Editing Vitamin C (section)

==Pharmacology==
{{See also|Chemistry of ascorbic acid}}

[[Pharmacodynamics]] is the study of how the drug – in this instance vitamin C – affects the organism, whereas [[pharmacokinetics]] is the study of how an organism affects the drug.

===Pharmacodynamics===
Pharmacodynamics includes enzymes for which vitamin C is a cofactor, with function potentially compromised in a deficiency state, and any enzyme cofactor or other physiological function affected by administration of vitamin C, orally or injected, in excess of normal requirements. At normal physiological concentrations, vitamin C serves as an [[enzyme]] [[substrate (biochemistry)|substrate]] or [[cofactor (biochemistry)|cofactor]] and an [[electron donor]] antioxidant. The enzymatic functions include the synthesis of [[collagen]], [[carnitine]], and [[neurotransmitter]]s; the synthesis and [[catabolism]] of [[tyrosine]]; and the metabolism of [[microsome]]s. In nonenzymatic functions it acts as a reducing agent, donating electrons to oxidized molecules and preventing oxidation in order to keep iron and copper atoms in their reduced states.<ref name=PKIN2020VitC/> At non-physiological concentrations achieved by intravenous dosing, vitamin C may function as a [[pro-oxidant]], with therapeutic toxicity against cancer cells.<ref name="Bottger2021">{{cite journal |vauthors=Böttger F, Vallés-Martí A, Cahn L, Jimenez CR |title=High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer |journal=J Exp Clin Cancer Res |volume=40 |issue=1 |pages=343 |date=October 2021 |pmid=34717701 |pmc=8557029 |doi=10.1186/s13046-021-02134-y |doi-access=free |url=}}</ref><ref name="Park2018">{{cite journal |vauthors=Park S, Ahn S, Shin Y, Yang Y, Yeom CH |title=Vitamin C in cancer: a metabolomics perspective |journal=Front Physiol |volume=9 |issue= |pages=762 |date=2018 |pmid=29971019 |pmc=6018397 |doi=10.3389/fphys.2018.00762 |doi-access=free |url=}}</ref>

Vitamin C functions as a cofactor for the following [[enzyme]]s:<ref name=PKIN2020VitC/>
* Three groups of enzymes ([[prolyl-3-hydroxylase]]s, [[P4HA1|prolyl-4-hydroxylase]]s, and [[lysyl hydroxylase]]s) that are required for the [[hydroxylation]] of [[proline]] and [[lysine]] in the synthesis of [[collagen]]. These reactions add [[hydroxide|hydroxyl groups]] to the amino acids [[proline]] or [[lysine]] in the collagen molecule via [[prolyl hydroxylase]] and [[lysyl hydroxylase]], both requiring vitamin C as a [[cofactor (biochemistry)|cofactor]]. The role of vitamin C as a cofactor is to oxidize prolyl hydroxylase and lysyl hydroxylase from Fe{{sup|2+}} to Fe{{sup|3+}} and to reduce it from Fe{{sup|3+}} to Fe{{sup|2+}}. Hydroxylation allows the collagen molecule to assume its triple [[helix]] structure, and thus vitamin C is essential to the development and maintenance of [[granulation tissue|scar tissue]], [[blood vessel]]s, and [[cartilage]].
* Two enzymes ([[trimethyllysine dioxygenase|ε-N-trimethyl-L-lysine hydroxylase]] and [[gamma-butyrobetaine dioxygenase|γ-butyrobetaine hydroxylase]]) are necessary for synthesis of [[carnitine]]. Carnitine is essential for the transport of [[fatty acid]]s into [[mitochondria]] for [[Adenosine triphosphate|ATP]] generation.
* [[Hypoxia-inducible factor-proline dioxygenase]] enzymes (isoforms: [[EGLN1]], [[EGLN2]], and [[EGLN3]]) allows cells to respond physiologically to low concentrations of oxygen.
* [[Dopamine beta-hydroxylase]] participates in the biosynthesis of [[norepinephrine]] from [[dopamine]].
* [[Peptidylglycine alpha-amidating monooxygenase]] amidates [[peptide hormone]]s by removing the glyoxylate residue from their c-terminal glycine residues. This increases peptide hormone stability and activity.

As an antioxidant, ascorbate scavenges reactive oxygen and nitrogen compounds, thus neutralizing the potential tissue damage of these [[free radical]] compounds. Dehydroascorbate, the oxidized form, is then recycled back to ascorbate by endogenous antioxidants such as [[glutathione]].<ref name=DRItext />{{rp|pages=98–99}} In the eye, ascorbate is thought to protect against photolytically generated free-radical damage; higher plasma ascorbate is associated with lower risk of cataracts.<ref name="pmid30878580"/> Ascorbate may also provide antioxidant protection indirectly by regenerating other biological antioxidants such as [[α-tocopherol]] back to an active state.<ref name=DRItext />{{rp|pages=98–99}} In addition, ascorbate also functions as a non-enzymatic reducing agent for mixed-function oxidases in the microsomal drug-metabolizing system that inactivates a wide variety of substrates such as drugs and environmental carcinogens.<ref name=DRItext />{{rp|pages=98–99}}

===Pharmacokinetics===
Ascorbic acid is absorbed in the body by both active transport and passive diffusion.<ref>{{cite journal |vauthors=Lykkesfeldt J, Tveden-Nyborg P |title=The pharmacokinetics of vitamin C |journal=Nutrients |volume=11 |issue=10 |date=October 2019 |page=2412 |pmid=31601028 |pmc=6835439 |doi=10.3390/nu11102412 |doi-access=free |url=}}</ref> Approximately 70%–90% of vitamin C is active-transport absorbed when intakes of 30–180&nbsp;mg/day from a combination of food sources and moderate-dose dietary supplements such as a multi-vitamin/mineral product are consumed. However, when large amounts are consumed, such as a vitamin C dietary supplement, the active transport system becomes saturated, and while the total amount being absorbed continues to increase with dose, absorption efficiency falls to less than 50%.<ref name=NIH2021 /> Active transport is managed by Sodium-Ascorbate Co-Transporter proteins (SVCTs) and Hexose Transporter proteins (GLUTs). [[SLC23A1|SVCT1]] and [[SLC23A2|SVCT2]] import ascorbate across plasma membranes.<ref name="Savini_2008">{{cite journal | vauthors = Savini I, Rossi A, Pierro C, Avigliano L, Catani MV | title = SVCT1 and SVCT2: key proteins for vitamin C uptake | journal = Amino Acids | volume = 34 | issue = 3 | pages = 347–55 | date = April 2008 | pmid = 17541511 | doi = 10.1007/s00726-007-0555-7 | s2cid = 312905 }}</ref> The Hexose Transporter proteins [[GLUT1]], [[GLUT3]] and [[GLUT4]] transfer only the oxydized dehydroascorbic acid (DHA) form of vitamin C.<ref name="pmid9228080">{{cite journal | vauthors = Rumsey SC, Kwon O, Xu GW, Burant CF, Simpson I, Levine M | title = Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid | journal = The Journal of Biological Chemistry | volume = 272 | issue = 30 | pages = 18982–9 | date = July 1997 | pmid = 9228080 | doi = 10.1074/jbc.272.30.18982 | doi-access = free | title-link = doi }}</ref><ref name=Linster2007 /> The amount of DHA found in plasma and tissues under normal conditions is low, as cells rapidly reduce DHA to ascorbate.<ref name="pmid12729925">{{cite journal | vauthors = May JM, Qu ZC, Neel DR, Li X | title = Recycling of vitamin C from its oxidized forms by human endothelial cells | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1640 | issue = 2–3 | pages = 153–61 | date = May 2003 | pmid = 12729925 | doi = 10.1016/S0167-4889(03)00043-0 | doi-access =  | title-link = doi }}</ref>

SVCTs are the predominant system for vitamin C transport within the body.<ref name="Savini_2008" /> In both vitamin C synthesizers (example: rat) and non-synthesizers (example: human) cells maintain ascorbic acid concentrations much higher than the approximately 50 micromoles/liter (μmol/L) found in plasma. For example, the ascorbic acid content of pituitary and adrenal glands can exceed 2,000&nbsp;μmol/L, and muscle is at 200–300&nbsp;μmol/L.<ref name=Padayatty2016>{{cite journal | vauthors = Padayatty SJ, Levine M | title = Vitamin C: the known and the unknown and Goldilocks | journal = Oral Diseases | volume = 22 | issue = 6 | pages = 463–93 | date = September 2016 | pmid = 26808119 | pmc = 4959991 | doi = 10.1111/odi.12446 }}</ref> The known coenzymatic functions of ascorbic acid do not require such high concentrations, so there may be other, as yet unknown functions. A consequence of all this high concentration organ content is that plasma vitamin C is not a good indicator of whole-body status, and people may vary in the amount of time needed to show symptoms of deficiency when consuming a diet very low in vitamin C.<ref name=Padayatty2016 />

Excretion (via urine) is as ascorbic acid and metabolites. The fraction that is excreted as unmetabolized ascorbic acid increases as intake increases. In addition, ascorbic acid converts (reversibly) to DHA and from that compound non-reversibly to 2,3-diketogulonate and then oxalate. These three metabolites are also excreted via urine. During times of low dietary intake, vitamin C is reabsorbed by the kidneys rather than excreted. This salvage process delays onset of deficiency. Humans are better than guinea pigs at converting DHA back to ascorbate, and thus take much longer to become vitamin C deficient.<ref name=PKIN2020VitC/><ref name=Linster2007 />