palgrave Macmillan, 2004), ISBN 0-7167-4339-6 Brock, T. D. Madigan, M. T. Martinko, J. and Parker J., Brock's Biology of Microorganisms. (Benjamin Cummings, 2002), ISBN 0-13-066271-2 Da Silva, J.J.R.F. and Williams, R. J. P., The Biological Chemistry of the Elements: The Inorganic Chemistry of Life. (Clarendon Press, 1991), ISBN 0-19-855598-9 Nicholls, D. G. and Ferguson, S. J., Bioenergetics. (Academic Press Inc., 2002), ISBN 0-12-518121-3

External links[edit]

Wikiversity has learning resources about Topic:Biochemistry

Wikibooks has more on the topic of: Metabolism

Look up metabolism in Wiktionary, the free dictionary.

General information

The Biochemistry
Biochemistry
of Metabolism Sparknotes SAT biochemistry Overview of biochemistry. School level. MIT Biology Hypertextbook Undergraduate-level guide to molecular biology.

Human metabolism

Topics in Medical Biochemistry
Biochemistry
Guide to human metabolic pathways. School level. http://themedicalbiochemistrypage.org/ THE Medical Biochemistry
Biochemistry
Page] Comprehensive resource on human metabolism.

Databases

Flow Chart of Metabolic Pathways at ExPASy IUBMB-Nicholson Metabolic Pathways Chart SuperCYP: Database for Drug-Cytochrome-Metabolism

Metabolic pathways

Metabolism
Metabolism
reference Pathway The Nitrogen
Nitrogen
cycle and Nitrogen
Nitrogen
fixation at the Wayback Machine (archive index)

Articles related to Metabolism

v t e

Metabolism
Metabolism
map

Carbon Fixation Photo- respiration Pentose Phosphate Pathway Citric Acid Cycle Glyoxylate Cycle Urea Cycle Fatty Acid Synthesis Fatty Acid Elongation Beta Oxidation Peroxisomal Beta Oxidation

Glyco- genolysis Glyco- genesis Glyco- lysis Gluconeo- genesis Decarb- oxylation Fermentation Keto- lysis Keto- genesis feeders to Gluconeo- genesis Direct / C4 / CAM Carbon
Carbon
Intake Light Reaction Oxidative Phosphorylation Amino Acid Deamination Citrate Shuttle Lipogenesis Lipolysis Steroidogenesis MVA Pathway MEP Pathway Shikimate Pathway Transcription & Replication Translation Proteolysis Glycosy- lation

Sugar Acids Double/Multiple Sugars & Glycans Simple Sugars Inositol-P Amino Sugars & Sialic Acids Nucleotide
Nucleotide
Sugars Hexose-P Triose-P Glycerol P-glycerates Pentose-P Tetrose-P Propionyl -CoA Succinate Acetyl -CoA Pentose-P P-glycerates Glyoxylate Photosystems Pyruvate Lactate Acetyl -CoA Citrate Oxalo- acetate Malate Succinyl -CoA α-Keto- glutarate Ketone Bodies Respiratory Chain Serine
Serine
Group Alanine Branched-chain Amino Acids Aspartate Group Homoserine Group & Lysine Glutamate Group & Proline Arginine Creatine & Polyamines Ketogenic & Glucogenic Amino Acids Amino Acids Shikimate Aromatic Amino Acids & Histidine Ascorbate ( Vitamin
Vitamin
C) δ-ALA Bile Pigments Hemes Cobalamins ( Vitamin
Vitamin
B12) Various Vitamin
Vitamin
B's Calciferols ( Vitamin
Vitamin
D) Retinoids ( Vitamin
Vitamin
A) Quinones ( Vitamin
Vitamin
K) & Carotenoids ( Vitamin
Vitamin
E) Cofactors Vitamins & Minerals Antioxidants PRPP Nucleotides Nucleic Acids Proteins Glycoproteins & Proteoglycans Chlorophylls MEP MVA Acetyl -CoA Polyketides Terpenoid Backbones Terpenoids & Carotenoids ( Vitamin
Vitamin
A) Cholesterol Bile
Bile
Acids Glycero- phospholipids Glycerolipids Acyl-CoA Fatty Acids Glyco- sphingolipids Sphingolipids Waxes Polyunsaturated Fatty Acids Neurotransmitters & Thyroid Hormones Steroids Endo- cannabinoids Eicosanoids

Major metabolic pathways in metro-style map. Click any text (name of pathway or metabolites) to link to the corresponding article. Single lines: pathways common to most lifeforms. Double lines: pathways not in humans (occurs in e.g. plants, fungi, prokaryotes). Orange nodes: carbohydrate metabolism. Violet nodes: photosynthesis. Red nodes: cellular respiration. Pink nodes: cell signaling. Blue nodes: amino acid metabolism. Grey nodes: vitamin and cofactor metabolism. Brown nodes: nucleotide and protein metabolism. Green nodes: lipid metabolism.

v t e

Metabolism, catabolism, anabolism

General

Metabolic pathway Metabolic network Primary nutritional groups

Energy metabolism

Aerobic respiration

Glycolysis
Glycolysis
Pyruvate
Pyruvate
decarboxylation → Citric acid cycle
Citric acid cycle
Oxidative phosphorylation
Oxidative phosphorylation
(electron transport chain + ATP synthase)

Anaerobic respiration

Electron acceptors are other than oxygen

Fermentation

Glycolysis
Glycolysis
→ Substrate-level phosphorylation

ABE Ethanol Lactic acid

Specific paths

Protein
Protein
metabolism

Protein
Protein
synthesis Catabolism

Carbohydrate
Carbohydrate
metabolism (carbohydrate catabolism and anabolism)

Human

Glycolysis
Glycolysis
⇄ Gluconeogenesis

Glycogenolysis
Glycogenolysis
⇄ Glycogenesis

Pentose
Pentose
phosphate pathway Fructolysis Galactolysis

Glycosylation

N-linked O-linked

Nonhuman

Photosynthesis Anoxygenic photosynthesis Chemosynthesis Carbon
Carbon
fixation

Xylose metabolism Radiotrophism

Lipid
Lipid
metabolism (lipolysis, lipogenesis)

Fatty acid
Fatty acid
metabolism

Fatty acid
Fatty acid
degradation (Beta oxidation) Fatty acid
Fatty acid
synthesis

Other

Steroid
Steroid
metabolism Sphingolipid
Sphingolipid
metabolism Eicosanoid
Eicosanoid
metabolism Ketosis Reverse cholesterol transport

Amino acid

Amino acid
Amino acid
synthesis Urea
Urea
cycle

Nucleotide metabolism

Purine
Purine
metabolism Nucleotide
Nucleotide
salvage Pyrimidine
Pyrimidine
metabolism

Other

Metal metabolism

Iron
Iron
metabolism

Ethanol metabolism

v t e

Metabolism: carbohydrate metabolism: glycolysis/gluconeogenesis enzymes

Glycolysis

Hexokinase
Hexokinase
(HK1, HK2, HK3, Glucokinase)→/ Glucose
Glucose
6-phosphatase← Glucose
Glucose
isomerase Phosphofructokinase 1
Phosphofructokinase 1
(Liver, Muscle, Platelet)→/Fructose 1,6-bisphosphatase←

Fructose-bisphosphate aldolase
Fructose-bisphosphate aldolase
(Aldolase A, B, C) Triosephosphate isomerase

Glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate
dehydrogenase Phosphoglycerate kinase Phosphoglycerate mutase Enolase Pyruvate
Pyruvate
kinase (PKLR, PKM2)

Gluconeogenesis
Gluconeogenesis
only

to oxaloacetate:

Pyruvate
Pyruvate
carboxylase Phosphoenolpyruvate carboxykinase

from lactate (Cori cycle):

Lactate dehydrogenase

from alanine ( Alanine
Alanine
cycle):

Alanine
Alanine
transaminase

from glycerol:

Glycerol
Glycerol
kinase Glycerol
Glycerol
dehydrogenase

Regulatory

Fructose
Fructose
6-P,2-kinase:fructose 2,6-bisphosphatase

PFKFB1, PFKFB2, PFKFB3, PFKFB4

Bisphosphoglycerate mutase

v t e

Metabolism: carbohydrate metabolism fructose and galactose enzymes

Fructose
Fructose
/ Fructolysis

Hepatic fructokinase Aldolase B Triokinase

Sorbitol

Sorbitol
Sorbitol
dehydrogenase Aldose reductase

Galactose
Galactose
/ Galactolysis

Galactokinase Galactose-1-phosphate uridylyltransferase/UDP-glucose 4-epimerase Aldose reductase

Lactose

Lactose
Lactose
synthase Lactase

Mannose

Mannose
Mannose
phosphate isomerase

v t e

Metabolism: carbohydrate metabolism proteoglycan enzymes

glycosaminoglycan anabolism

L-xylulose reductase L-gulonolactone oxidase UDP-glucuronate 5'-epimerase Xylosyltransferase Sulfotransferase

Heparan sulfate EXT1 EXT2

Chondroitin sulfate PAPSS1 PAPSS2

glycosaminoglycan catabolism

Hunter, Hurler

Iduronate-2-sulfatase Iduronidase

Sanfilippo, Sly

Heparan sulfamidase N-acetyltransferase Alpha-N-acetylglucosaminidase Glucuronidase N-acetylglucosamine-6-sulfatase

Morquio/Maroteaux-Lamy

Arylsulfatase B Galactosamine-6 sulfatase Beta-galactosidase
Beta-galactosidase
(GLB1)

v t e

Metabolism: carbohydrate metabolism · glycoprotein enzymes

Anabolism

Dolichol kinase GCS1 Oligosaccharyltransferase

Catabolism

Neuraminidase Beta-galactosidase Hexosaminidase mannosidase

alpha-Mannosidase beta-mannosidase

Aspartylglucosaminidase Fucosidase NAGA

Transport

SLC17A5

M6P tagging

N-acetylglucosamine-1-phosphate transferase

v t e

Metabolism, lipid metabolism, glycolipid enzymes

Sphingolipid

To glycosphingolipid

Glycosyltransferase Sulfotransferase

To ceramide

From ganglioside Beta-galactosidase Hexosaminidase
Hexosaminidase
A Neuraminidase Glucocerebrosidase

From globoside Hexosaminidase
Hexosaminidase
B Alpha-galactosidase Beta-galactosidase Glucocerebrosidase

From sphingomyelin Sphingomyelin
Sphingomyelin
phosphodiesterase

Sphingomyelin
Sphingomyelin
phosphodiesterase 1

From sulfatide Arylsulfatase A Galactosylceramidase

To sphingosine

Ceramidase

ACER1 ACER2 ACER3 ASAH1 ASAH2 ASAH2B ASAH2C

Other

Sphingosine
Sphingosine
kinase

NCL

Palmitoyl protein thioesterase Tripeptidyl peptidase I CLN3 CLN5 CLN6 CLN8

Ceramide
Ceramide
synthesis

Serine
Serine
C-palmitoyltransferase (SPTLC1) Ceramide
Ceramide
glucosyltransferase (UGCG)

v t e

Metabolism: lipid metabolism - eicosanoid metabolism enzymes

Precursor

Phospholipase A2

Phospholipase C Diacylglycerol lipase

Prostanoids

Cyclooxygenase

PTGS1 PTGS2

PGD2 synthase

PGE synthase Prostaglandin-E2 9-reductase

PGI2 synthase

TXA synthase

Leukotrienes

5-Lipoxygenase activating protein/Arachidonate 5-lipoxygenase

LTA4 hydrolase (B4 synthesis)

LTC4 synthase Gamma-glutamyl transpeptidase LTD4 hydrolase

Ungrouped

HPGD

v t e

Metabolism: lipid metabolism / fatty acid metabolism, triglyceride and fatty acid enzymes

Synthesis

Malonyl-CoA
Malonyl-CoA
synthesis

ATP citrate lyase Acetyl-CoA
Acetyl-CoA
carboxylase

Fatty acid
Fatty acid
synthesis/ Fatty acid
Fatty acid
synthase

Beta-ketoacyl-ACP synthase Β-Ketoacyl ACP reductase 3-Hydroxyacyl ACP dehydrase Enoyl ACP reductase

Fatty acid
Fatty acid
desaturases

Stearoyl-CoA desaturase-1

Triacyl glycerol

Glycerol-3-phosphate dehydrogenase Thiokinase

Degradation

Acyl transport

Carnitine palmitoyltransferase I Carnitine-acylcarnitine translocase Carnitine palmitoyltransferase II

Beta oxidation

General

Acyl CoA dehydrogenase
Acyl CoA dehydrogenase
(ACADL ACADM ACADS ACADVL ACADSB) Enoyl-CoA hydratase

MTP: HADH HADHA HADHB

Acetyl-CoA
Acetyl-CoA
C-acyltransferase

Unsaturated

Enoyl CoA isomerase 2,4 Dienoyl-CoA reductase

Odd chain

Propionyl-CoA
Propionyl-CoA
carboxylase

Other

Hydroxyacyl- Coenzyme
Coenzyme
A dehydrogenase

To acetyl-CoA

Malonyl-CoA
Malonyl-CoA
decarboxylase

Aldehydes

Long-chain-aldehyde dehydrogenase

v t e

Metabolism: amino acid metabolism - urea cycle enzymes

Main cycle

mitochondrial matrix:

Carbamoyl phosphate synthetase I Ornithine transcarbamylase

cytosol:

Argininosuccinate synthetase Argininosuccinate lyase Arginase

Regulatory/transport

N-Acetylglutamate synthase Ornithine translocase

v t e

Enzymes
Enzymes
involved in neurotransmission

monoamine

histidine → histamine

anabolism:

Histidine
Histidine
decarboxylase

catabolism:

Histamine
Histamine
N-methyltransferase Diamine oxidase

tyrosine→dopamine→epinephrine

anabolism:

Tyrosine
Tyrosine
hydroxylase Aromatic L-amino acid decarboxylase Dopamine
Dopamine
beta-hydroxylase Phenylethanolamine N-methyltransferase

catabolism:

Catechol-O-methyl transferase Monoamine oxidase

A B

glutamate→GABA

anabolism:

Glutamate
Glutamate
decarboxylase

catabolism:

4-aminobutyrate transaminase

tryptophan→serotonin→melatonin

Tryptophan
Tryptophan
hydroxylase Aromatic L-amino acid decarboxylase Aralkylamine N-acetyltransferase Acetylserotonin O-methyltransferase

arginine→NO

Nitric oxide
Nitric oxide
synthase (NOS1, NOS2, NOS3)

choline→Acetylcholine

anabolism:

Choline
Choline
acetyltransferase

catabolism:

Cholinesterase
Cholinesterase
(Acetylcholinesterase, Butyrylcholinesterase)

v t e

Enzymes
Enzymes
involved in the metabolism of heme and porphyrin

Porphyrin
Porphyrin
biosynthesis

early mitochondrial:

Aminolevulinic acid
Aminolevulinic acid
synthase

ALAS1 ALAS2

cytosolic:

Porphobilinogen synthase Porphobilinogen deaminase Uroporphyrinogen III synthase Uroporphyrinogen III decarboxylase

late mitochondrial:

Coproporphyrinogen III oxidase Protoporphyrinogen oxidase Ferrochelatase

Heme
Heme
degradation to bile

spleen:

Heme
Heme
oxygenase Biliverdin reductase

liver:

glucuronosyltransferase

UGT1A1

v t e

Metabolism
Metabolism
of vitamins, coenzymes, and cofactors

Fat
Fat
soluble vitamins

Vitamin
Vitamin
A

Retinol binding protein

Vitamin
Vitamin
E

Alpha-tocopherol transfer protein

Vitamin
Vitamin
D

liver (Sterol 27-hydroxylase or CYP27A1) renal ( 25-Hydroxyvitamin D3 1-alpha-hydroxylase
25-Hydroxyvitamin D3 1-alpha-hydroxylase
or CYP27B1) degradation (1,25-Dihydroxyvitamin D3 24-hydroxylase or CYP24A1)

Vitamin
Vitamin
K

Vitamin
Vitamin
K epoxide reductase

Water
Water
soluble vitamins

Thiamine
Thiamine
(B1)

Thiamine
Thiamine
diphosphokinase

Niacin
Niacin
(B3)

Indoleamine 2,3-dioxygenase Formamidase

Pantothenic acid
Pantothenic acid
(B5)

Pantothenate kinase

Folic acid
Folic acid
(B9)

Dihydropteroate synthase Dihydrofolate reductase Serine
Serine
hydroxymethyltransferase

Methylenetetrahydrofolate reductase

Vitamin
Vitamin
B12

MMAA MMAB MMACHC MMADHC

Vitamin
Vitamin
C

L-gulonolactone oxidase

Riboflavin
Riboflavin
(B2)

Riboflavin
Riboflavin
kinase

Nonvitamin cofactors

Tetrahydrobiopterin

GTP cyclohydrolase I 6-pyruvoyltetrahydropterin synthase Sepiapterin reductase

PCBD1 PTS QDPR

Molybdenum cofactor

MOCS1 MOCS2 MOCS3 Gephyrin

v t e

Metabolism: Protein
Protein
metabolism, synthesis and catabolism enzymes

Essential amino acids are in Capitals

K→acetyl-CoA

LYSINE→

Saccharopine dehydrogenase Glutaryl-CoA dehydrogenase

LEUCINE→

Branched-chain amino acid
Branched-chain amino acid
aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Isovaleryl coenzyme A dehydrogenase Methylcrotonyl-CoA carboxylase Methylglutaconyl-CoA hydratase 3-hydroxy-3-methylglutaryl-CoA lyase

TRYPTOPHAN→

Indoleamine 2,3-dioxygenase/ Tryptophan
Tryptophan
2,3-dioxygenase Arylformamidase Kynureninase 3-hydroxyanthranilate oxidase Aminocarboxymuconate-semialdehyde decarboxylase Aminomuconate-semialdehyde dehydrogenase

PHENYLALANINE→tyrosine→

(see below)

G

G→pyruvate →citrate

glycine→serine→

Serine
Serine
hydroxymethyltransferase Serine
Serine
dehydratase

glycine→creatine: Guanidinoacetate N-methyltransferase Creatine
Creatine
kinase

alanine→

Alanine
Alanine
transaminase

cysteine→

D-cysteine desulfhydrase

threonine→

L-threonine dehydrogenase

G→glutamate→ α-ketoglutarate

HISTIDINE→

Histidine
Histidine
ammonia-lyase Urocanate hydratase Formiminotransferase cyclodeaminase

proline→

Proline
Proline
oxidase Pyrroline-5-carboxylate reductase 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1 PYCR1

arginine→

Ornithine aminotransferase Ornithine decarboxylase Agmatinase

→alpha-ketoglutarate→TCA

Glutamate
Glutamate
dehydrogenase

Other

cysteine+glutamate→glutathione: Gamma-glutamylcysteine synthetase Glutathione
Glutathione
synthetase Gamma-glutamyl transpeptidase

glutamate→glutamine: Glutamine
Glutamine
synthetase Glutaminase

G→propionyl-CoA→ succinyl-CoA

VALINE→

Branched-chain amino acid
Branched-chain amino acid
aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Enoyl-CoA hydratase 3-hydroxyisobutyryl-CoA hydrolase 3-hydroxyisobutyrate dehydrogenase Methylmalonate semialdehyde dehydrogenase

ISOLEUCINE→

Branched-chain amino acid
Branched-chain amino acid
aminotransferase Branched-chain alpha-keto acid dehydrogenase complex 3-hydroxy-2-methylbutyryl-CoA dehydrogenase

METHIONINE→

generation of homocysteine: Methionine
Methionine
adenosyltransferase Adenosylhomocysteinase

regeneration of methionine: Methionine
Methionine
synthase/Homocysteine methyltransferase Betaine-homocysteine methyltransferase

conversion to cysteine: Cystathionine beta synthase Cystathionine gamma-lyase

THREONINE→

Threonine
Threonine
aldolase

→succinyl-CoA→TCA

Propionyl-CoA
Propionyl-CoA
carboxylase Methylmalonyl CoA epimerase Methylmalonyl-CoA mutase

G→fumarate

PHENYLALANINE→tyrosine→

Phenylalanine
Phenylalanine
hydroxylase Tyrosine
Tyrosine
aminotransferase 4-Hydroxyphenylpyruvate dioxygenase Homogentisate 1,2-dioxygenase Fumarylacetoacetate hydrolase

tyrosine→melanin: Tyrosinase

G→oxaloacetate

asparagine→aspartate→

Asparaginase/ Asparagine
Asparagine
synthetase Aspartate
Aspartate
transaminase

v t e

Metabolism: amino acid metabolism nucleotide enzymes

Purine
Purine
metabolism

Anabolism

R5P→IMP:

Ribose-phosphate diphosphokinase Amidophosphoribosyltransferase Phosphoribosylglycinamide formyltransferase AIR synthetase (FGAM cyclase) Phosphoribosylaminoimidazole carboxylase Phosphoribosylaminoimidazolesuccinocarboxamide synthase IMP synthase

IMP→AMP:

Adenylosuccinate synthase Adenylosuccinate lyase reverse

AMP deaminase

IMP→GMP:

IMP dehydrogenase GMP synthase reverse

GMP reductase

Nucleotide
Nucleotide
salvage

Hypoxanthine-guanine phosphoribosyltransferase Adenine
Adenine
phosphoribosyltransferase

Catabolism

Adenosine deaminase Purine
Purine
nucleoside phosphorylase Guanine
Guanine
deaminase Xanthine oxidase Urate oxidase

Pyrimidine
Pyrimidine
metabolism

Anabolism

CAD

Carbamoyl phosphate synthase II Aspartate
Aspartate
carbamoyltransferase Dihydroorotase

Dihydroorotate dehydrogenase Orotidine 5'-phosphate decarboxylase/Uridine monophosphate synthetase

CTP synthetase

Catabolism

Dihydropyrimidine dehydrogenase Dihydropyrimidinase/DPYS Beta-ureidopropionase/UPB1

Deoxyribonucleotides

Ribonucleotide reductase Nucleoside-diphosphate kinase DCMP deaminase Thymidylate synthase Dihydrofolate reductase

v t e

Metabolism: lipid metabolism – ketones/cholesterol synthesis enzymes/steroid metabolism

Mevalonate pathway

To HMG-CoA

Acetyl- Coenzyme
Coenzyme
A acetyltransferase HMG-CoA
HMG-CoA
synthase (regulated step)

Ketogenesis

HMG-CoA
HMG-CoA
lyase 3-hydroxybutyrate dehydrogenase Thiophorase

To Mevalonic acid

HMG-CoA
HMG-CoA
reductase

To DMAPP

Mevalonate kinase Phosphomevalonate kinase Pyrophosphomevalonate decarboxylase Isopentenyl-diphosphate delta isomerase

Geranyl-

Dimethylallyltranstransferase Geranyl pyrophosphate

To cholesterol

To lanosterol

Farnesyl-diphosphate farnesyltransferase Squalene
Squalene
monooxygenase Lanosterol
Lanosterol
synthase

7-Dehydrocholesterol
7-Dehydrocholesterol
path

Lanosterol
Lanosterol
14α-demethylase Sterol-C5-desaturase-like 7-Dehydrocholesterol
7-Dehydrocholesterol
reductase

Desmosterol
Desmosterol
path

24-Dehydrocholesterol reductase

To Bile
Bile
acids

Cholesterol
Cholesterol
7α-hydroxylase Sterol 27-hydroxylase

Steroidogenesis

To pregnenolone

Cholesterol
Cholesterol
side-chain cleavage

To corticosteroids

aldosterone: 18-Hydroxylase

cortisol/cortisone: 17α-Hydroxylase 11β-HSD

1 2

both: 3β-HSD

1 2

21-Hydroxylase 11β-Hydroxylase

To sex hormones

To androgens

17α-Hydroxylase 17,20-Lyase 3β-HSD 17β-HSD 5α-Reductase

1 2

To estrogens

Aromatase 17β-HSD

Other/ungrouped

Steroid
Steroid
metabolism: sulfatase

Steroid
Steroid
sulfatase

sulfotransferase

SULT1A1 SULT2A1

Steroidogenic acute regulatory protein Cholesterol
Cholesterol
total synthesis Reverse cholesterol transport

v t e

Metabolism: carbohydrate metabolism · pentose phosphate pathway enzymes

oxidative

Glucose-6-phosphate
Glucose-6-phosphate
dehydrogenase 6-phosphogluconolactonase Phosphogluconate dehydrogenase

nonoxidative

Phosphopentose isomerase Phosphopentose epimerase Transketolase Transaldolase

v t e

Metabolism
Metabolism
- non-mevalonate pathway enzymes

DXP synthase DXP reductoisomerase 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase 4-hydroxy-3-methylbut-2-enyl diphosphate reductase

v t e

Food science

General

Allergy Engineering Microbiology Nutrition

Diet clinical

Processing Processing aids Quality Sensory analysis

Discrimination testing

Rheology Storage Technology

v t e

Food chemistry

Additives Carbohydrates Coloring Enzymes Essential fatty acids Flavors Fortification Lipids "Minerals" (Chemical elements) Proteins Vitamins Water

v t e

Food preservation

Biopreservation Canning Cold chain Curing Drying Fermentation Freeze-drying Freezing Hurdle technology Irradiation Jamming Jellying Jugging Modified atmosphere Pascalization Pickling Potting

Confit Potjevleesch

Salting Smoking Sugaring Tyndallization Vacuum packing

Food industry

Manufacturing Packaging Marketing Foodservice Fortification

v t e

Food safety

Adulterants, food contaminants

3-MCPD Aldicarb Cyanide Formaldehyde Lead poisoning Melamine Mercury in fish Sudan I

Flavorings

Monosodium glutamate
Monosodium glutamate
(MSG) Salt Sugar

High-fructose corn syrup

Microorganisms

Botulism Campylobacter jejuni Clostridium perfringens Escherichia coli
Escherichia coli
O104:H4 Escherichia coli
Escherichia coli
O157:H7 Hepatitis A Hepatitis E Listeria Norovirus Rotavirus Salmonella

Parasitic infections through food

Amoebiasis Anisakiasis Cryptosporidiosis Cyclosporiasis Diphyllobothriasis Enterobiasis Fasciolopsiasis Fasciolosis Giardiasis Gnathostomiasis Paragonimiasis Toxoplasmosis Trichinosis Trichuriasis

Pesticides

Chlorpyrifos DDT Lindane Malathion Methamidophos

Preservatives

Benzoic acid Ethylenediaminetetraacetic acid
Ethylenediaminetetraacetic acid
(EDTA) Sodium
Sodium
benzoate

Sugar
Sugar
substitutes

Acesulfame potassium Aspartame Saccharin Sodium
Sodium
cyclamate Sorbitol Sucralose

Toxins, poisons, environment pollution

Aflatoxin Arsenic contamination of groundwater Benzene
Benzene
in soft drinks Bisphenol A Dieldrin Diethylstilbestrol Dioxin Mycotoxins Nonylphenol Shellfish poisoning

Food contamination incidents

Devon colic Swill milk scandal 1858 Bradford sweets poisoning 1900 English beer poisoning Morinaga Milk arsenic poisoning incident Minamata disease 1971 Iraq poison grain disaster Toxic oil syndrome 1993 Jack in the Box E. coli outbreak 1996 Odwalla E. coli outbreak 2006 North American E. coli outbreaks ICA meat repackaging controversy 2008 Canada listeriosis outbreak 2008 Chinese milk scandal 2008 Irish pork crisis 2008 United States salmonellosis outbreak 2011 Germany E. coli outbreak 2011 Taiwan food scandal 2011 United States listeriosis outbreak 2013 Bihar school meal poisoning 2013 horse meat scandal 2013 Taiwan food scandal 2014 Taiwan food scandal 2017 Brazil weak meat scandal 2017–18 South African listeriosis outbreak Food safety
Food safety
incidents in China Foodborne illness

outbreaks death toll United States

Regulation, standards, watchdogs

Acceptable daily intake E number Food labeling regulations Food libel laws International Food Safety Network ISO 22000 Quality Assurance International

Institutions

Centre for Food Safety European Food Safety Authority Institute for Food Safety and Health International Food Safety Network Ministry of Food and Drug
Drug
Safety

v t e

Food substitutes

Artificial fat substitutes

Olestra Trans fat

Artificial protein substitutes

Acid-hydrolyzed vegetable protein

Artificial sugar substitutes

Acesulfame potassium Alitame Aspartame Aspartame-acesulfame salt Dulcin Glucin Hydrogenated starch hydrolysates Neohesperidin dihydrochalcone Neotame NutraSweet Nutrinova Saccharin Sodium
Sodium
cyclamate Sucralose

Natural food substitutes

Cheese analogues Coffee substitutes Egg substitutes Meat analogues

bacon list

Milk substitutes Phyllodulcin Salt substitutes

Food politics

Food power Food security Famine Malnutrition Overnutrition

Institutions

International Association for Food Protection Food and Drug
Drug
Administration Food and Agriculture Organization National Agriculture and Food Research Organization National Food and Drug
Drug
Authority

v t e

Diving medicine, physiology, physics and environment

Diving medicine

Injuries and disorders

Pressure

Oxygen

Freediving blackout Hyperoxia Hypoxia (medical) Oxygen
Oxygen
toxicity

Inert gases

Atrial septal defect Avascular necrosis Decompression sickness Dysbaric osteonecrosis High-pressure nervous syndrome Hydrogen
Hydrogen
narcosis Isobaric counterdiffusion Nitrogen
Nitrogen
narcosis Taravana Uncontrolled decompression

Carbon
Carbon
dioxide

Hypercapnia Hypocapnia

Aerosinusitis Air embolism Alternobaric vertigo Barodontalgia Barostriction Barotrauma Compression arthralgia Decompression illness Dental barotrauma Dysbarism Ear clearing Frenzel maneuver Valsalva maneuver

Immersion

Asphyxia Drowning Hypothermia Immersion diuresis Instinctive drowning response Laryngospasm Salt water aspiration syndrome Swimming-induced pulmonary edema

List of signs and symptoms of diving disorders Cramps Diving disorders Motion sickness Surfer's ear

Treatments

Diving chamber Diving medicine Hyperbaric medicine Hyperbaric treatment schedules In-water recompression Oxygen
Oxygen
therapy

Fitness to dive

Diving physiology

Artificial gills (human) Blood–air barrier Blood shift Breathing Circulatory system CO₂ retention Cold shock response Dead space (physiology) Decompression (diving) Decompression theory Diving reflex Gas exchange History of decompression research and development Lipid Maximum operating depth Metabolism Normocapnia Oxygen
Oxygen
window in diving decompression Perfusion Physiological response to water immersion Physiology of decompression Pulmonary circulation Respiratory exchange ratio Respiratory quotient Respiratory system Systemic circulation Tissue (biology)

Diving physics

Ambient pressure Amontons' law Anti-fog Archimedes' principle Atmospheric pressure Boyle's law Breathing
Breathing
performance of regulators Buoyancy Charles's law Combined gas law Dalton's law Diffusion Force Gay-Lussac's law Henry's law Hydrophobe Hydrostatic pressure Ideal gas law Molecular diffusion Neutral buoyancy Oxygen
Oxygen
fraction Partial pressure Permeation Pressure Psychrometric constant Snell's law Solubility Solution Supersaturation Surface tension Surfactant Torricellian chamber Underwater vision Weight

Diving environment

Algal bloom Breaking wave Ocean current Current (stream) Ekman transport Halocline List of diving hazards and precautions Longshore drift Rip current Stratification Surf Surge (wave action) Thermocline Tides Turbidity Undertow (water waves) Upwelling

Researchers in diving medicine and physiology

Arthur J. Bachrach Albert R. Behnke Paul Bert George F. Bond Robert Boyle Albert A. Bühlmann John R Clarke William Paul Fife John Scott Haldane Robert William Hamilton Jr. Leonard Erskine Hill Brian Andrew Hills Felix Hoppe-Seyler Christian J. Lambertsen Simon Mitchell Charles Momsen John Rawlins R.N. Charles Wesley Shilling Edward D. Thalmann Jules Triger

Diving medical research organisations

Aerospace Medical Association Divers Alert Network
Divers Alert Network
(DAN) Diving Diseases Research Centre
Diving Diseases Research Centre
(DDRC) Diving Medical Advisory Council (DMAC European Diving Technology Committee
European Diving Technology Committee
(EDTC) European Underwater and Baromedical Society
European Underwater and Baromedical Society
(EUBS) National Board of Diving and Hyperbaric Medical Technology Naval Submarine Medical Research Laboratory Royal Australian Navy School of Underwater Medicine Rubicon Foundation South Pacific Underwater Medicine Society
South Pacific Underwater Medicine Society
(SPUMS) Southern African Underwater and Hyperbaric Medical Association
Southern African Underwater and Hyperbaric Medical Association
(SAUHMA

Undersea and Hyperbaric Medical Society
Undersea and Hyperbaric Medical Society
(UHMS) United States Navy Experimental Diving Unit
United States Navy Experimental Diving Unit
(NEDU)

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