Editing Vitamin C (section)

==Synthesis==
Most animals and plants are able to synthesize vitamin C through a sequence of [[enzyme]]-driven steps, which convert [[monosaccharides]] to vitamin C. Yeasts do not make {{sm|l}}-ascorbic acid but rather its [[stereoisomer]], [[erythorbic acid]].<ref name="pmid17971855">{{cite journal | vauthors = Branduardi P, Fossati T, Sauer M, Pagani R, Mattanovich D, Porro D | title = Biosynthesis of vitamin C by yeast leads to increased stress resistance | journal = PLOS ONE | volume = 2 | issue = 10 | pages = e1092 | date = October 2007 | pmid = 17971855 | pmc = 2034532 | doi = 10.1371/journal.pone.0001092 | bibcode = 2007PLoSO...2.1092B | doi-access = free | title-link = doi }}</ref> In plants, synthesis is accomplished through the conversion of [[mannose]] or [[galactose]] to ascorbic acid.<ref name="pmid9620799">{{cite journal | vauthors = Wheeler GL, Jones MA, Smirnoff N | title = The biosynthetic pathway of vitamin C in higher plants | journal = Nature | volume = 393 | issue = 6683 | pages = 365–9 | date = May 1998 | pmid = 9620799 | doi = 10.1038/30728 | bibcode = 1998Natur.393..365W | s2cid = 4421568 }}</ref><ref name="Stone">{{cite journal | url = http://orthomolecular.org/library/jom/1972/pdf/1972-v01n02%2603-p082.pdf | title = The natural history of ascorbic acid in the evolution of the mammals and primates and is significance for present-day man evolution of mammals and primates | vauthors = Stone I | year = 1972 | journal = Journal of Orthomolecular Psychiatry | volume = 1 | issue = 2 | pages = 82–9 | access-date = December 31, 2023 | archive-date = October 2, 2023 | archive-url = https://web.archive.org/web/20231002185424/http://orthomolecular.org/library/jom/1972/pdf/1972-v01n02%2603-p082.pdf | url-status = live }}</ref> In animals, the starting material is [[glucose]]. In some species that synthesize ascorbate in the liver (including [[mammal]]s and [[Passerine|perching bird]]s), the glucose is extracted from [[glycogen]]; ascorbate synthesis is a glycogenolysis-dependent process.<ref name="pmid11458272">{{cite journal | vauthors = Bánhegyi G, Mándl J | title = The hepatic glycogenoreticular system | journal = Pathology & Oncology Research | volume = 7 | issue = 2 | pages = 107–10 | year = 2001 | pmid = 11458272 | doi = 10.1007/BF03032575 | citeseerx = 10.1.1.602.5659 | s2cid = 20139913 }}</ref> In humans and in animals that cannot synthesize vitamin C, the enzyme [[gulonolactone oxidase|{{sm|l}}-gulonolactone oxidase]] (GULO), which catalyzes the last step in the biosynthesis, is highly mutated and non-functional.<ref name="valpuesta">{{cite journal | title = Biosynthesis of L-ascorbic acid in plants: new pathways for an old antioxidant | vauthors = Valpuesta V, Botella MA | journal = Trends in Plant Science | year = 2004 | volume = 9 | issue = 12 | pages = 573–7 | pmid = 15564123 | doi = 10.1016/j.tplants.2004.10.002 | bibcode = 2004TPS.....9..573V | url = http://www.bmbq.uma.es/lbbv/index_archivos/pdf/Valpuesta%202004.pdf | access-date = October 8, 2018 | archive-date = December 25, 2020 | archive-url = https://web.archive.org/web/20201225062850/http://www.bmbq.uma.es/lbbv/index_archivos/pdf/Valpuesta%202004.pdf | url-status = live }}</ref><ref name="pmid1962571">{{cite journal | vauthors = Nishikimi M, Yagi K | title = Molecular basis for the deficiency in humans of gulonolactone oxidase, a key enzyme for ascorbic acid biosynthesis | journal = Am J Clin Nutr | volume = 54 | issue = 6 Suppl | pages = 1203S–8S | date = December 1991 | pmid = 1962571 | doi = 10.1093/ajcn/54.6.1203s| doi-access = free | title-link = doi }}</ref><ref name="pmid1400507">{{cite journal | vauthors = Nishikimi M, Kawai T, Yagi K | title = Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species | journal = The Journal of Biological Chemistry | volume = 267 | issue = 30 | pages = 21967–72 | date = October 1992 | doi = 10.1016/S0021-9258(19)36707-9 | pmid = 1400507 | doi-access = free | title-link = doi }}</ref><ref name="pmid10572964">{{cite journal | vauthors = Ohta Y, Nishikimi M | title = Random nucleotide substitutions in primate nonfunctional gene for L-gulono-gamma-lactone oxidase, the missing enzyme in L-ascorbic acid biosynthesis | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1472 | issue = 1–2 | pages = 408–11 | date = October 1999 | pmid = 10572964 | doi = 10.1016/S0304-4165(99)00123-3 }}</ref>

=== Animal synthesis ===
There is some information on serum vitamin C concentrations maintained in animal species that are able to synthesize vitamin C. One study of several breeds of dogs reported an average of 35.9&nbsp;μmol/L.<ref name="pmid11666145">{{cite journal |vauthors=Wang S, Berge GE, Sund RB |title=Plasma ascorbic acid concentrations in healthy dogs |journal=Res. Vet. Sci. |volume=71 |issue=1 |pages=33–5 |date=August 2001 |pmid=11666145 |doi=10.1053/rvsc.2001.0481 }}</ref> A report on goats, sheep and cattle reported ranges of 100–110, 265–270 and 160–350&nbsp;μmol/L, respectively.<ref name=Ranjan2012>{{cite journal |vauthors=Ranjan R, Ranjan A, Dhaliwal GS, Patra RC |s2cid=1674389 |title=l-Ascorbic acid (vitamin C) supplementation to optimize health and reproduction in cattle |journal=Vet Q |volume=32 |issue=3–4 |pages=145–50 |date=2012 |pmid=23078207 |doi=10.1080/01652176.2012.734640 }}</ref>

The biosynthesis of ascorbic acid in [[vertebrates]] starts with the formation of UDP-glucuronic acid. UDP-glucuronic acid is formed when UDP-glucose undergoes two oxidations catalyzed by the enzyme UDP-glucose 6-dehydrogenase. UDP-glucose 6-dehydrogenase uses the co-factor NAD<sup>+</sup> as the electron acceptor. The transferase UDP-glucuronate pyrophosphorylase removes a [[Uridine monophosphate|UMP]] and [[glucuronokinase]], with the cofactor ADP, removes the final phosphate leading to [[glucuronic acid|{{sm|d}}-glucuronic acid]]. The aldehyde group of this compound is reduced to a primary alcohol using the enzyme [[glucuronate reductase]] and the cofactor NADPH, yielding {{sm|l}}-gulonic acid. This is followed by lactone formation{{Em dash}}utilizing the hydrolase [[gluconolactonase]]{{Em dash}}between the carbonyl on C1 and hydroxyl group on C4. {{sm|l}}-Gulonolactone then reacts with oxygen, catalyzed by the enzyme [[L-gulonolactone oxidase]] (which is nonfunctional in humans and other [[Haplorrhini]] primates; see [[Pseudogene#Unitary pseudogenes|Unitary pseudogenes]]) and the cofactor FAD+. This reaction produces 2-oxogulonolactone (2-keto-gulonolactone), which spontaneously undergoes [[enolization]] to form ascorbic acid.<ref name="Stone" /><ref name="West Sussex 2009">{{cite book | vauthors = Dewick PM | title = Medicinal natural products: a biosynthetic approach | edition = 3rd | year = 2009 | isbn = 978-0-470-74167-2 | publisher = John Wiley and Sons | page = 493}}</ref><ref name=Linster2007>{{cite journal | vauthors = Linster CL, Van Schaftingen E | title = Vitamin C. Biosynthesis, recycling and degradation in mammals | journal = The FEBS Journal | volume = 274 | issue = 1 | pages = 1–22 | date = January 2007 | pmid = 17222174 | doi = 10.1111/j.1742-4658.2006.05607.x | s2cid = 21345196 | doi-access = free | title-link = doi }}</ref> Reptiles and older orders of birds make ascorbic acid in their kidneys. Recent orders of birds and most mammals make ascorbic acid in their liver.<ref name="Stone" />

====Non-synthesizers====
Some mammals have lost the ability to synthesize vitamin C, including [[simian]]s and [[tarsier]]s, which together make up one of two major [[primate]] suborders, [[Haplorhini]]. This group includes humans. The other more primitive primates ([[Strepsirrhini]]) have the ability to make vitamin C. Synthesis does not occur in some species in the rodent family [[Caviidae]], which includes [[guinea pig]]s and [[capybara]]s, but does occur in other rodents, including [[rat]]s and [[mouse|mice]].<ref name="Miller-2014">{{cite book | vauthors = Miller RE, Fowler ME | title = Fowler's zoo and wild animal medicine, volume 8 | page = 389 | url = https://books.google.com/books?id=llBcBAAAQBAJ&q=Caviidae+%22vitamin+C%22&pg=PA389 |access-date=2 June 2016 |url-status=live |archive-url=https://web.archive.org/web/20161207032904/https://books.google.com/books?id=llBcBAAAQBAJ&pg=PA389&lpg=PA389&dq=Caviidae+%22vitamin+C%22&source=bl&ots=ofF-Bu-mx-&sig=nPEZZ68O7v26lmGS9eAGfmaUZ1o&hl=en&sa=X&ved=0ahUKEwiIk471gInNAhUT0WMKHWlpAqAQ6AEISDAH#v=onepage&q=Caviidae%20%22vitamin%20C%22&f=false |archive-date=December 7, 2016 | isbn = 978-1-4557-7399-2 |date=2014 | publisher = Elsevier Health Sciences }}</ref>

Synthesis does not occur in most bat species,<ref name="Jenness-1980">{{cite journal |doi=10.1016/0305-0491(80)90131-5 |title=Variation of l-gulonolactone oxidase activity in placental mammals |year=1980 |vauthors=Jenness R, Birney E, Ayaz K |journal=Comparative Biochemistry and Physiology B |volume=67 |issue=2 |pages=195–204 }}</ref> but there are at least two species, frugivorous bat ''[[Rousettus leschenaultii]]'' and insectivorous bat ''[[Hipposideros armiger]]'', that retain (or regained) their ability of vitamin C production.<ref name="pmid21037206">{{cite journal | vauthors = Cui J, Pan YH, Zhang Y, Jones G, Zhang S | title = Progressive pseudogenization: vitamin C synthesis and its loss in bats | journal = Molecular Biology and Evolution | volume = 28 | issue = 2 | pages = 1025–31 | date = February 2011 | pmid = 21037206 | doi = 10.1093/molbev/msq286 | doi-access = free | title-link = doi }}</ref><ref name="pmid22069493">{{cite journal | vauthors = Cui J, Yuan X, Wang L, Jones G, Zhang S | title = Recent loss of vitamin C biosynthesis ability in bats | journal = PLOS ONE | volume = 6 | issue = 11 | pages = e27114 | date = Nov 2011 | pmid = 22069493 | pmc = 3206078 | doi = 10.1371/journal.pone.0027114 | doi-access = free | title-link = doi | bibcode = 2011PLoSO...627114C }}</ref> A number of species of passerine birds also do not synthesize, but not all of them, and those that do not are not clearly related; it has been proposed that the ability was lost separately a number of times in birds.<ref name="Martinez del Rio_1997">{{cite journal |title=Can passerines synthesize vitamin C? | vauthors = Martinez del Rio C |journal= The Auk |date=July 1997 |volume=114 |issue=3 |pages=513–6 |jstor=4089257 |doi=10.2307/4089257 | doi-access = free | title-link = doi }}</ref> In particular, the ability to synthesize vitamin C is presumed to have been lost and then later re-acquired in at least two cases.<ref name="pmid22294879">{{cite journal | vauthors = Drouin G, Godin JR, Pagé B | title = The genetics of vitamin C loss in vertebrates | journal = Current Genomics | volume = 12 | issue = 5 | pages = 371–8 | date = August 2011 | pmid = 22294879 | pmc = 3145266 | doi = 10.2174/138920211796429736 }}</ref> The ability to synthesize vitamin{{nbsp}}C has also been lost in about 96% of [[Extant taxon|extant]] fish<ref name=Berra>{{cite book | vauthors = Berra TM |title=Freshwater fish distribution |url=https://books.google.com/books?id=K-1Ygw6XwFQC&pg=PA55 |year=2008 |publisher=[[University of Chicago Press]] |isbn=978-0-226-04443-9|page=55}}</ref> (the [[teleosts]]).<ref name="pmid22294879" />

On a milligram consumed per kilogram of body weight basis, simian non-synthesizer species consume the vitamin in amounts 10 to 20 times higher than what is recommended by governments for humans.<ref name="pmid10378206">{{cite journal | vauthors = Milton K | title = Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us? | journal = Nutrition | volume = 15 | issue = 6 | pages = 488–98 | date = June 1999 | pmid = 10378206 | doi = 10.1016/S0899-9007(99)00078-7 | url = http://www.direct-ms.org/pdf/EvolutionPaleolithic/primaten.pdf | archive-url = https://web.archive.org/web/20170810090049/http://www.direct-ms.org/pdf/EvolutionPaleolithic/primaten.pdf | df = mdy-all | url-status = live | archive-date = 10 August 2017 | citeseerx = 10.1.1.564.1533}}</ref> This discrepancy constituted some of the basis of the controversy on human recommended dietary allowances being set too low.<ref name=pmid5275366 /> However, simian consumption does not indicate simian requirements. Merck's veterinary manual states that daily intake of vitamin C at 3–6&nbsp;mg/kg prevents scurvy in non-human primates.<ref name="Parrott-2022">{{cite web |url=https://www.msdvetmanual.com/exotic-and-laboratory-animals/nonhuman-primates/nutritional-diseases-of-nonhuman-primates |title=Nutritional diseases of nonhuman primates | vauthors = Parrott T |date=October 2022 |website=Merck Veterinary Manual |access-date=24 December 2023 |archive-date=December 24, 2023 |archive-url=https://web.archive.org/web/20231224173242/https://www.msdvetmanual.com/exotic-and-laboratory-animals/nonhuman-primates/nutritional-diseases-of-nonhuman-primates |url-status=live }}</ref> By way of comparison, across several countries, the recommended dietary intake for adult humans is in the range of 1–2&nbsp;mg/kg.

====Evolution of animal synthesis====
Ascorbic acid is a common enzymatic [[cofactor (biochemistry)|cofactor]] in mammals used in the synthesis of [[collagen]], as well as a powerful [[reducing agent]] capable of rapidly scavenging a number of [[reactive oxygen species]] (ROS). Given that ascorbate has these important functions, it is surprising that the ability to synthesize this molecule has not always been conserved. In fact, anthropoid primates, ''[[Guinea pig|Cavia porcellus]]'' (guinea pigs), [[teleost]] fishes, most bats, and some [[passerine]] birds have all independently lost the ability to internally synthesize vitamin C in either the kidney or the liver.<ref name="pmid21140195">{{cite journal | vauthors = Lachapelle MY, Drouin G | title = Inactivation dates of the human and guinea pig vitamin C genes | journal = Genetica | volume = 139 | issue = 2 | pages = 199–207 | date = February 2011 | pmid = 21140195 | doi = 10.1007/s10709-010-9537-x | s2cid = 7747147 }}</ref><ref name="pmid22294879"/> In all of the cases where genomic analysis was done on an ascorbic acid [[Auxotrophy|auxotroph]], the origin of the change was found to be a result of loss-of-function mutations in the gene that encodes <small>L</small>-gulono-γ-lactone oxidase, the enzyme that catalyzes the last step of the ascorbic acid pathway outlined above.<ref name="pmid23404229">{{cite journal | vauthors = Yang H | s2cid = 14393449 | title = Conserved or lost: molecular evolution of the key gene GULO in vertebrate vitamin C biosynthesis | journal = Biochemical Genetics | volume = 51 | issue = 5–6 | pages = 413–25 | date = June 2013 | pmid = 23404229 | doi = 10.1007/s10528-013-9574-0 }}</ref> One explanation for the repeated loss of the ability to synthesize vitamin C is that it was the result of [[genetic drift]]; assuming that the diet was rich in vitamin{{nbsp}}C, natural selection would not act to preserve it.<ref name="pmid20210993">{{cite journal | vauthors = Zhang ZD, Frankish A, Hunt T, Harrow J, Gerstein M | title = Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates | journal = Genome Biology | volume = 11 | issue = 3 | pages = R26 | date = 2010 | pmid = 20210993 | pmc = 2864566 | doi = 10.1186/gb-2010-11-3-r26 | doi-access = free | title-link = doi }}</ref><ref name="pmid3338984">{{cite journal | vauthors = Koshizaka T, Nishikimi M, Ozawa T, Yagi K | title = Isolation and sequence analysis of a complementary DNA encoding rat liver L-gulono-gamma-lactone oxidase, a key enzyme for L-ascorbic acid biosynthesis | journal = The Journal of Biological Chemistry | volume = 263 | issue = 4 | pages = 1619–21 | date = February 1988 | doi = 10.1016/S0021-9258(19)77923-X | pmid = 3338984 | doi-access = free | title-link = doi }}</ref>

In the case of the simians, it is thought that the loss of the ability to make vitamin C may have occurred much farther back in evolutionary history than the emergence of humans or even apes, since it evidently occurred soon after the appearance of the first primates, yet sometime after the split of early primates into the two major suborders [[Haplorrhini]] (which cannot make vitamin C) and its sister suborder of non-tarsier prosimians, the [[Strepsirrhini]] ("wet-nosed" primates), which retained the ability to make vitamin C.<ref name="pmid3113259">{{cite journal | vauthors = Pollock JI, Mullin RJ | title = Vitamin C biosynthesis in prosimians: evidence for the anthropoid affinity of Tarsius | journal = American Journal of Physical Anthropology | volume = 73 | issue = 1 | pages = 65–70 | date=1987 | pmid = 3113259 | doi = 10.1002/ajpa.1330730106 }}</ref> According to molecular clock dating, these two suborder primate branches parted ways about 63 to 60 million years ago.<ref name="pmid15085543">{{cite journal | vauthors = Poux C, Douzery EJ | title = Primate phylogeny, evolutionary rate variations, and divergence times: a contribution from the nuclear gene IRBP | journal = American Journal of Physical Anthropology | volume = 124 | issue = 1 | pages = 01–16 | date=2004 | pmid = 15085543 | doi = 10.1002/ajpa.10322 }}</ref> Approximately three to five million years later (58 million years ago), only a short time afterward from an evolutionary perspective, the infraorder [[Tarsiiformes]], whose only remaining family is that of the tarsier ([[Tarsiidae]]), branched off from the other haplorrhines.<ref name="pmid9668008">{{cite journal | vauthors = Goodman M, Porter CA, Czelusniak J, Page SL, Schneider H, Shoshani J, Gunnell G, Groves CP | title = Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence | journal = Molecular Phylogenetics and Evolution | volume = 9 | issue = 3 | pages = 585–98 | date=June 1998 | pmid = 9668008 | doi = 10.1006/mpev.1998.0495 | bibcode = 1998MolPE...9..585G | s2cid = 23525774 }}</ref><ref name="Porter_1997">{{cite journal |vauthors=Porter CA, Page SL, Czelusniak J, Schneider H, Schneider MP, Sampaio I, Goodman M |s2cid=1851788 |title=Phylogeny and evolution of selected primates as determined by sequences of the ε-globin locus and 5′ flanking regions |journal=Int J Primatol |date= April 1997 |volume=18 |issue=2 |pages=261–95 |doi=10.1023/A:1026328804319 |hdl=2027.42/44561 |hdl-access=free }}</ref> Since tarsiers also cannot make vitamin C, this implies the mutation had already occurred, and thus must have occurred between these two marker points (63 to 58 million years ago).<ref name="pmid3113259" />

It has also been noted that the loss of the ability to synthesize ascorbate strikingly parallels the inability to break down [[uric acid]], also a characteristic of primates. Uric acid and ascorbate are both strong [[reducing agent]]s. This has led to the suggestion that, in higher primates, uric acid has taken over some of the functions of ascorbate.<ref name="pmid5477017">{{cite journal | vauthors = Proctor P | s2cid = 4146946 | title = Similar functions of uric acid and ascorbate in man? | journal = Nature | volume = 228 | issue = 5274 | pages = 868 | date = 1970 | pmid = 5477017 | doi = 10.1038/228868a0 | bibcode = 1970Natur.228..868P | doi-access = free | title-link = doi }}</ref>

=== Plant synthesis ===
[[File:Vitamin C Biosynthesis in Plants.svg|thumb|upright=1.75|class=skin-invert-image|Vitamin C biosynthesis in plants]]
There are many different biosynthesis pathways to ascorbic acid in plants. Most proceed through products of [[glycolysis]] and other [[metabolic pathway]]s. For example, one pathway utilizes plant [[cell wall]] polymers.<ref name="valpuesta"/> The principal plant ascorbic acid biosynthesis pathway seems to be via {{sm|l}}-galactose. The enzyme [[L-galactose 1-dehydrogenase|{{sm|l}}-galactose dehydrogenase]] catalyzes the overall [[Organic redox reaction|oxidation]] to the [[lactone]] and isomerization of the lactone to the C4-hydroxyl group, resulting in {{sm|l}}-galactono-1,4-lactone.<ref name="West Sussex 2009"/> {{sm|l}}-Galactono-1,4-lactone then reacts with the mitochondrial flavoenzyme [[Galactonolactone dehydrogenase|{{sm|l}}-galactonolactone dehydrogenase]]<ref name="pmid18190525">{{cite journal | vauthors = Leferink NG, van den Berg WA, van Berkel WJ | title = l-Galactono-gamma-lactone dehydrogenase from Arabidopsis thaliana, a flavoprotein involved in vitamin C biosynthesis | journal = The FEBS Journal | volume = 275 | issue = 4 | pages = 713–26 | date = February 2008 | pmid = 18190525 | doi = 10.1111/j.1742-4658.2007.06233.x | s2cid = 25096297 | doi-access = free | title-link = doi }}</ref> to produce ascorbic acid.<ref name="West Sussex 2009"/> {{sm|l}}-Ascorbic acid has a negative feedback on {{sm|l}}-galactose dehydrogenase in spinach.<ref name="pmid15509850">{{cite journal | vauthors = Mieda T, Yabuta Y, Rapolu M, Motoki T, Takeda T, Yoshimura K, Ishikawa T, Shigeoka S | title = Feedback inhibition of spinach L-galactose dehydrogenase by L-ascorbate | journal = Plant & Cell Physiology | volume = 45 | issue = 9 | pages = 1271–9 | date = September 2004 | pmid = 15509850 | doi = 10.1093/pcp/pch152 | doi-access = free | title-link = doi }}</ref> Ascorbic acid efflux by embryos of dicot plants is a well-established mechanism of iron reduction and a step obligatory for iron uptake.{{efn| Dicot plants transport only [[ferrous iron]] (Fe<sup>2+</sup>), but if the iron circulates as [[ferric]] complexes (Fe<sup>3+</sup>), it has to undergo a reduction before it can be actively transported. Plant embryos efflux high amounts of ascorbate that chemically reduce iron(III) from ferric complexes.<ref name="pmid24347170">{{cite journal | vauthors = Grillet L, Ouerdane L, Flis P, Hoang MT, Isaure MP, Lobinski R, Curie C, Mari S | title = Ascorbate efflux as a new strategy for iron reduction and transport in plants | journal = The Journal of Biological Chemistry | volume = 289 | issue = 5 | pages = 2515–25 | date = January 2014 | pmid = 24347170 | pmc = 3908387 | doi = 10.1074/jbc.M113.514828 | doi-access = free | title-link = doi }}</ref>}}

All plants synthesize ascorbic acid. Ascorbic acid functions as a cofactor for enzymes involved in photosynthesis, synthesis of plant hormones, as an antioxidant and regenerator of other antioxidants.<ref name=Gallie2013>{{cite journal | vauthors = Gallie DR | title = L-ascorbic acid: a multifunctional molecule supporting plant growth and development | journal = Scientifica | volume = 2013 | pages = 1–24 | year = 2013 | pmid = 24278786 | pmc = 3820358 | doi = 10.1155/2013/795964 | doi-access = free | title-link = doi }}</ref> Plants use multiple pathways to synthesize vitamin C. The major pathway starts with glucose, [[fructose]] or [[mannose]] (all simple sugars) and proceeds to {{sm|l}}-[[galactose]], {{sm|l}}-galactonolactone and ascorbic acid.<ref name=Gallie2013 /><ref name=Mellidou2017 /> This biosynthesis is regulated following a [[diurnal rhythm]].<ref name="Mellidou2017" /> Enzyme expression peaks in the morning to supporting biosynthesis for when mid-day sunlight intensity demands high ascorbic acid concentrations.<ref name=Mellidou2017>{{cite journal | vauthors = Mellidou I, Kanellis AK | title = Genetic control of ascorbic acid biosynthesis and recycling in horticultural crops | journal = Frontiers in Chemistry | volume = 5 | pages = 50 | year = 2017 | pmid = 28744455 | pmc = 5504230 | doi = 10.3389/fchem.2017.00050 | bibcode = 2017FrCh....5...50M | doi-access = free | title-link = doi }}</ref><ref name="pmid27179323">{{cite journal | vauthors = Bulley S, Laing W | title = The regulation of ascorbate biosynthesis | journal = Current Opinion in Plant Biology | volume = 33 | pages = 15–22 | date = October 2016 | pmid = 27179323 | doi = 10.1016/j.pbi.2016.04.010 | series = SI: 33: Cell signalling and gene regulation 2016 | bibcode = 2016COPB...33...15B }}</ref> Minor pathways may be specific to certain parts of plants; these can be either identical to the vertebrate pathway (including the GLO enzyme), or start with inositol and get to ascorbic acid via {{sm|l}}-galactonic acid to {{sm|l}}-galactonolactone.<ref name=Gallie2013 />

===Industrial synthesis===
{{Main|Chemistry of ascorbic acid}}
Vitamin C can be produced from [[glucose]] by two main routes. The no longer utilized [[Reichstein process]], developed in the 1930s, used a single fermentation followed by a purely chemical route. The modern two-step [[fermentation (biochemistry)|fermentation]] process, originally developed in [[China]] in the 1960s, uses additional fermentation to replace part of the later chemical stages. The Reichstein process and the modern two-step fermentation processes both use [[glucose]] as the starting material, convert that to [[sorbitol]], and then to [[sorbose]] using fermentation.<ref name="pmid23208776">{{cite journal | vauthors = Eggersdorfer M, Laudert D, Létinois U, McClymont T, Medlock J, Netscher T, Bonrath W | title = One hundred years of vitamins-a success story of the natural sciences | journal = Angewandte Chemie | volume = 51 | issue = 52 | pages = 12960–12990 | date = December 2012 | pmid = 23208776 | doi = 10.1002/anie.201205886 }}</ref> The two-step fermentation process then converts sorbose to 2-keto-l-gulonic acid (KGA) through another fermentation step, avoiding an extra intermediate. Both processes yield approximately 60% vitamin C from the glucose starting point.<ref name="Competition Commission-2001">{{cite web |url=http://www.competition-commission.org.uk/rep_pub/reports/2001/fulltext/456a4.2.pdf |archive-url=http://webarchive.nationalarchives.gov.uk/20120119194657/http://www.competition-commission.org.uk/rep_pub/reports/2001/fulltext/456a4.2.pdf |url-status=usurped |archive-date=January 19, 2012 |title=The production of vitamin C |access-date=February 20, 2007 |year=2001 |publisher=Competition Commission }}</ref> Researchers are exploring means for one-step fermentation.<ref name="pmid33717042">{{cite journal |vauthors=Zhou M, Bi Y, Ding M, Yuan Y |title=One-step biosynthesis of vitamin C in Saccharomyces cerevisiae |journal=Front Microbiol |volume=12 |issue= |pages=643472 |date=2021 |pmid=33717042 |pmc=7947327 |doi=10.3389/fmicb.2021.643472 |url= | doi-access = free | title-link = doi }}</ref><ref name="pmid35996146">{{cite journal |vauthors=Tian YS, Deng YD, Zhang WH, Yu-Wang, Xu J, Gao JJ, Bo-Wang, Fu XY, Han HJ, Li ZJ, Wang LJ, Peng RH, Yao QH |title=Metabolic engineering of Escherichia coli for direct production of vitamin C from D-glucose |journal=Biotechnol Biofuels Bioprod |volume=15 |issue=1 |pages=86 |date=August 2022 |pmid=35996146 |pmc=9396866 |doi=10.1186/s13068-022-02184-0 |url= | doi-access = free | title-link = doi |bibcode=2022BBB....15...86T }}</ref>

China produces about 70% of the global vitamin C market. The rest is split among European Union, India and North America. The global market is expected to exceed 141 thousand metric tons in 2024.<ref name="Vantage market research-2022">{{cite press release |url=https://www.globenewswire.com/en/news-release/2022/11/08/2550571/0/en/Global-Vitamin-C-Market-Size-Share-to-Surpass-1-8-Bn-by-2028-China-Produces-80-of-Commercial-Vitamin-C-Vantage-Market-Research.html |title=Vantage market research: global vitamin C market size & share to surpass $1.8 Bn by 2028 |date=November 8, 2022 |website=Globe Newswire |access-date=December 21, 2023 |archive-date=December 21, 2023 |archive-url=https://web.archive.org/web/20231221215223/https://www.globenewswire.com/en/news-release/2022/11/08/2550571/0/en/Global-Vitamin-C-Market-Size-Share-to-Surpass-1-8-Bn-by-2028-China-Produces-80-of-Commercial-Vitamin-C-Vantage-Market-Research.html |url-status=live }}</ref> Cost per metric ton (1000&nbsp;kg) in US dollars was $2,220 in Shanghai, $2,850 in Hamburg and $3,490 in the US.<ref name="ChemAnalyst-2023">{{cite web |url=https://www.chemanalyst.com/Pricing-data/vitamin-c-1258 |title=Vitamin C price trend and forecast |date=September 2023 |website=ChemAnalyst |access-date=December 21, 2023 |archive-date=December 21, 2023 |archive-url=https://web.archive.org/web/20231221215224/https://www.chemanalyst.com/Pricing-data/vitamin-c-1258 |url-status=live }}</ref>