Metabolism

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"Cell metabolism" redirects here. Metabolism_sentence_0

For the journal, see Cell Metabolism. Metabolism_sentence_1

For the architectural movement, see Metabolism (architecture). Metabolism_sentence_2

Metabolism (/məˈtæbəlɪzəm/, from Greek: μεταβολή metabolē, "change") is the set of life-sustaining chemical reactions in organisms. Metabolism_sentence_3

The three main purposes of metabolism are: the conversion of food 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 metabolic wastes. Metabolism_sentence_4

These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism_sentence_5

(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 above described set of reactions within the cells is called intermediary metabolism or intermediate metabolism). Metabolism_sentence_6

Metabolic reactions may be categorized as catabolic – the breaking down of compounds (for example, the breaking down of glucose to pyruvate by cellular respiration); or anabolic – the building up (synthesis) of compounds (such as proteins, carbohydrates, lipids, and nucleic acids). Metabolism_sentence_7

Usually, catabolism releases energy, and anabolism consumes energy. Metabolism_sentence_8

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. Metabolism_sentence_9

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. Metabolism_sentence_10

Enzymes act as catalysts – 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 signals from other cells. Metabolism_sentence_11

The metabolic system of a particular organism determines which substances it will find nutritious and which poisonous. Metabolism_sentence_12

For example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals. Metabolism_sentence_13

The basal metabolic rate of an organism is the measure of the amount of energy consumed by all of these chemical reactions. Metabolism_sentence_14

A striking feature of metabolism is the similarity of the basic metabolic pathways among vastly different species. Metabolism_sentence_15

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 and huge multicellular organisms like elephants. Metabolism_sentence_16

These similarities in metabolic pathways are likely due to their early appearance in evolutionary history, and their retention because of their efficacy. Metabolism_sentence_17

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. Metabolism_sentence_18

Key biochemicals Metabolism_section_0

Further information: Biomolecule, Cell (biology), and Biochemistry Metabolism_sentence_19

Most of the structures that make up animals, plants and microbes are made from four basic classes of molecule: amino acids, carbohydrates , nucleic acid and lipids (often called fats). Metabolism_sentence_20

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. Metabolism_sentence_21

These biochemicals can be joined together to make polymers such as DNA and proteins, essential macromolecules of life. Metabolism_sentence_22

Metabolism_table_general_0

Type of moleculeMetabolism_header_cell_0_0_0 Name of monomer formsMetabolism_header_cell_0_0_1 Name of polymer formsMetabolism_header_cell_0_0_2 Examples of polymer formsMetabolism_header_cell_0_0_3
Amino acidsMetabolism_cell_0_1_0 Amino acidsMetabolism_cell_0_1_1 Proteins (made of polypeptides)Metabolism_cell_0_1_2 Fibrous proteins and globular proteinsMetabolism_cell_0_1_3
CarbohydratesMetabolism_cell_0_2_0 MonosaccharidesMetabolism_cell_0_2_1 PolysaccharidesMetabolism_cell_0_2_2 Starch, glycogen and celluloseMetabolism_cell_0_2_3
Nucleic acidsMetabolism_cell_0_3_0 NucleotidesMetabolism_cell_0_3_1 PolynucleotidesMetabolism_cell_0_3_2 DNA and RNAMetabolism_cell_0_3_3

Amino acids and proteins Metabolism_section_1

Proteins are made of amino acids arranged in a linear chain joined together by peptide bonds. Metabolism_sentence_23

Many proteins are enzymes that catalyze the chemical reactions in metabolism. Metabolism_sentence_24

Other proteins have structural or mechanical functions, such as those that form the cytoskeleton, a system of scaffolding that maintains the cell shape. Metabolism_sentence_25

Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes, and the cell cycle. Metabolism_sentence_26

Amino acids also contribute to cellular energy metabolism by providing a carbon source for entry into the citric acid cycle (tricarboxylic acid cycle), especially when a primary source of energy, such as glucose, is scarce, or when cells undergo metabolic stress. Metabolism_sentence_27

Lipids Metabolism_section_2

Lipids are the most diverse group of biochemicals. Metabolism_sentence_28

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. Metabolism_sentence_29

Lipids are usually defined as hydrophobic or amphipathic biological molecules but will dissolve in organic solvents such as alcohol, benzene or chloroform. Metabolism_sentence_30

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. Metabolism_sentence_31

Several variations on this basic structure exist, including backbones such as sphingosine in the sphingomyelin, and hydrophilic groups such as phosphate as in phospholipids. Metabolism_sentence_32

Steroids such as sterol are another major class of lipids. Metabolism_sentence_33

Carbohydrates Metabolism_section_3

Carbohydrates are aldehydes or ketones, with many hydroxyl groups attached, that can exist as straight chains or rings. Metabolism_sentence_34

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). Metabolism_sentence_35

The basic carbohydrate units are called monosaccharides and include galactose, fructose, and most importantly glucose. Metabolism_sentence_36

Monosaccharides can be linked together to form polysaccharides in almost limitless ways. Metabolism_sentence_37

Nucleotides Metabolism_section_4

The two nucleic acids, DNA and RNA, are polymers of nucleotides. Metabolism_sentence_38

Each nucleotide is composed of a phosphate attached to a ribose or deoxyribose sugar group which is attached to a nitrogenous base. Metabolism_sentence_39

Nucleic acids are critical for the storage and use of genetic information, and its interpretation through the processes of transcription and protein biosynthesis. Metabolism_sentence_40

This information is protected by DNA repair mechanisms and propagated through DNA replication. Metabolism_sentence_41

Many viruses have an RNA genome, such as HIV, which uses reverse transcription to create a DNA template from its viral RNA genome. Metabolism_sentence_42

RNA in ribozymes such as spliceosomes and ribosomes is similar to enzymes as it can catalyze chemical reactions. Metabolism_sentence_43

Individual nucleosides are made by attaching a nucleobase to a ribose sugar. Metabolism_sentence_44

These bases are heterocyclic rings containing nitrogen, classified as purines or pyrimidines. Metabolism_sentence_45

Nucleotides also act as coenzymes in metabolic-group-transfer reactions. Metabolism_sentence_46

Coenzymes Metabolism_section_5

Main article: Coenzyme Metabolism_sentence_47

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. Metabolism_sentence_48

This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions. Metabolism_sentence_49

These group-transfer intermediates are called coenzymes. Metabolism_sentence_50

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. Metabolism_sentence_51

These coenzymes are therefore continuously made, consumed and then recycled. Metabolism_sentence_52

One central coenzyme is adenosine triphosphate (ATP), the universal energy currency of cells. Metabolism_sentence_53

This nucleotide is used to transfer chemical energy between different chemical reactions. Metabolism_sentence_54

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. Metabolism_sentence_55

ATP acts as a bridge between catabolism and anabolism. Metabolism_sentence_56

Catabolism breaks down molecules, and anabolism puts them together. Metabolism_sentence_57

Catabolic reactions generate ATP, and anabolic reactions consume it. Metabolism_sentence_58

It also serves as a carrier of phosphate groups in phosphorylation reactions. Metabolism_sentence_59

A vitamin is an organic compound needed in small quantities that cannot be made in cells. Metabolism_sentence_60

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. Metabolism_sentence_61

Nicotinamide adenine dinucleotide (NAD), a derivative of vitamin B3 (niacin), is an important coenzyme that acts as a hydrogen acceptor. Metabolism_sentence_62

Hundreds of separate types of dehydrogenases remove electrons from their substrates and reduce NAD into NADH. Metabolism_sentence_63

This reduced form of the coenzyme is then a substrate for any of the reductases in the cell that need to reduce their substrates. Metabolism_sentence_64

Nicotinamide adenine dinucleotide exists in two related forms in the cell, NADH and NADPH. Metabolism_sentence_65

The NAD/NADH form is more important in catabolic reactions, while NADP/NADPH is used in anabolic reactions. Metabolism_sentence_66

Mineral and cofactors Metabolism_section_6

Further information: Bioinorganic chemistry Metabolism_sentence_67

Inorganic elements play critical roles in metabolism; some are abundant (e.g. sodium and potassium) while others function at minute concentrations. Metabolism_sentence_68

About 99% of a human's body weight is made up of the elements carbon, nitrogen, calcium, sodium, chlorine, potassium, hydrogen, phosphorus, oxygen and sulfur. Metabolism_sentence_69

Organic compounds (proteins, lipids and carbohydrates) contain the majority of the carbon and nitrogen; most of the oxygen and hydrogen is present as water. Metabolism_sentence_70

The abundant inorganic elements act as electrolytes. Metabolism_sentence_71

The most important ions are sodium, potassium, calcium, magnesium, chloride, phosphate and the organic ion bicarbonate. Metabolism_sentence_72

The maintenance of precise ion gradients across cell membranes maintains osmotic pressure and pH. Metabolism_sentence_73

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. Metabolism_sentence_74

Electrolytes enter and leave cells through proteins in the cell membrane called ion channels. Metabolism_sentence_75

For example, muscle contraction depends upon the movement of calcium, sodium and potassium through ion channels in the cell membrane and T-tubules. Metabolism_sentence_76

Transition metals are usually present as trace elements in organisms, with zinc and iron being most abundant of those. Metabolism_sentence_77

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 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. Metabolism_sentence_78

Metal micronutrients are taken up into organisms by specific transporters and bind to storage proteins such as ferritin or metallothionein when not in use. Metabolism_sentence_79

Catabolism Metabolism_section_7

Catabolism is the set of metabolic processes that break down large molecules. Metabolism_sentence_80

These include breaking down and oxidizing food molecules. Metabolism_sentence_81

The purpose of the catabolic reactions is to provide the energy and components needed by anabolic reactions which build molecules. Metabolism_sentence_82

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. Metabolism_sentence_83

Organic molecules are used as a source of energy by organotrophs, while lithotrophs use inorganic substrates, and phototrophs capture sunlight as chemical energy. Metabolism_sentence_84

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. Metabolism_sentence_85

In animals, these reactions involve complex organic molecules that are broken down to simpler molecules, such as carbon dioxide and water. Metabolism_sentence_86

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. Metabolism_sentence_87

The most common set of catabolic reactions in animals can be separated into three main stages. Metabolism_sentence_88

In the first stage, large organic molecules, such as proteins, polysaccharides or lipids, are digested into their smaller components outside cells. Metabolism_sentence_89

Next, these smaller molecules are taken up by cells and converted to smaller molecules, usually acetyl coenzyme A (acetyl-CoA), which releases some energy. Metabolism_sentence_90

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. Metabolism_sentence_91

Digestion Metabolism_section_8

Further information: Digestion and Gastrointestinal tract Metabolism_sentence_92

Macromolecules cannot be directly processed by cells. Metabolism_sentence_93

Macromolecules must be broken into smaller units before they can be used in cell metabolism. Metabolism_sentence_94

Different classes of enzymes were being used to digest these polymers. Metabolism_sentence_95

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 Metabolism_sentence_96

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 salivary glands. Metabolism_sentence_97

The amino acids or sugars released by these extracellular enzymes are then pumped into cells by active transport proteins. Metabolism_sentence_98

Energy from organic compounds Metabolism_section_9

Further information: Cellular respiration, Fermentation (biochemistry), Carbohydrate catabolism, Fat catabolism, and Protein catabolism Metabolism_sentence_99

Carbohydrate catabolism is the breakdown of carbohydrates into smaller units. Metabolism_sentence_100

Carbohydrates are usually taken into cells once they have been digested into monosaccharides. Metabolism_sentence_101

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. Metabolism_sentence_102

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. Metabolism_sentence_103

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. Metabolism_sentence_104

This oxidation releases carbon dioxide as a waste product. Metabolism_sentence_105

In anaerobic conditions, glycolysis produces lactate, through the enzyme lactate dehydrogenase re-oxidizing NADH to NAD+ for re-use in glycolysis. Metabolism_sentence_106

An alternative route for glucose breakdown is the pentose phosphate pathway, which reduces the coenzyme NADPH and produces pentose sugars such as ribose, the sugar component of nucleic acids. Metabolism_sentence_107

Fats are catabolised by hydrolysis to free fatty acids and glycerol. Metabolism_sentence_108

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. Metabolism_sentence_109

Fatty acids release more energy upon oxidation than carbohydrates because carbohydrates contain more oxygen in their structures. Metabolism_sentence_110

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. Metabolism_sentence_111

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. Metabolism_sentence_112

Amino acids are either used to synthesize proteins and other biomolecules, or oxidized to urea and carbon dioxide as a source of energy. Metabolism_sentence_113

The oxidation pathway starts with the removal of the amino group by a transaminase. Metabolism_sentence_114

The amino group is fed into the urea cycle, leaving a deaminated carbon skeleton in the form of a keto acid. Metabolism_sentence_115

Several of these keto acids are intermediates in the citric acid cycle, for example the deamination of glutamate forms α-ketoglutarate. Metabolism_sentence_116

The glucogenic amino acids can also be converted into glucose, through gluconeogenesis (discussed below). Metabolism_sentence_117

Energy transformations Metabolism_section_10

Oxidative phosphorylation Metabolism_section_11

Further information: Oxidative phosphorylation, Chemiosmosis, and Mitochondrion Metabolism_sentence_118

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. Metabolism_sentence_119

This is done in eukaryotes by a series of proteins in the membranes of mitochondria called the electron transport chain. Metabolism_sentence_120

In prokaryotes, these proteins are found in the cell's inner membrane. Metabolism_sentence_121

These proteins use the energy released from passing electrons from reduced molecules like NADH onto oxygen to pump protons across a membrane. Metabolism_sentence_122

Pumping protons out of the mitochondria creates a proton concentration difference across the membrane and generates an electrochemical gradient. Metabolism_sentence_123

This force drives protons back into the mitochondrion through the base of an enzyme called ATP synthase. Metabolism_sentence_124

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. Metabolism_sentence_125

Energy from inorganic compounds Metabolism_section_12

Further information: Microbial metabolism and Nitrogen cycle Metabolism_sentence_126

Chemolithotrophy is a type of metabolism found in prokaryotes where energy is obtained from the oxidation of inorganic compounds. Metabolism_sentence_127

These organisms can use hydrogen, reduced sulfur compounds (such as sulfide, hydrogen sulfide and thiosulfate), ferrous iron (FeII) or ammonia as sources of reducing power and they gain energy from the oxidation of these compounds with electron acceptors such as oxygen or nitrite. Metabolism_sentence_128

These microbial processes are important in global biogeochemical cycles such as acetogenesis, nitrification and denitrification and are critical for soil fertility. Metabolism_sentence_129

Energy from light Metabolism_section_13

Further information: Phototroph, Photophosphorylation, and Chloroplast Metabolism_sentence_130

The energy in sunlight is captured by plants, cyanobacteria, purple bacteria, green sulfur bacteria and some protists. Metabolism_sentence_131

This process is often coupled to the conversion of carbon dioxide into organic compounds, as part of photosynthesis, which is discussed below. Metabolism_sentence_132

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. Metabolism_sentence_133

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. Metabolism_sentence_134

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. Metabolism_sentence_135

Reaction centers are classed 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. Metabolism_sentence_136

In plants, algae, and cyanobacteria, photosystem II uses light energy to remove electrons from water, releasing oxygen as a waste product. Metabolism_sentence_137

The electrons then flow to the cytochrome b6f complex, which uses their energy to pump protons across the thylakoid membrane in the chloroplast. Metabolism_sentence_138

These protons move back through the membrane as they drive the ATP synthase, as before. Metabolism_sentence_139

The electrons then flow through photosystem I and can then either be used to reduce the coenzyme NADPfThese cooenzyme can be used in the Calvin cycle, which is discussed below, or recycled for further ATP generation. Metabolism_sentence_140

Anabolism Metabolism_section_14

Further information: Anabolism Metabolism_sentence_141

Anabolism is the set of constructive metabolic processes where the energy released by catabolism is used to synthesize complex molecules. Metabolism_sentence_142

In general, the complex molecules that make up cellular structures are constructed step-by-step from small and simple precursors. Metabolism_sentence_143

Anabolism involves three basic stages. Metabolism_sentence_144

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. Metabolism_sentence_145

Anabolism in organisms can be different according to the source of constructed molecules in their cells. Metabolism_sentence_146

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. Metabolism_sentence_147

Heterotrophs, on the other hand, require a source of more complex substances, such as monosaccharides and amino acids, to produce these complex molecules. Metabolism_sentence_148

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. Metabolism_sentence_149

Carbon fixation Metabolism_section_15

Further information: Photosynthesis, Carbon fixation, and Chemosynthesis Metabolism_sentence_150

Photosynthesis is the synthesis of carbohydrates from sunlight and carbon dioxide (CO2). Metabolism_sentence_151

In plants, cyanobacteria and algae, oxygenic photosynthesis splits water, with oxygen produced as a waste product. Metabolism_sentence_152

This process uses the ATP and NADPH produced by the photosynthetic reaction centres, as described above, to convert CO2 into glycerate 3-phosphate, which can then be converted into glucose. Metabolism_sentence_153

This carbon-fixation reaction is carried out by the enzyme RuBisCO as part of the Calvin – Benson cycle. Metabolism_sentence_154

Three types of photosynthesis occur in plants, C3 carbon fixation, C4 carbon fixation and CAM photosynthesis. Metabolism_sentence_155

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. Metabolism_sentence_156

In photosynthetic prokaryotes the mechanisms of carbon fixation are more diverse. Metabolism_sentence_157

Here, carbon dioxide can be fixed by the Calvin – Benson cycle, a reversed citric acid cycle, or the carboxylation of acetyl-CoA. Metabolism_sentence_158

Prokaryotic chemoautotrophs also fix CO2 through the Calvin–Benson cycle, but use energy from inorganic compounds to drive the reaction. Metabolism_sentence_159

Carbohydrates and glycans Metabolism_section_16

Further information: Gluconeogenesis, Glyoxylate cycle, Glycogenesis, and Glycosylation Metabolism_sentence_160

In carbohydrate anabolism, simple organic acids can be converted into monosaccharides such as glucose and then used to assemble polysaccharides such as starch. Metabolism_sentence_161

The generation of glucose from compounds like pyruvate, lactate, glycerol, glycerate 3-phosphate and amino acids is called gluconeogenesis. Metabolism_sentence_162

Gluconeogenesis converts pyruvate to glucose-6-phosphate through a series of intermediates, many of which are shared with glycolysis. Metabolism_sentence_163

However, this pathway is not simply glycolysis run in reverse, as several steps are catalyzed by non-glycolytic enzymes. Metabolism_sentence_164

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. Metabolism_sentence_165

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. Metabolism_sentence_166

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. Metabolism_sentence_167

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. Metabolism_sentence_168

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. Metabolism_sentence_169

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-Glc) to an acceptor hydroxyl group on the growing polysaccharide. Metabolism_sentence_170

As any of the hydroxyl groups on the ring of the substrate can be acceptors, the polysaccharides produced can have straight or branched structures. Metabolism_sentence_171

The polysaccharides produced can have structural or metabolic functions themselves, or be transferred to lipids and proteins by enzymes called oligosaccharyltransferases. Metabolism_sentence_172

Fatty acids, isoprenoids and sterol Metabolism_section_17

Further information: Fatty acid synthesis and Steroid metabolism Metabolism_sentence_173

Fatty acids are made by fatty acid synthases that polymerize and then reduce acetyl-CoA units. Metabolism_sentence_174

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. Metabolism_sentence_175

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, while in plant plastids and bacteria separate type II enzymes perform each step in the pathway. Metabolism_sentence_176

Terpenes and isoprenoids are a large class of lipids that include the carotenoids and form the largest class of plant natural products. Metabolism_sentence_177

These compounds are made by the assembly and modification of isoprene units donated from the reactive precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate. Metabolism_sentence_178

These precursors can be made in different ways. Metabolism_sentence_179

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. Metabolism_sentence_180

One important reaction that uses these activated isoprene donors is sterol biosynthesis. Metabolism_sentence_181

Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol. Metabolism_sentence_182

Lanosterol can then be converted into other sterol such as cholesterol and ergosterol. Metabolism_sentence_183

Proteins Metabolism_section_18

Further information: Protein biosynthesis and Amino acid synthesis Metabolism_sentence_184

Organisms vary in their ability to synthesize the 20 common amino acids. Metabolism_sentence_185

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. Metabolism_sentence_186

Some simple parasites, such as the bacteria Mycoplasma pneumoniae, lack all amino acid synthesis and take their amino acids directly from their hosts. Metabolism_sentence_187

All amino acids are synthesized from intermediates in glycolysis, the citric acid cycle, or the pentose phosphate pathway. Metabolism_sentence_188

Nitrogen is provided by glutamate and glutamine. Metabolism_sentence_189

Nonessensial amino acid synthesis depends on the formation of the appropriate alpha-keto acid, which is then transaminated to form an amino acid. Metabolism_sentence_190

Amino acids are made into proteins by being joined together in a chain of peptide bonds. Metabolism_sentence_191

Each different protein has a unique sequence of amino acid residues: this is its primary structure. Metabolism_sentence_192

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. Metabolism_sentence_193

Proteins are made from amino acids that have been activated by attachment to a transfer RNA molecule through an ester bond. Metabolism_sentence_194

This aminoacyl-tRNA precursor is produced in an ATP-dependent reaction carried out by an aminoacyl tRNA synthetase. Metabolism_sentence_195

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. Metabolism_sentence_196

Nucleotide synthesis and salvage Metabolism_section_19

Further information: Nucleotide salvage, Pyrimidine biosynthesis, and Purine § Metabolism Metabolism_sentence_197

Nucleotides are made from amino acids, carbon dioxide and formic acid in pathways that require large amounts of metabolic energy. Metabolism_sentence_198

Consequently, most organisms have efficient systems to salvage preformed nucleotides. Metabolism_sentence_199

Purines are synthesized as nucleosides (bases attached to ribose). Metabolism_sentence_200

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. Metabolism_sentence_201

Pyrimidines, on the other hand, are synthesized from the base orotate, which is formed from glutamine and aspartate. Metabolism_sentence_202

Xenobiotics and redox metabolism Metabolism_section_20

Further information: Xenobiotic metabolism, Drug metabolism, Alcohol metabolism, and Antioxidant Metabolism_sentence_203

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. Metabolism_sentence_204

These potentially damaging compounds are called xenobiotics. Metabolism_sentence_205

Xenobiotics such as synthetic drugs, natural poisons and antibiotics are detoxified by a set of xenobiotic-metabolizing enzymes. Metabolism_sentence_206

In humans, these include cytochrome P450 oxidases, UDP-glucuronosyltransferases, and glutathione S-transferases. Metabolism_sentence_207

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). Metabolism_sentence_208

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). Metabolism_sentence_209

In ecology, these reactions are particularly important in microbial biodegradation of pollutants and the bioremediation of contaminated land and oil spills. Metabolism_sentence_210

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. Metabolism_sentence_211

A related problem for aerobic organisms is oxidative stress. Metabolism_sentence_212

Here, processes including oxidative phosphorylation and the formation of disulfide bonds during protein folding produce reactive oxygen species such as hydrogen peroxide. Metabolism_sentence_213

These damaging oxidants are removed by antioxidant metabolites such as glutathione and enzymes such as catalases and peroxidases. Metabolism_sentence_214

Thermodynamics of living organisms Metabolism_section_21

Further information: Biological thermodynamics Metabolism_sentence_215

Living organisms must obey the laws of thermodynamics, which describe the transfer of heat and work. Metabolism_sentence_216

The second law of thermodynamics states that in any closed system, the amount of entropy (disorder) cannot decrease. Metabolism_sentence_217

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. Metabolism_sentence_218

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. Metabolism_sentence_219

The metabolism of a cell achieves this by coupling the spontaneous processes of catabolism to the non-spontaneous processes of anabolism. Metabolism_sentence_220

In thermodynamic terms, metabolism maintains order by creating disorder. Metabolism_sentence_221

Regulation and control Metabolism_section_22

Further information: Metabolic pathway, Metabolic control analysis, Hormone, Regulatory enzymes, and Cell signaling Metabolism_sentence_222

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. Metabolism_sentence_223

Metabolic regulation also allows organisms to respond to signals and interact actively with their environments. Metabolism_sentence_224

Two closely linked concepts are important for understanding how metabolic pathways are controlled. Metabolism_sentence_225

Firstly, the regulation of an enzyme in a pathway is how its activity is increased and decreased in response to signals. Metabolism_sentence_226

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). Metabolism_sentence_227

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. Metabolism_sentence_228

There are multiple levels of metabolic regulation. Metabolism_sentence_229

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. Metabolism_sentence_230

This type of regulation often involves allosteric regulation of the activities of multiple enzymes in the pathway. Metabolism_sentence_231

Extrinsic control involves a cell in a multicellular organism changing its metabolism in response to signals from other cells. Metabolism_sentence_232

These signals are usually in the form of water soluble messengers such as hormones and growth factors and are detected by specific receptors on the cell surface. Metabolism_sentence_233

These signals are then transmitted inside the cell by second messenger systems that often involved the phosphorylation of proteins. Metabolism_sentence_234

A very well understood example of extrinsic control is the regulation of glucose metabolism by the hormone insulin. Metabolism_sentence_235

Insulin is produced in response to rises in blood glucose levels. Metabolism_sentence_236

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. Metabolism_sentence_237

The metabolism of glycogen is controlled by activity of phosphorylase, the enzyme that breaks down glycogen, and glycogen synthase, the enzyme that makes it. Metabolism_sentence_238

These enzymes are regulated in a reciprocal fashion, with phosphorylation inhibiting glycogen synthase, but activating phosphorylase. Metabolism_sentence_239

Insulin causes glycogen synthesis by activating protein phosphatases and producing a decrease in the phosphorylation of these enzymes. Metabolism_sentence_240

Evolution Metabolism_section_23

Further information: Molecular evolution and Phylogenetics Metabolism_sentence_241

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. Metabolism_sentence_242

This universal ancestral cell was prokaryotic and probably a methanogen that had extensive amino acid, nucleotide, carbohydrate and lipid metabolism. Metabolism_sentence_243

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. Metabolism_sentence_244

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 world. Metabolism_sentence_245

Many models have been proposed to describe the mechanisms by which novel metabolic pathways evolve. Metabolism_sentence_246

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. Metabolism_sentence_247

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. Metabolism_sentence_248

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. Metabolism_sentence_249

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. Metabolism_sentence_250

As well as the evolution of new metabolic pathways, evolution can also cause the loss of metabolic functions. Metabolism_sentence_251

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. Metabolism_sentence_252

Similar reduced metabolic capabilities are seen in endosymbiotic organisms. Metabolism_sentence_253

Investigation and manipulation Metabolism_section_24

Further information: Protein methods, Proteomics, Metabolomics, and Metabolic network modelling Metabolism_sentence_254

Classically, metabolism is studied by a reductionist approach that focuses on a single metabolic pathway. Metabolism_sentence_255

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. Metabolism_sentence_256

The enzymes that catalyze these chemical reactions can then be purified and their kinetics and responses to inhibitors investigated. Metabolism_sentence_257

A parallel approach is to identify the small molecules in a cell or tissue; the complete set of these molecules is called the metabolome. Metabolism_sentence_258

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. Metabolism_sentence_259

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. Metabolism_sentence_260

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. Metabolism_sentence_261

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 microarray studies. Metabolism_sentence_262

Using these techniques, a model of human metabolism has now been produced, which will guide future drug discovery and biochemical research. Metabolism_sentence_263

These models are now used in network analysis, to classify human diseases into groups that share common proteins or metabolites. Metabolism_sentence_264

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. Metabolism_sentence_265

A major technological application of this information is metabolic engineering. Metabolism_sentence_266

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. Metabolism_sentence_267

These genetic modifications usually aim to reduce the amount of energy used to produce the product, increase yields and reduce the production of wastes. Metabolism_sentence_268

History Metabolism_section_25

Further information: History of biochemistry and History of molecular biology Metabolism_sentence_269

The term metabolism is derived from French "métabolisme" or Ancient Greek μεταβολή – "Metabole" for "a change" which derived from μεταβάλλ –"Metaballein" means "To change" Metabolism_sentence_270

Greek philosophy Metabolism_section_26

Aristotle's The Parts of Animals sets out enough details of his views on metabolism for an open flow model to be made. Metabolism_sentence_271

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. Metabolism_sentence_272

Islamic medicine Metabolism_section_27

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." Metabolism_sentence_273

Application of the scientific method Metabolism_section_28

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. Metabolism_sentence_274

The first controlled experiments in human metabolism were published by Santorio Santorio in 1614 in his book Ars de statica medicina. Metabolism_sentence_275

He described how he weighed himself before and after eating, sleep, working, sex, fasting, drinking, and excreting. Metabolism_sentence_276

He found that most of the food he took in was lost through what he called "insensible perspiration". Metabolism_sentence_277

In these early studies, the mechanisms of these metabolic processes had not been identified and a vital force was thought to animate living tissue. Metabolism_sentence_278

In the 19th century, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur concluded that fermentation was catalyzed by substances within the yeast cells he called "ferments". Metabolism_sentence_279

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." Metabolism_sentence_280

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. Metabolism_sentence_281

This proved that the organic compounds and chemical reactions found in cells were no different in principle than any other part of chemistry. Metabolism_sentence_282

It was the discovery of enzymes 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. Metabolism_sentence_283

The mass of biochemical knowledge grew rapidly throughout the early 20th century. Metabolism_sentence_284

One of the most prolific of these modern biochemists was Hans Krebs who made huge contributions to the study of metabolism. Metabolism_sentence_285

He discovered the urea cycle and later, working with Hans Kornberg, the citric acid cycle and the glyoxylate cycle. Metabolism_sentence_286

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. Metabolism_sentence_287

These techniques have allowed the discovery and detailed analysis of the many molecules and metabolic pathways in cells. Metabolism_sentence_288

See also Metabolism_section_29

Metabolism_unordered_list_0


Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Metabolism.