Editing Metabolism (section)

==Anabolism==
{{further|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 smaller and simpler precursors. Anabolism involves three basic stages. First, the production of precursors such as [[amino acid]]s, [[monosaccharide]]s, [[Terpenoid|isoprenoids]] and [[nucleotide]]s, secondly, their activation into reactive forms using energy from ATP, and thirdly, the assembly of these precursors into complex molecules such as [[protein]]s, [[polysaccharide]]s, [[lipid]]s and [[nucleic acid]]s.<ref name="Mandal-2009">{{cite web| vauthors = Mandal A |date=2009-11-26|title=What is Anabolism?|url=https://www.news-medical.net/life-sciences/What-is-Anabolism.aspx|access-date=2020-07-04|website=News-Medical.net|language=en|archive-date=5 July 2020|archive-url=https://web.archive.org/web/20200705173136/https://www.news-medical.net/life-sciences/What-is-Anabolism.aspx|url-status=live}}</ref>

Anabolism in organisms can be different according to the source of constructed molecules in their cells. [[Autotroph]]s such as plants can construct the complex organic molecules in their cells such as polysaccharides and proteins from simple molecules like [[carbon dioxide]] and water. [[Heterotroph]]s, on the other hand, require a source of more complex substances, such as monosaccharides and amino acids, to produce these complex molecules. Organisms can be further classified by ultimate source of their energy: photoautotrophs and photoheterotrophs obtain energy from light, whereas chemoautotrophs and chemoheterotrophs obtain energy from oxidation reactions.<ref name="Mandal-2009" />

===Carbon fixation===
{{further|Photosynthesis|Carbon fixation|Chemosynthesis}}
[[File:Plagiomnium affine laminazellen.jpeg|thumb|Plant cells (bounded by purple walls) filled with chloroplasts (green), which are the site of photosynthesis]]

Photosynthesis is the synthesis of carbohydrates from sunlight and [[carbon dioxide]] (CO<sub>2</sub>). In plants, cyanobacteria and algae, oxygenic photosynthesis splits water, with oxygen produced as a waste product. This process uses the ATP and NADPH produced by the [[photosynthetic reaction centre]]s, as described above, to convert CO<sub>2</sub> 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 cycle|Calvin–Benson cycle]].<ref>{{cite journal | vauthors = Miziorko HM, Lorimer GH | title = Ribulose-1,5-bisphosphate carboxylase-oxygenase | journal = [[Annual Review of Biochemistry]] | volume = 52 | pages = 507–35 | year = 1983 | pmid = 6351728 | doi = 10.1146/annurev.bi.52.070183.002451 }}</ref> Three types of photosynthesis occur in plants, [[C3 carbon fixation]], [[C4 carbon fixation]] and [[Crassulacean acid metabolism|CAM photosynthesis]]. These differ by the route that carbon dioxide takes to the Calvin cycle, with C3 plants fixing CO<sub>2</sub> directly, while C4 and CAM photosynthesis incorporate the CO<sub>2</sub> into other compounds first, as adaptations to deal with intense sunlight and dry conditions.<ref>{{cite journal | vauthors = Dodd AN, Borland AM, Haslam RP, Griffiths H, Maxwell K | title = Crassulacean acid metabolism: plastic, fantastic | journal = Journal of Experimental Botany | volume = 53 | issue = 369 | pages = 569–80 | date = April 2002 | pmid = 11886877 | doi = 10.1093/jexbot/53.369.569 | doi-access = free }}</ref>

In photosynthetic [[prokaryote]]s the mechanisms of carbon fixation are more diverse. Here, carbon dioxide can be fixed by the Calvin–Benson cycle, a [[Reverse Krebs cycle|reversed citric acid]] cycle,<ref>{{cite journal | vauthors = Hügler M, Wirsen CO, Fuchs G, Taylor CD, Sievert SM | title = Evidence for autotrophic CO2 fixation via the reductive tricarboxylic acid cycle by members of the epsilon subdivision of proteobacteria | journal = Journal of Bacteriology | volume = 187 | issue = 9 | pages = 3020–7 | date = May 2005 | pmid = 15838028 | pmc = 1082812 | doi = 10.1128/JB.187.9.3020-3027.2005 }}</ref> or the [[carboxylation]] of acetyl-CoA.<ref>{{cite journal | vauthors = Strauss G, Fuchs G | title = Enzymes of a novel autotrophic CO2 fixation pathway in the phototrophic bacterium Chloroflexus aurantiacus, the 3-hydroxypropionate cycle | journal = European Journal of Biochemistry | volume = 215 | issue = 3 | pages = 633–43 | date = August 1993 | pmid = 8354269 | doi = 10.1111/j.1432-1033.1993.tb18074.x | doi-access = free }}</ref><ref>{{cite journal | vauthors = Wood HG | title = Life with CO or CO2 and H2 as a source of carbon and energy | journal = FASEB Journal | volume = 5 | issue = 2 | pages = 156–63 | date = February 1991 | pmid = 1900793 | doi = 10.1096/fasebj.5.2.1900793 | doi-access = free | s2cid = 45967404 }}</ref> Prokaryotic [[Chemotroph|chemoautotrophs]] also fix CO<sub>2</sub> through the Calvin–Benson cycle, but use energy from inorganic compounds to drive the reaction.<ref>{{cite journal | vauthors = Shively JM, van Keulen G, Meijer WG | title = Something from almost nothing: carbon dioxide fixation in chemoautotrophs | journal = [[Annual Review of Microbiology]] | volume = 52 | pages = 191–230 | year = 1998 | pmid = 9891798 | doi = 10.1146/annurev.micro.52.1.191 }}</ref>

===Carbohydrates and glycans===
{{further|Gluconeogenesis|Glyoxylate cycle|Glycogenesis|Glycosylation}}

In carbohydrate anabolism, simple organic acids can be converted into [[monosaccharide]]s such as [[glucose]] and then used to assemble [[polysaccharide]]s such as [[starch]]. The generation of [[glucose]] from compounds like [[pyruvate]], [[lactic acid|lactate]], [[glycerol]], [[glycerate 3-phosphate]] and [[amino acid]]s is called [[gluconeogenesis]]. Gluconeogenesis converts pyruvate to [[glucose-6-phosphate]] through a series of intermediates, many of which are shared with [[glycolysis]].<ref name="Bouché-2004"/> 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]].<ref>{{cite journal | vauthors = Boiteux A, Hess B | title = Design of glycolysis | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 293 | issue = 1063 | pages = 5–22 | date = June 1981 | pmid = 6115423 | doi = 10.1098/rstb.1981.0056 | doi-access = free | bibcode = 1981RSPTB.293....5B }}</ref><ref>{{cite journal | vauthors = Pilkis SJ, el-Maghrabi MR, Claus TH | title = Fructose-2,6-bisphosphate in control of hepatic gluconeogenesis. From metabolites to molecular genetics | journal = Diabetes Care | volume = 13 | issue = 6 | pages = 582–99 | date = June 1990 | pmid = 2162755 | doi = 10.2337/diacare.13.6.582 | s2cid = 44741368 }}</ref>

Although fat is a common way of storing energy, in [[vertebrate]]s such as humans the [[fatty acid]]s 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.<ref name="Ensign-2006">{{cite journal | vauthors = Ensign SA | title = Revisiting the glyoxylate cycle: alternate pathways for microbial acetate assimilation | journal = Molecular Microbiology | volume = 61 | issue = 2 | pages = 274–6 | date = July 2006 | pmid = 16856935 | doi = 10.1111/j.1365-2958.2006.05247.x | s2cid = 39986630 | doi-access = free }}</ref> As a result, after long-term starvation, vertebrates need to produce [[Ketone body|ketone bodies]] from fatty acids to replace glucose in tissues such as the brain that cannot metabolize fatty acids.<ref>{{cite journal | vauthors = Finn PF, Dice JF | title = Proteolytic and lipolytic responses to starvation | journal = Nutrition | volume = 22 | issue = 7–8 | pages = 830–44 | year = 2006 | pmid = 16815497 | doi = 10.1016/j.nut.2006.04.008 }}</ref> 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.<ref name="Ensign-2006"/><ref name="Kornberg-1957">{{cite journal | vauthors = Kornberg HL, Krebs HA | title = Synthesis of cell constituents from C2-units by a modified tricarboxylic acid cycle | journal = Nature | volume = 179 | issue = 4568 | pages = 988–91 | date = May 1957 | pmid = 13430766 | doi = 10.1038/179988a0 | s2cid = 40858130 | bibcode = 1957Natur.179..988K }}</ref> 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.<ref>{{cite journal| vauthors = Evans RD, Heather LC |date=June 2016|title=Metabolic pathways and abnormalities|journal=Surgery (Oxford)|volume=34|issue=6|pages=266–272|doi=10.1016/j.mpsur.2016.03.010|s2cid=87884121 |issn=0263-9319|url=https://ora.ox.ac.uk/objects/uuid:84c0a8e7-38e9-4de2-ba19-9f129a07987a|access-date=28 August 2020|archive-date=31 October 2020|archive-url=https://web.archive.org/web/20201031143458/https://ora.ox.ac.uk/objects/uuid:84c0a8e7-38e9-4de2-ba19-9f129a07987a|url-status=live}}</ref>

Polysaccharides and [[glycan]]s are made by the sequential addition of monosaccharides by [[glycosyltransferase]] from a reactive sugar-phosphate donor such as [[uridine diphosphate glucose]] (UDP-Glc) to an acceptor [[hydroxyl]] group on the growing polysaccharide. As any of the [[hydroxyl]] groups on the ring of the substrate can be acceptors, the polysaccharides produced can have straight or branched structures.<ref>{{cite book | vauthors = Freeze HH, Hart GW, Schnaar RL | chapter=Glycosylation Precursors |date=2015 |url=http://www.ncbi.nlm.nih.gov/books/NBK453043/ |title=Essentials of Glycobiology| veditors = Varki A, Cummings RD, Esko JD, Stanley P |edition=3rd |place=Cold Spring Harbor (NY) |publisher=Cold Spring Harbor Laboratory Press |pmid=28876856 |access-date=2020-07-08 |doi=10.1101/glycobiology.3e.005|doi-broken-date=1 November 2024 |archive-date=24 February 2022|archive-url=https://web.archive.org/web/20220224114901/https://www.ncbi.nlm.nih.gov/books/NBK453043/|url-status=live}}</ref> The polysaccharides produced can have structural or metabolic functions themselves, or be transferred to lipids and proteins by the enzymes [[oligosaccharyltransferase]]s.<ref>{{cite journal | vauthors = Opdenakker G, Rudd PM, Ponting CP, Dwek RA | title = Concepts and principles of glycobiology | journal = FASEB Journal | volume = 7 | issue = 14 | pages = 1330–7 | date = November 1993 | pmid = 8224606 | doi = 10.1096/fasebj.7.14.8224606 | doi-access = free | s2cid = 10388991 }}</ref><ref>{{cite journal | vauthors = McConville MJ, Menon AK | title = Recent developments in the cell biology and biochemistry of glycosylphosphatidylinositol lipids (review) | journal = Molecular Membrane Biology | volume = 17 | issue = 1 | pages = 1–16 | year = 2000 | pmid = 10824734 | doi = 10.1080/096876800294443 | doi-access = free }}</ref>

===Fatty acids, isoprenoids and sterol===
{{further|Fatty acid synthesis|Steroid metabolism}}
[[File:Sterol synthesis.svg|thumb|right|upright=1.6|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 synthase]]s 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, [[dehydration reaction|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,<ref>{{cite journal | vauthors = Chirala SS, Wakil SJ | title = Structure and function of animal fatty acid synthase | journal = Lipids | volume = 39 | issue = 11 | pages = 1045–53 | date = November 2004 | pmid = 15726818 | doi = 10.1007/s11745-004-1329-9 | s2cid = 4043407 }}</ref> while in plant [[plastid]]s and bacteria separate type II enzymes perform each step in the pathway.<ref>{{cite journal | vauthors = White SW, Zheng J, Zhang YM | title = The structural biology of type II fatty acid biosynthesis | journal = [[Annual Review of Biochemistry]] | volume = 74 | pages = 791–831 | year = 2005 | pmid = 15952903 | doi = 10.1146/annurev.biochem.74.082803.133524 }}</ref><ref>{{cite journal | vauthors = Ohlrogge JB, Jaworski JG | title = Regulation of Fatty Acid Synthesis | journal = [[Annual Review of Plant Physiology and Plant Molecular Biology]] | volume = 48 | pages = 109–136 | date = June 1997 | pmid = 15012259 | doi = 10.1146/annurev.arplant.48.1.109 | s2cid = 46348092 }}</ref>

[[Terpene]]s and [[terpenoid|isoprenoids]] are a large class of lipids that include the [[carotenoid]]s and form the largest class of plant [[natural product]]s.<ref>{{cite journal | vauthors = Dubey VS, Bhalla R, Luthra R | title = An overview of the non-mevalonate pathway for terpenoid biosynthesis in plants | journal = Journal of Biosciences | volume = 28 | issue = 5 | pages = 637–46 | date = September 2003 | pmid = 14517367 | doi = 10.1007/BF02703339 | url = http://www.ias.ac.in/jbiosci/sep2003/637.pdf | url-status = dead | s2cid = 27523830 | archive-url = https://web.archive.org/web/20070415213325/http://www.ias.ac.in/jbiosci/sep2003/637.pdf | archive-date = 15 April 2007 }}</ref> These compounds are made by the assembly and modification of [[isoprene]] units donated from the reactive precursors [[isopentenyl pyrophosphate]] and [[dimethylallyl pyrophosphate]].<ref name="Kuzuyama-2003">{{cite journal | vauthors = Kuzuyama T, Seto H | title = Diversity of the biosynthesis of the isoprene units | journal = Natural Product Reports | volume = 20 | issue = 2 | pages = 171–83 | date = April 2003 | pmid = 12735695 | doi = 10.1039/b109860h }}</ref> These precursors can be made in different ways. In animals and archaea, the [[mevalonate pathway]] produces these compounds from acetyl-CoA,<ref>{{cite journal | vauthors = Grochowski LL, Xu H, White RH | title = Methanocaldococcus jannaschii uses a modified mevalonate pathway for biosynthesis of isopentenyl diphosphate | journal = Journal of Bacteriology | volume = 188 | issue = 9 | pages = 3192–8 | date = May 2006 | pmid = 16621811 | pmc = 1447442 | doi = 10.1128/JB.188.9.3192-3198.2006 }}</ref> while in plants and bacteria the [[non-mevalonate pathway]] uses pyruvate and [[glyceraldehyde 3-phosphate]] as substrates.<ref name="Kuzuyama-2003"/><ref>{{cite journal | vauthors = Lichtenthaler HK | title = The 1-Deoxy-D-Xylulose-5-Phosphate Pathway of Isoprenoid Biosynthesis in Plants | journal = [[Annual Review of Plant Physiology and Plant Molecular Biology]] | volume = 50 | pages = 47–65 | date = June 1999 | pmid = 15012203 | doi = 10.1146/annurev.arplant.50.1.47 }}</ref> One important reaction that uses these activated isoprene donors is [[steroid biosynthesis|sterol biosynthesis]]. Here, the isoprene units are joined to make [[squalene]] and then folded up and formed into a set of rings to make [[lanosterol]].<ref name="Schroepfer-1981">{{cite journal | vauthors = Schroepfer GJ | title = Sterol biosynthesis | journal = [[Annual Review of Biochemistry]] | volume = 50 | pages = 585–621 | year = 1981 | pmid = 7023367 | doi = 10.1146/annurev.bi.50.070181.003101 }}</ref> Lanosterol can then be converted into other sterols such as [[cholesterol]] and [[ergosterol]].<ref name="Schroepfer-1981"/><ref>{{cite journal | vauthors = Lees ND, Skaggs B, Kirsch DR, Bard M | title = Cloning of the late genes in the ergosterol biosynthetic pathway of Saccharomyces cerevisiae--a review | journal = Lipids | volume = 30 | issue = 3 | pages = 221–6 | date = March 1995 | pmid = 7791529 | doi = 10.1007/BF02537824 | s2cid = 4019443 }}</ref>

===Proteins===
{{further|Protein biosynthesis|Amino acid synthesis}}

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 acid]]s must be obtained from food.<ref name="Nelson-2005"/> Some simple [[parasite]]s, such as the bacteria ''[[Mycoplasma pneumoniae]]'', lack all amino acid synthesis and take their amino acids directly from their hosts.<ref>{{cite journal | vauthors = Himmelreich R, Hilbert H, Plagens H, Pirkl E, Li BC, Herrmann R | title = Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae | journal = Nucleic Acids Research | volume = 24 | issue = 22 | pages = 4420–49 | date = November 1996 | pmid = 8948633 | pmc = 146264 | doi = 10.1093/nar/24.22.4420 }}</ref> All amino acids are synthesized from intermediates in glycolysis, the citric acid cycle, or the pentose phosphate pathway. Nitrogen is provided by [[glutamate]] and [[glutamine]]. Nonessensial amino acid synthesis depends on the formation of the appropriate alpha-keto acid, which is then [[Transaminase|transaminated]] to form an amino acid.<ref>{{cite book | vauthors = Guyton AC, Hall JE |title=Textbook of Medical Physiology |url=https://archive.org/details/textbookmedicalp00acgu |url-access=limited |publisher=Elsevier |year=2006 |location=Philadelphia |pages=[https://archive.org/details/textbookmedicalp00acgu/page/n889 855]–6 |isbn=978-0-7216-0240-0}}</ref>

Amino acids are made into proteins by being joined in a chain of [[peptide bond]]s. Each different protein has a unique sequence of amino acid residues: this is its [[primary structure]]. Just as the letters of the alphabet can be combined to form an almost endless variety of words, amino acids can be linked in varying sequences to form a huge variety of proteins. Proteins are made from amino acids that have been activated by attachment to a [[transfer RNA]] molecule through an [[ester]] bond. This [[aminoacyl-tRNA]] precursor is produced in an [[Adenosine triphosphate|ATP]]-dependent reaction carried out by an [[aminoacyl tRNA synthetase]].<ref>{{cite journal | vauthors = Ibba M, Söll D | title = The renaissance of aminoacyl-tRNA synthesis | journal = EMBO Reports | volume = 2 | issue = 5 | pages = 382–7 | date = May 2001 | pmid = 11375928 | pmc = 1083889 | doi = 10.1093/embo-reports/kve095 | url = http://www.molcells.org/home/journal/include/downloadPdf.asp?articleuid={A158E3B4-2423-4806-9A30-4B93CDA76DA0} | url-status = dead | archive-url = https://web.archive.org/web/20110501181419/http://www.molcells.org/home/journal/include/downloadPdf.asp?articleuid=%7BA158E3B4-2423-4806-9A30-4B93CDA76DA0%7D | archive-date = 1 May 2011 }}</ref> 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]].<ref>{{cite journal | vauthors = Lengyel P, Söll D | title = Mechanism of protein biosynthesis | journal = Bacteriological Reviews | volume = 33 | issue = 2 | pages = 264–301 | date = June 1969 | pmid = 4896351 | pmc = 378322 | doi = 10.1128/MMBR.33.2.264-301.1969 }}</ref>

===Nucleotide synthesis and salvage===
{{further|Nucleotide salvage|Pyrimidine biosynthesis|Purine#Metabolism}}
Nucleotides are made from amino acids, carbon dioxide and [[formic acid]] in pathways that require large amounts of metabolic energy.<ref name="Rudolph-1994">{{cite journal | vauthors = Rudolph FB | title = The biochemistry and physiology of nucleotides | journal = The Journal of Nutrition | volume = 124 | issue = 1 Suppl | pages = 124S–127S | date = January 1994 | pmid = 8283301 | doi = 10.1093/jn/124.suppl_1.124S | doi-access = free }} {{cite journal | vauthors = Zrenner R, Stitt M, Sonnewald U, Boldt R | title = Pyrimidine and purine biosynthesis and degradation in plants | journal = [[Annual Review of Plant Biology]] | volume = 57 | pages = 805–36 | year = 2006 | issue = 1 | pmid = 16669783 | doi = 10.1146/annurev.arplant.57.032905.105421 | bibcode = 2006AnRPB..57..805Z }}</ref> Consequently, most organisms have efficient systems to salvage preformed nucleotides.<ref name="Rudolph-1994"/><ref>{{cite journal | vauthors = Stasolla C, Katahira R, Thorpe TA, Ashihara H | title = Purine and pyrimidine nucleotide metabolism in higher plants | journal = Journal of Plant Physiology | volume = 160 | issue = 11 | pages = 1271–95 | date = November 2003 | pmid = 14658380 | doi = 10.1078/0176-1617-01169 | bibcode = 2003JPPhy.160.1271S }}</ref> [[Purine]]s are synthesized as [[nucleoside]]s (bases attached to [[ribose]]).<ref name="Davies-2012">{{cite journal | vauthors = Davies O, Mendes P, Smallbone K, Malys N | title = Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism | journal = BMB Reports | volume = 45 | issue = 4 | pages = 259–64 | date = April 2012 | pmid = 22531138 | doi = 10.5483/BMBRep.2012.45.4.259 | url = http://wrap.warwick.ac.uk/49510/1/WRAP_Malys_%5B45-4%5D1204261917_%28259-264%29BMB_11-169.pdf | doi-access = free | access-date = 18 September 2019 | archive-date = 24 October 2020 | archive-url = https://web.archive.org/web/20201024132423/http://wrap.warwick.ac.uk/49510/1/WRAP_Malys_%5B45-4%5D1204261917_%28259-264%29BMB_11-169.pdf | url-status = live }}</ref> 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]] [[folic acid|tetrahydrofolate]]. [[Pyrimidine]]s, on the other hand, are synthesized from the base [[Pyrimidinecarboxylic acid|orotate]], which is formed from glutamine and aspartate.<ref>{{cite journal | vauthors = Smith JL | title = Enzymes of nucleotide synthesis | journal = Current Opinion in Structural Biology | volume = 5 | issue = 6 | pages = 752–7 | date = December 1995 | pmid = 8749362 | doi = 10.1016/0959-440X(95)80007-7 }}</ref>