Metabolism

Structure of the coenzyme adenosine triphosphate, a central intermediate in energy metabolism.

Metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down large molecules, for example to harvest energy in cellular respiration. Anabolism, on the other hand, uses energy to construct components of cells such as proteins and nucleic acids.

The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed into another by a sequence of enzymes. Enzymes are crucial to metabolism because they allow organisms to drive desirable but thermodynamically unfavorable reactions by coupling them to favorable ones. Enzymes also allow the regulation of metabolic pathways in response to changes in the cell\'s environment or signals from other cells.

The metabolism of an organism determines which substances it will find nutritious and which it will find poisonous. For example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals.Friedrich C (1998). "Physiology and genetics of sulfur-oxidizing bacteria". Adv Microb Physiol 39: 235-89. PMID 9328649.  The speed of metabolism, the metabolic rate, also influences how much food an organism will require.

A striking feature of metabolism is the similarity of the basic metabolic pathways between even vastly different species. For example, the set of carboxylic acids that are best known as the intermediates in the citric acid cycle are present in all organisms, being found in species as diverse as the unicellular bacteria Escherichia coli and huge multicellular organisms like elephants.Smith E, Morowitz H (2004). "Universality in intermediary metabolism". Proc Natl Acad Sci U S A 101 (36): 13168-73. PMID 15340153.  These striking similarities in metabolism are most likely the result of the high efficiency of these pathways, and of their early appearance in evolutionary history.Ebenhöh O, Heinrich R (2001). "Evolutionary optimization of metabolic pathways. Theoretical reconstruction of the stoichiometry of ATP and NADH producing systems". Bull Math Biol 63 (1): 21–55. PMID 11146883. Meléndez-Hevia E, Waddell T, Cascante M (1996). "The puzzle of the Krebs citric acid cycle: assembling the pieces of chemically feasible reactions, and opportunism in the design of metabolic pathways during evolution". J Mol Evol 43 (3): 293–303. PMID 8703096. 

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 from organic compounds 3 Energy transformations 3.1 Oxidative phosphorylation 3.2 Energy from inorganic compounds 3.3 Energy from light 4 Anabolism 4.1 Carbon fixation 4.2 Carbohydrates and glycans 4.3 Fatty acids, isoprenoids and steroids 4.4 Proteins 4.5 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

Further information: Biomolecule, cell (biology) and biochemistry

Structure of a triacylglycerol lipid.

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, metabolism focuses on making these molecules, in the construction of cells and tissues, or breaking them down and using them as a source of energy, in the digestion and use of food. Many important biochemicals can be joined together to make polymers such as DNA and proteins. These macromolecules are essential parts of all living organisms. Some of the most common biological polymers are listed in the table below.

Type of molecule	Name of monomer forms	Name of polymer forms	Examples of polymer forms
Amino acids	Amino acids	Proteins (also called polypeptides)	Fibrous proteins and globular proteins
Carbohydrates	Monosaccharides	Polysaccharides	Starch, glycogen and cellulose
Nucleic acids	Nucleotides	Polynucleotides	DNA and RNA

Amino acids and proteins

Proteins are made of amino acids arranged in a linear chain and joined together by peptide bonds. Many proteins are the enzymes that catalyze the chemical reactions in metabolism. Other proteins have structural or mechanical functions, such as the proteins that form the cytoskeleton, a system of scaffolding that maintains the cell shape.Michie K, Löwe J (2006). "Dynamic filaments of the bacterial cytoskeleton". Annu Rev Biochem 75: 467-92. PMID 16756499.  Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes and the cell cycle.Nelson, David L.; Michael M. Cox (2005). Lehninger Principles of Biochemistry. New York: W. H. Freeman and company, 841. ISBN 0-7167-4339-6. 

Lipids

Lipids are the most diverse group of biochemicals. Their main structural uses are as part of biological membranes such as the cell membrane, or as a source of energy. Lipids are usually defined as hydrophobic or amphipathic biological molecules that will dissolve in organic solvents such as benzene or chloroform.Fahy E, Subramaniam S, Brown H, Glass C, Merrill A, Murphy R, Raetz C, Russell D, Seyama Y, Shaw W, Shimizu T, Spener F, van Meer G, VanNieuwenhze M, White S, Witztum J, Dennis E (2005). "A comprehensive classification system for lipids". J Lipid Res 46 (5): 839-61. PMID 15722563.  The fats are a large group of compounds that contain fatty acids and glycerol; a glycerol molecule attached to three fatty acid esters is a triacylglyceride.Nomenclature of Lipids. IUPAC-IUB Commission on Biochemical Nomenclature (CBN). Retrieved on 2007-03-08. Several variations on this basic structure exist, including alternate backbones such as sphingosine in the sphingolipids, and hydrophilic groups such as phosphate in phospholipids. Steroids such as cholesterol are another major class of lipids that are made in cells.Hegardt F (1999). "Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase: a control enzyme in ketogenesis". Biochem J 338 (Pt 3): 569-82. PMID 10051425. 

Carbohydrates

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

Carbohydrates are straight-chain aldehydes or ketones with many hydroxyl groups 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). The basic carbohydrate units are called monosaccharides and include galactose, fructose, and most importantly glucose. Monosaccharides can be linked together to form polysaccharides in almost limitless ways.Raman R, Raguram S, Venkataraman G, Paulson J, Sasisekharan R (2005). "Glycomics: an integrated systems approach to structure-function relationships of glycans". Nat Methods 2 (11): 817-24. PMID 16278650. 

Nucleotides

The polymers DNA and RNA are long chains of nucleotides. These molecules are critical for the storage and use of genetic information, through the processes of transcription and protein biosynthesis. This information is protected by DNA repair mechanisms and propagated through DNA replication. A few viruses have an RNA genome, for example HIV, which uses reverse transcription to create a DNA template from its viral RNA genome.Sierra S, Kupfer B, Kaiser R (2005). "Basics of the virology of HIV-1 and its replication". J Clin Virol 34 (4): 233-44. PMID 16198625.  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.Wimmer M, Rose I (1978). "Mechanisms of enzyme-catalyzed group transfer reactions". Annu Rev Biochem 47: 1031–78. PMID 354490. 

Coenzymes

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

Further information: Coenzyme

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.Mitchell P (1979). "The Ninth Sir Hans Krebs Lecture. Compartmentation and communication in living systems. Ligand conduction: a general catalytic principle in chemical, osmotic and chemiosmotic reaction systems". Eur J Biochem 95 (1): 1–20. PMID 378655.  This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions. These group-transfer intermediates are called coenzymes. Each class of group-transfer reaction 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 being made, consumed and then recycled.Dimroth P, von Ballmoos C, Meier T (2006). "Catalytic and mechanical cycles in F-ATP synthases. Fourth in the Cycles Review Series". EMBO Rep 7 (3): 276-82. PMID 16607397. 

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. ATP acts as a bridge between catabolism and anabolism, with catabolic reactions generating ATP and anabolic reactions consuming 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 the 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.Coulston, Ann; Kerner, John & Hattner, JoAnn et al. (2006), "Nutrition Principles and Clinical Nutrition", Stanford School of Medicine Nutrition Courses, SUMMIT Nicotinamide adenine dinucleotide (NADH), 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.Pollak N, Dölle C, Ziegler M (2007). "The power to reduce: pyridine nucleotides—small molecules with a multitude of functions". Biochem J 402 (2): 205-18. PMID 17295611.  Nicotinamide adenine dinucleotide exists in two related forms in the cell, NADH and NADPH. The NAD⁺/NADH form is more important in catabolic reactions, while NADP⁺/NADPH is used in anabolic reactions.

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

Further information: Physiology, bioinorganic chemistry, cofactor and iron metabolism

Inorganic elements play critical roles in metabolism; some are abundant (e.g. sodium and potassium) while others function at minute concentrations. About 99% of mammals\' mass are the elements carbon, nitrogen, calcium, sodium, chlorine, potassium, hydrogen, phosphorus, oxygen and sulfur.Heymsfield S, Waki M, Kehayias J, Lichtman S, Dilmanian F, Kamen Y, Wang J, Pierson R (1991). "Chemical and elemental analysis of humans in vivo using improved body composition models". Am J Physiol 261 (2 Pt 1): E190-8. PMID 1872381.  The organic compounds (proteins, lipids and carbohydrates) contain the majority of the carbon and nitrogen and most of the oxygen and hydrogen is present as water.

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 gradients across cell membranes maintains osmotic pressure and pH.Sychrová H (2004). "Yeast as a model organism to study transport and homeostasis of alkali metal cations". Physiol Res 53 Suppl 1: S91-8. PMID 15119939.  Ions are also critical for nerves and muscles, as action potentials in these tissues are produced by the exchange of electrolytes between the extracellular fluid and the cytosol.Levitan I (1988). "Modulation of ion channels in neurons and other cells". Annu Rev Neurosci 11: 119-36. PMID 2452594.  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.Dulhunty A (2006). "Excitation-contraction coupling from the 1950s into the new millennium". Clin Exp Pharmacol Physiol 33 (9): 763-72. PMID 16922804. 

The transition metals are usually present as trace elements in organisms, with zinc and iron being most abundant.Mahan D, Shields R (1998). "Macro- and micromineral composition of pigs from birth to 145 kilograms of body weight". J Anim Sci 76 (2): 506-12. PMID 9498359. Husted S, Mikkelsen B, Jensen J, Nielsen N (2004). "Elemental fingerprint analysis of barley (Hordeum vulgare) using inductively coupled plasma mass spectrometry, isotope-ratio mass spectrometry, and multivariate statistics". Anal Bioanal Chem 378 (1): 171-82. PMID 14551660.  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.Finney L, O\'Halloran T (2003). "Transition metal speciation in the cell: insights from the chemistry of metal ion receptors". Science 300 (5621): 931-6. PMID 12738850.  These cofactors are bound tightly to a specific protein; although enzyme cofactors can be modified during catalysis, cofactors always return to their original state after catalysis has taken place. The metal micronutrients are taken up into organisms by specific transporters and bound to storage proteins such as ferritin or metallothionein when not being used.Cousins R, Liuzzi J, Lichten L (2006). "Mammalian zinc transport, trafficking, and signals". J Biol Chem 281 (34): 24085-9. PMID 16793761. Dunn L, Rahmanto Y, Richardson D (2007). "Iron uptake and metabolism in the new millennium". Trends Cell Biol 17 (2): 93–100. PMID 17194590. 

Catabolism

Further information: Catabolism

Catabolism is the set of metabolic processes that break down large molecules. These include breaking down and oxidising food molecules. The purpose of the catabolic reactions is to provide the energy and components needed by anabolic reactions. The exact nature of these catabolic reactions differ from organism to organism, with organic molecules being used as a source of energy in 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 sulphate.Nealson K, Conrad P (1999). "Life: past, present and future". Philos Trans R Soc Lond B Biol Sci 354 (1392): 1923–39. PMID 10670014.  In animals these reactions involve complex organic molecules being 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.Nelson N, Ben-Shem A (2004). "The complex architecture of oxygenic photosynthesis". Nat Rev Mol Cell Biol 5 (12): 971-82. PMID 15573135. 

The most common set of catabolic reactions in animals can be separated into three main stages. In the first, 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 yet smaller molecules, usually acetyl coenzyme A (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

Further information: Digestion and gastrointestinal tract

Macromolecules such as starch, cellulose or proteins cannot be rapidly taken up by cells and need to 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 monosaccharides.

Microbes simply secrete digestive enzymes into their surroundings,Häse C, Finkelstein R (1993). "Bacterial extracellular zinc-containing metalloproteases". Microbiol Rev 57 (4): 823-37. PMID 8302217. Gupta R, Gupta N, Rathi P (2004). "Bacterial lipases: an overview of production, purification and biochemical properties". Appl Microbiol Biotechnol 64 (6): 763-81. PMID 14966663.  while animals only secrete these enzymes from specialized cells in their guts.Hoyle T (1997). "The digestive system: linking theory and practice". Br J Nurs 6 (22): 1285–91. PMID 9470654.  The amino acids or sugars released by these extracellular enzymes are then pumped into cells by specific active transport proteins.Souba W, Pacitti A (1992). "How amino acids get into cells: mechanisms, models, menus, and mediators". JPEN J Parenter Enteral Nutr 16 (6): 569-78. PMID 1494216. Barrett M, Walmsley A, Gould G (1999). "Structure and function of facilitative sugar transporters". Curr Opin Cell Biol 11 (4): 496–502. PMID 10449337. 

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

Energy from organic compounds

Further information: Cellular respiration, fermentation, carbohydrate catabolism, fat catabolism and protein catabolism

Carbohydrate catabolism is the breakdown of carbohydrates into smaller units. Carbohydrates are usually taken into cells once they have been digested into monosaccharides.Bell G, Burant C, Takeda J, Gould G (1993). "Structure and function of mammalian facilitative sugar transporters". J Biol Chem 268 (26): 19161-4. PMID 8366068.  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.Bouché C, Serdy S, Kahn C, Goldfine A (2004). "The cellular fate of glucose and its relevance in type 2 diabetes". Endocr Rev 25 (5): 807-30. PMID 15466941.  Pyruvate is an intermediate in several metabolic pathways, but the majority is converted to acetyl-CoA 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 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.

Amino acids are either used to synthesize proteins and other biomolecules, or oxidized to urea and carbon dioxide as a source of energy.Sakami W, Harrington H (1963). "Amino acid metabolism". Annu Rev Biochem 32: 355-98. PMID 14144484.  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.Brosnan J (2000). "Glutamate, at the interface between amino acid and carbohydrate metabolism". J Nutr 130 (4S Suppl): 988S-90S. PMID 10736367.  The glucogenic amino acids can also be converted into glucose, through gluconeogenesis (discussed below).Young V, Ajami A (2001). "Glutamine: the emperor or his clothes?". J Nutr 131 (9 Suppl): 2449S-59S; discussion 2486S-7S. PMID 11533293. 

Energy transformations

Oxidative phosphorylation

Structure of ATP synthase, the proton channel and rotating stalk are shown in blue and the synthase subunits in red.

Further information: Oxidative phosphorylation, chemiosmosis and mitochondrion

In oxidative phosphorylation, the electrons removed from food molecules in pathways such as the citric acid cycle are transferred to oxygen and the energy released 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.Hosler J, Ferguson-Miller S, Mills D (2006). "Energy transduction: proton transfer through the respiratory complexes". Annu Rev Biochem 75: 165-87. PMID 16756489.  These proteins use the energy released from passing electrons from reduced molecules like NADH onto oxygen to pump protons across a membrane.Schultz B, Chan S (2001). "Structures and proton-pumping strategies of mitochondrial respiratory enzymes". Annu Rev Biophys Biomol Struct 30: 23–65. PMID 11340051. 

Pumping protons out of the mitochondria creates a proton concentration difference across the membrane and generates an electrochemical gradient.Capaldi R, Aggeler R (2002). "Mechanism of the F(1)F(0)-type ATP synthase, a biological rotary motor". Trends Biochem Sci 27 (3): 154-60. PMID 11893513.  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.

Energy from inorganic compounds

Further information: Microbial metabolism and 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,Friedrich B, Schwartz E (1993). "Molecular biology of hydrogen utilization in aerobic chemolithotrophs". Annu Rev Microbiol 47: 351-83. PMID 8257102.  reduced sulfur compounds (such as sulfide, hydrogen sulfide and thiosulfate),Friedrich C (1998). "Physiology and genetics of sulfur-oxidizing bacteria". Adv Microb Physiol 39: 235-89. PMID 9328649.  ferrous iron (FeII)Weber K, Achenbach L, Coates J (2006). "Microorganisms pumping iron: anaerobic microbial iron oxidation and reduction". Nat Rev Microbiol 4 (10): 752-64. PMID 16980937.  or ammoniaJetten M, Strous M, van de Pas-Schoonen K, Schalk J, van Dongen U, van de Graaf A, Logemann S, Muyzer G, van Loosdrecht M, Kuenen J (1998). "The anaerobic oxidation of ammonium". FEMS Microbiol Rev 22 (5): 421-37. PMID 9990725.  as sources of reducing power and they gain energy from the oxidation of these compounds with electron acceptors such as oxygen or nitrite.Simon J (2002). "Enzymology and bioenergetics of respiratory nitrite ammonification". FEMS Microbiol Rev 26 (3): 285–309. PMID 12165429.  These microbial processes are important in global biogeochemical cycles such as acetogenesis, nitrification and denitrification and are critical for soil fertility.Conrad R (1996). "Soil microorganisms as controllers of atmospheric trace gases (H2, CO, CH4, OCS, N2O, and NO)". Microbiol Rev 60 (4): 609-40. PMID 8987358. Barea J, Pozo M, Azcón R, Azcón-Aguilar C (2005). "Microbial co-operation in the rhizosphere". J Exp Bot 56 (417): 1761–78. PMID 15911555. 

Energy from light

Further information: Phototroph, photophosphorylation, 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.van der Meer M, Schouten S, Bateson M, Nübel U, Wieland A, Kühl M, de Leeuw J, Sinninghe Damsté J, Ward D (2005). "Diel variations in carbon metabolism by green nonsulfur-like bacteria in alkaline siliceous hot spring microbial mats from Yellowstone National Park". Appl Environ Microbiol 71 (7): 3978–86. PMID 16000812. Tichi M, Tabita F (2001). "Interactive control of Rhodobacter capsulatus redox-balancing systems during phototrophic metabolism". J Bacteriol 183 (21): 6344–54. PMID 11591679. 

The capture of solar energy is a process that is similar in principle to oxidative phosphorylation, as it involves energy being stored as a proton concentration gradient and this proton motive force then driving ATP synthesis. The electrons needed to drive this electron transport chain come from light-gathering proteins called photosynthetic reaction centres. These structures are classed into two types depending on the type of photosynthetic pigment present, with most photosynthetic bacteria only having one type of reaction center, while plants and cyanobacteria have two.Allen J, Williams J (1998). "Photosynthetic reaction centers". FEBS Lett 438 (1–2): 5–9. PMID 9821949. 

In plants, 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.Nelson N, Ben-Shem A (2004). "The complex architecture of oxygenic photosynthesis". Nat Rev Mol Cell Biol 5 (12): 971-82. PMID 15573135.  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.Munekage Y, Hashimoto M, Miyake C, Tomizawa K, Endo T, Tasaka M, Shikanai T (2004). "Cyclic electron flow around photosystem I is essential for photosynthesis". Nature 429 (6991): 579-82. PMID 15175756. 

Anabolism

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. Firstly, 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 differ in how many of the molecules in their cells they can construct for themselves. 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 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 fixation

Further information: Photosynthesis, carbon fixation and chemosynthesis

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

Photosynthesis is the synthesis of carbohydrates from sunlight, carbon dioxide (CO₂) and water, with oxygen produced as a waste product. 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. This carbon-fixation reaction is carried out by the enzyme RuBisCO as part of the Calvin – Benson cycle.Miziorko H, Lorimer G (1983). "Ribulose-1,5-bisphosphate carboxylase-oxygenase". Annu Rev Biochem 52: 507-35. PMID 6351728.  Three types of photosynthesis occur in plants, C3 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.Dodd A, Borland A, Haslam R, Griffiths H, Maxwell K (2002). "Crassulacean acid metabolism: plastic, fantastic". J Exp Bot 53 (369): 569-80. PMID 11886877. 

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,Hügler M, Wirsen C, Fuchs G, Taylor C, Sievert S (2005). "Evidence for autotrophic CO2 fixation via the reductive tricarboxylic acid cycle by members of the epsilon subdivision of proteobacteria". J Bacteriol 187 (9): 3020–7. PMID 15838028.  or the carboxylation of acetyl-CoA.Strauss G, Fuchs G (1993). "Enzymes of a novel autotrophic CO2 fixation pathway in the phototrophic bacterium Chloroflexus aurantiacus, the 3-hydroxypropionate cycle". Eur J Biochem 215 (3): 633-43. PMID 8354269. Wood H (1991). "Life with CO or CO2 and H2 as a source of carbon and energy". FASEB J 5 (2): 156-63. PMID 1900793.  Prokaryotic chemoautotrophs also fix CO₂ through the Calvin – Benson cycle, but use energy from inorganic compounds to drive the reaction.Shively J, van Keulen G, Meijer W (1998). "Something from almost nothing: carbon dioxide fixation in chemoautotrophs". Annu Rev Microbiol 52: 191–230. PMID 9891798. 

Carbohydrates and glycans

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 converts pyruvate to glucose-6-phosphate through a series of intermediates, many of which are shared with glycolysis. 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.Boiteux A, Hess B (1981). "Design of glycolysis". Philos Trans R Soc Lond B Biol Sci 293 (1063): 5–22. PMID 6115423. Pilkis S, el-Maghrabi M, Claus T (1990). "Fructose-2,6-bisphosphate in control of hepatic gluconeogenesis. From metabolites to molecular genetics". Diabetes Care 13 (6): 582-99. PMID 2162755. 

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.Ensign S (2006). "Revisiting the glyoxylate cycle: alternate pathways for microbial acetate assimilation". Mol Microbiol 61 (2): 274-6. PMID 16856935.  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.Finn P, Dice J (2006). "Proteolytic and lipolytic responses to starvation". Nutrition 22 (7–8): 830-44. PMID 16815497.  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.Kornberg H, Krebs H (1957). "Synthesis of cell constituents from C2-units by a modified tricarboxylic acid cycle". Nature 179 (4568): 988-91. PMID 13430766. 

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.Rademacher T, Parekh R, Dwek R (1988). "Glycobiology". Annu Rev Biochem 57: 785–838. PMID 3052290.  The polysaccharides produced can have structural or metabolic functions themselves, or be transferred to lipids and proteins by enzymes called oligosaccharyltransferases.Opdenakker G, Rudd P, Ponting C, Dwek R (1993). "Concepts and principles of glycobiology". FASEB J 7 (14): 1330–7. PMID 8224606. McConville M, Menon A (2000). "Recent developments in the cell biology and biochemistry of glycosylphosphatidylinositol lipids (review)". Mol Membr Biol 17 (1): 1–16. PMID 10824734. 

Fatty acids, isoprenoids and steroids

Further information: Fatty acid synthesis, 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 actyl group, reduce it to an alcohol, de