Hydroxyproline: Difference between revisions

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Hydroxyproline differs from [[proline]] by the presence of a hydroxyl (OH) group attached to the gamma carbon atom.
Hydroxyproline differs from [[proline]] by the presence of a hydroxyl (OH) group attached to the gamma carbon atom.


[[File:Betain-Hydroxyprolin.png|thumb|right|360px|Zwitterionic structure of (2''S'',4''R'')-4-hydroxyproline (left) and (2''R'',4''S'')-4-hydroxyproline (right)]]
[[File:Betain-Hydroxyprolin.png|thumb|right|360px|Zwitterionic structure of natural (2''S'',4''R'')-4-hydroxyproline (left) and its unnatural mirror image (2''R'',4''S'')-4-hydroxyproline (right)]]


==Production and function==
==Production and function==
Hydroxyproline is produced by [[hydroxylation]] of the amino acid [[proline]] by the enzyme [[prolyl hydroxylase]] following protein synthesis (as a [[post-translational modification]]). The enzyme-catalyzed reaction takes place in the [[Lumen (anatomy)|lumen]] of the [[endoplasmic reticulum]]. Although it is not directly incorporated into proteins, hydroxyproline comprises roughly 4% of all amino acids found in animal tissue, an amount greater than seven other amino acids that are translationally incorporated.<ref name=gorres>{{cite journal |last1= Gorres |first1= Kelly L. |last2= Raines |first2= Ronald T. |date=April 2010 |title= Prolyl 4-hydroxylase |journal= Critical Reviews in Biochemistry and Molecular Biology |volume= 45 |issue= 2 |pages= 106–124 |pmc= 2841224 |doi= 10.3109/10409231003627991 |pmid= 20199358 }}</ref>
Hydroxyproline is produced by [[hydroxylation]] of the amino acid [[proline]] by the enzyme [[prolyl 4-hydroxylase]] following protein synthesis (as a [[post-translational modification]]). The enzyme-catalyzed reaction takes place in the [[Lumen (anatomy)|lumen]] of the [[endoplasmic reticulum]]. Although it is not directly incorporated into proteins, hydroxyproline comprises roughly 4% of all amino acids found in animal tissue, an amount greater than seven other amino acids that are translationally incorporated.<ref name=gorres>{{cite journal |last1= Gorres |first1= Kelly L. |last2= Raines |first2= Ronald T. |date=April 2010 |title= Prolyl 4-hydroxylase |journal= Critical Reviews in Biochemistry and Molecular Biology |volume= 45 |issue= 2 |pages= 106–124 |pmc= 2841224 |doi= 10.3109/10409231003627991 |pmid= 20199358 }}</ref>


=== Animals ===
=== Animals ===


==== Collagen ====
==== Collagen ====
Hydroxyproline is a major component of the [[protein]] [[collagen]],<ref name="SzpakJAS">{{Cite journal |last=Szpak |first=Paul |title=Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis | url=https://www.academia.edu/801925 |journal=[[Journal of Archaeological Science]] |year=2011 |volume=38 |issue=12 |pages=3358–3372 |doi=10.1016/j.jas.2011.07.022 }}</ref> comprising roughly 13.5% of mammalian collagen. Hydroxyproline and proline play key roles for collagen stability.<ref name="Nelson">Nelson, D. L. and Cox, M. M. (2005) Lehninger's Principles of Biochemistry, 4th Edition, W. H. Freeman and Company, New York.</ref> They permit the sharp twisting of the collagen helix.<ref name="Brinckmann">Brinckmann, J., Notbohm, H. and Müller, P.K. (2005) Collagen, Topics in Current Chemistry 247, Springer, Berlin.</ref> In the canonical collagen Xaa-Yaa-Gly triad (where Xaa and Yaa are any amino acid), a proline occupying the Yaa position is hydroxylated to give a Xaa-Hyp-Gly sequence.  This modification of the proline residue increases the stability of the collagen [[triple helix]]. It was initially proposed that the stabilization was due to water molecules forming a hydrogen bonding network linking the prolyl hydroxyl groups and the main-chain carbonyl groups.<ref name="Bella1994">{{cite journal | last1 = Bella | first1 = J | last2 = Eaton | first2 = M | last3 = Brodsky | first3 = B | last4 = Berman | first4 = HM | title = Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution | journal = Science | volume = 266 | issue = 5182 | pages = 75–81 | year = 1994 | pmid = 7695699 | doi=10.1126/science.7695699}}</ref> It was subsequently shown that the increase in stability is primarily through [[stereoelectronic effect]]s and that hydration of the hydroxyproline residues provides little or no additional stability.<ref name="Kotch2008">{{cite journal | doi = 10.1021/ja800225k | last1 = Kotch | first1 = F.W. | last2 = Guzei | first2 = I.A. | last3 = Raines | first3 = R.T. | year = 2008 | title = Stabilization of the Collagen Triple Helix by O-Methylation of Hydroxyproline Residues | journal = Journal of the American Chemical Society | volume = 130 | issue = 10| pages = 2952–2953 | pmid = 18271593 | pmc = 2802593 }}</ref>
Hydroxyproline is a major component of the [[protein]] [[collagen]],<ref name="SzpakJAS">{{Cite journal |last=Szpak |first=Paul |title=Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis | url=https://www.academia.edu/801925 |journal=[[Journal of Archaeological Science]] |year=2011 |volume=38 |issue=12 |pages=3358–3372 |doi=10.1016/j.jas.2011.07.022 |bibcode=2011JArSc..38.3358S }}</ref> comprising roughly 13.5% of mammalian collagen. Hydroxyproline and proline play key roles for collagen stability.<ref name="Nelson">Nelson, D. L. and Cox, M. M. (2005) Lehninger's Principles of Biochemistry, 4th Edition, W. H. Freeman and Company, New York.</ref> They permit the sharp twisting of the collagen helix.<ref name="Brinckmann">Brinckmann, J., Notbohm, H. and Müller, P.K. (2005) Collagen, Topics in Current Chemistry 247, Springer, Berlin.</ref> In the canonical collagen Xaa-Yaa-Gly triad (where Xaa and Yaa are any amino acid), a proline occupying the Yaa position is hydroxylated to give a Xaa-Hyp-Gly sequence.  This modification of the proline residue increases the stability of the collagen [[triple helix]]. It was initially proposed that the stabilization was due to water molecules forming a hydrogen bonding network linking the prolyl hydroxyl groups and the main-chain carbonyl groups.<ref name="Bella1994">{{cite journal | last1 = Bella | first1 = J | last2 = Eaton | first2 = M | last3 = Brodsky | first3 = B | last4 = Berman | first4 = HM | title = Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution | journal = Science | volume = 266 | issue = 5182 | pages = 75–81 | year = 1994 | pmid = 7695699 | doi=10.1126/science.7695699}}</ref> It was subsequently shown that the increase in stability is primarily through [[stereoelectronic effect]]s and that hydration of the hydroxyproline residues provides little or no additional stability.<ref name="Kotch2008">{{cite journal | doi = 10.1021/ja800225k | last1 = Kotch | first1 = F.W. | last2 = Guzei | first2 = I.A. | last3 = Raines | first3 = R.T. | year = 2008 | title = Stabilization of the Collagen Triple Helix by O-Methylation of Hydroxyproline Residues | journal = Journal of the American Chemical Society | volume = 130 | issue = 10| pages = 2952–2953 | pmid = 18271593 | pmc = 2802593 | bibcode = 2008JAChS.130.2952K }}</ref>


==== Non-collagen ====
==== Non-collagen ====
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Hydroxylation of proline has been shown to be involved in targeting [[Hypoxia-inducible factor]] (HIF) alpha subunit ([[HIF-1 alpha]]) for degradation by [[proteolysis]]. Under [[normoxia]] (normal oxygen conditions) [[EGLN1]][https://www.ncbi.nlm.nih.gov/gene/54583] protein hydroxylates the proline at the 564 position of HIF-1 alpha, which allows [[ubiquitylation]] by the [[von Hippel-Lindau tumor suppressor]] (pVHL) and subsequent targeting for [[proteasome]] degradation.<ref name="Jaakkola">{{cite journal | doi = 10.1126/science.1059796 | last1 = Jaakkola | first1 = P. | last2 = Mole | first2 = D.R. | last3 = Tian | first3 = Y.M. | last4 = Wilson | first4 = M.I. | last5 = Gielbert | first5 = J. | last6 = Gaskell | first6 = S.J. | last7 = Kriegsheim | first7 = A.V. | last8 = Hebestreit | first8 = H.F. | last9 = Mukherji | first9 = M. | last10 = Schofield | first10 = C. J. | last11 = Maxwell | first11 = P. H. | last12 = Pugh | first12 = C. W. | last13 = Ratcliffe | first13 = P. J. | year = 2001 | title = Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation | journal = Science | volume = 292 | issue = 5516| pages = 468–72 | pmid = 11292861 | bibcode = 2001Sci...292..468J | s2cid = 20914281 | display-authors = 8 | doi-access = free }}</ref>
Hydroxylation of proline has been shown to be involved in targeting [[Hypoxia-inducible factor]] (HIF) alpha subunit ([[HIF-1 alpha]]) for degradation by [[proteolysis]]. Under [[normoxia]] (normal oxygen conditions) [[EGLN1]][https://www.ncbi.nlm.nih.gov/gene/54583] protein hydroxylates the proline at the 564 position of HIF-1 alpha, which allows [[ubiquitylation]] by the [[von Hippel-Lindau tumor suppressor]] (pVHL) and subsequent targeting for [[proteasome]] degradation.<ref name="Jaakkola">{{cite journal | doi = 10.1126/science.1059796 | last1 = Jaakkola | first1 = P. | last2 = Mole | first2 = D.R. | last3 = Tian | first3 = Y.M. | last4 = Wilson | first4 = M.I. | last5 = Gielbert | first5 = J. | last6 = Gaskell | first6 = S.J. | last7 = Kriegsheim | first7 = A.V. | last8 = Hebestreit | first8 = H.F. | last9 = Mukherji | first9 = M. | last10 = Schofield | first10 = C. J. | last11 = Maxwell | first11 = P. H. | last12 = Pugh | first12 = C. W. | last13 = Ratcliffe | first13 = P. J. | year = 2001 | title = Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation | journal = Science | volume = 292 | issue = 5516| pages = 468–72 | pmid = 11292861 | bibcode = 2001Sci...292..468J | s2cid = 20914281 | display-authors = 8 | doi-access = free }}</ref>
[[DYRK1A]], [[DYRK1B]], [[protein kinase B]], [[eEF2]], [[IKK2]], [[p53]], [[FOXO3A]], [[CEP192]] are also reportedly hydroxylated by [[PHD1]]. p53 and [[MAPH6]] are also hydroxylated by PHD3.<ref name="Hu22"/>
Free hydroxyproline appears to be an antioxidant, like free proline.<ref name="Hu22"/>


=== Plants ===
=== Plants ===
Hydroxyproline rich [[glycoprotein]]s (HRGPs) are also found in [[plant cell walls]].<ref name=":0">{{cite journal | doi = 10.1146/annurev.arplant.49.1.281| pmid = 15012236| title = Plant Cell Wall Proteins| journal = Annual Review of Plant Physiology and Plant Molecular Biology| volume = 49| pages = 281–309| year = 1998| last1 = Cassab| first1 = Gladys I}}</ref> These hydroxyprolines serve as the attachment points for [[Glycan|glycan chains]] which are added as [[Post-translational modification|post-translational modifications]].<ref name=":0" />
Hydroxyproline rich [[glycoprotein]]s (HRGPs) are also found in [[plant cell walls]].<ref name=":0">{{cite journal | doi = 10.1146/annurev.arplant.49.1.281| pmid = 15012236| title = Plant Cell Wall Proteins| journal = Annual Review of Plant Physiology and Plant Molecular Biology| volume = 49| pages = 281–309| year = 1998| last1 = Cassab| first1 = Gladys I}}</ref> These hydroxyprolines serve as the attachment points for [[Glycan|glycan chains]] which are added as [[Post-translational modification|post-translational modifications]].<ref name=":0" />
=== Protists ===
Hydroxyproline is also found in the walls of [[oomycete]]s, fungus-like protists related to diatoms.<ref name="Alexopoulos 1996">{{Cite book | author = Alexopoulos, C.J., Mims C.W. and Blackwell, M. | year = 1996 | title = Introductory Mycology | edition = 4th | pages = 687–688 | location = New York | publisher = John Wiley & Sons | isbn = 978-0-471-52229-4}}</ref> ''[[Phytophthora cactorum]]'' specifically produces a pathogenic protein containg 4-hydroxyproline.<ref>{{cite journal |last1=Orsomando |first1=Giuseppe |last2=Lorenzi |first2=Maria |last3=Raffaelli |first3=Nadia |last4=Dalla Rizza |first4=Marco |last5=Mezzetti |first5=Bruno |last6=Ruggieri |first6=Silverio |title=Phytotoxic Protein PcF, Purification, Characterization, and cDNA Sequencing of a Novel Hydroxyproline-containing Factor Secreted by the Strawberry Pathogen Phytophthora cactorum |journal=Journal of Biological Chemistry |date=June 2001 |volume=276 |issue=24 |pages=21578–21584 |doi=10.1074/jbc.M101377200|doi-access=free |pmid=11262411 }}</ref>
== Catabolism ==
Free 4-hydroxyproline is produced when collagen is broken down. Two possible pathways can be used to break it down: the [[hydroxyproline dehydrogenase]] (PRODH2) pathway results in the production of glycine, glyoxylate, glycolate, and oxalate, while the [[L-amino-acid oxidase]] pathway results in the production of [[pyrrole-2-carboxylate]]. This additional source of glycine is important in young livestock as mammal milk and plant-based feed is deficient in glycine.<ref name="Hu22"/>


==Clinical significance==
==Clinical significance==
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Increased serum and urine levels of hydroxyproline have also been demonstrated in [[Paget's disease of bone|Paget's disease]].<ref>{{cite web|url=http://www.wheelessonline.com/ortho/pagets_disease|title=Wheeless' Textbook of Orthopaedics|website=Wheeless Online|date=22 July 2020}}</ref>
Increased serum and urine levels of hydroxyproline have also been demonstrated in [[Paget's disease of bone|Paget's disease]].<ref>{{cite web|url=http://www.wheelessonline.com/ortho/pagets_disease|title=Wheeless' Textbook of Orthopaedics|website=Wheeless Online|date=22 July 2020}}</ref>


[[Mass spectrometry]] analysis showed decreased amount of hydroxyproline [[post-translational modifications]] in non inflamed tissue from [[ulcerative colitis]] patients when compared to tissue from donors without the disease. <ref>{{cite web|url=https://pubs.rsc.org/en/content/articlelanding/2019/mo/c8mo00239h|title=Degradation of the extracellular matrix is part of the pathology of ulcerative colitis}}</ref>
[[Mass spectrometry]] analysis showed decreased amount of hydroxyproline [[post-translational modifications]] in non inflamed tissue from [[ulcerative colitis]] patients when compared to tissue from donors without the disease. <ref>{{cite journal|url=https://pubs.rsc.org/en/content/articlelanding/2019/mo/c8mo00239h|title=Degradation of the extracellular matrix is part of the pathology of ulcerative colitis|date=2019 |doi=10.1039/C8MO00239H |last1=Kirov |first1=Stefan |last2=Sasson |first2=Ariella |last3=Zhang |first3=Clarence |last4=Chasalow |first4=Scott |last5=Dongre |first5=Ashok |last6=Steen |first6=Hanno |last7=Stensballe |first7=Allan |last8=Andersen |first8=Vibeke |last9=Birkelund |first9=Svend |last10=Bennike |first10=Tue Bjerg |journal=Molecular Omics |volume=15 |pages=67–76 |pmid=30702115 }}</ref>


==Other hydroxyprolines==
==Other hydroxyprolines==
Other hydroxyprolines also exist in nature. The most notable ones are 2,3-''cis''-, 3,4-''trans''-, and 3,4-dihydroxyproline, which occurs in [[diatom]] [[cell wall]]s<ref name="Nakajima">{{cite journal | doi = 10.1126/science.164.3886.1400 | last1 = Nakajima | first1 = T. | last2 = Volcani | first2 = B.E. | year = 1969 | title = 3,4-Dihydroxyproline: a new amino acid in diatom cell walls | journal = Science | volume = 164 | issue = 3886| pages = 1400–1401 | pmid = 5783709 | bibcode = 1969Sci...164.1400N | s2cid = 23673503 }}</ref> and are postulated to have a role in [[silica]] deposition.  Hydroxyproline is also found in the walls of [[oomycete]]s, fungus-like protists related to diatoms.<ref name="Alexopoulos 1996">{{Cite book | author = Alexopoulos, C.J., Mims C.W. and Blackwell, M. | year = 1996 | title = Introductory Mycology | edition = 4th | pages = 687–688 | location = New York | publisher = John Wiley & Sons | isbn = 978-0-471-52229-4}}</ref> (2''S'',4''S'')-''cis''-4-Hydroxyproline is found in the toxic [[cyclic peptide]]s from ''[[Amanita]]'' mushrooms (''e.g.'', [[phalloidin]]).<ref>{{cite book | author = Wieland, T. | title = Peptides of Poisonous Amanita Mushrooms | publisher = Springer | year = 1986}}</ref>
<!-- Notable begins with occurring in humans! -->
=== Isomers ===
Other hydroxyprolines also exist in nature. The most notable one is ''trans''-L-3-hydroxyproline (or (2S,3S)-3-hydroxyproline), produced in humans and other animals by [[prolyl 3-hydroxylase]] ([[EC 1.14.11.7]]).<ref name="Hu22">{{cite journal |last1=Hu |first1=Shengdi |last2=He |first2=Wenliang |last3=Wu |first3=Guoyao |title=Hydroxyproline in animal metabolism, nutrition, and cell signaling |journal=Amino Acids |date=April 2022 |volume=54 |issue=4 |pages=513–528 |doi=10.1007/s00726-021-03056-x|pmid=34342708 }}</ref> Although present in much lower amounts than ''trans''-L-4-hydroxyproline, 3-hydroxyproline is indispensable for the functioning of [[type IV collagen]] in mice. Without it the embryo does not survive to birth.<ref>{{cite journal |last1=Pokidysheva |first1=Elena |last2=Boudko |first2=Sergei |last3=Vranka |first3=Janice |last4=Zientek |first4=Keith |last5=Maddox |first5=Kerry |last6=Moser |first6=Markus |last7=Fässler |first7=Reinhard |last8=Ware |first8=Jerry |last9=Bächinger |first9=Hans Peter |title=Biological role of prolyl 3-hydroxylation in type IV collagen |journal=Proceedings of the National Academy of Sciences |date=7 January 2014 |volume=111 |issue=1 |pages=161–166 |doi=10.1073/pnas.1307597111|doi-access=free |bibcode=2014PNAS..111..161P }}</ref>
 
Intestinal bacteria produce [[4-hydroxyproline epimerase]], which performs a bidirectional conversion between the typical (for humans) ''trans''-4-hydroxyproline and ''cis''-4-hydroxy-D-proline. Archaea, trypanosomes, and possibly animals also perform this conversion. <ref name="Hu22"/>
 
''cis''-4-Hydroxyproline (equivalently, (2''S'',4''S'')-) is found in the toxic [[cyclic peptide]]s from ''[[Amanita]]'' mushrooms (''e.g.'', [[phalloidin]]).<ref>{{cite book | author = Wieland, T. | title = Peptides of Poisonous Amanita Mushrooms | publisher = Springer | year = 1986}}</ref>
 
=== Further modifications ===
[[Diatom]] [[cell wall]]s contain 2,3-''cis''-, 3,4-''trans''-, and 3,4-dihydroxyproline, which are postulated to have a role in [[silica]] deposition.<ref name="Nakajima">{{cite journal | doi = 10.1126/science.164.3886.1400 | last1 = Nakajima | first1 = T. | last2 = Volcani | first2 = B.E. | year = 1969 | title = 3,4-Dihydroxyproline: a new amino acid in diatom cell walls | journal = Science | volume = 164 | issue = 3886| pages = 1400–1401 | pmid = 5783709 | bibcode = 1969Sci...164.1400N | s2cid = 23673503 }}</ref>


==See also==
==See also==

Latest revision as of 18:53, 10 June 2025

Template:Chembox

(2S,4R)-4-Hydroxyproline, or L-hydroxyproline (C5H9O3N), is an amino acid, abbreviated as Hyp or O, e.g., in Protein Data Bank.

Structure and discovery

In 1902, Hermann Emil Fischer isolated hydroxyproline from hydrolyzed gelatin. In 1905, Hermann Leuchs synthesized a racemic mixture of 4-hydroxyproline.[1]

Hydroxyproline differs from proline by the presence of a hydroxyl (OH) group attached to the gamma carbon atom.

File:Betain-Hydroxyprolin.png
Zwitterionic structure of natural (2S,4R)-4-hydroxyproline (left) and its unnatural mirror image (2R,4S)-4-hydroxyproline (right)

Production and function

Hydroxyproline is produced by hydroxylation of the amino acid proline by the enzyme prolyl 4-hydroxylase following protein synthesis (as a post-translational modification). The enzyme-catalyzed reaction takes place in the lumen of the endoplasmic reticulum. Although it is not directly incorporated into proteins, hydroxyproline comprises roughly 4% of all amino acids found in animal tissue, an amount greater than seven other amino acids that are translationally incorporated.[2]

Animals

Collagen

Hydroxyproline is a major component of the protein collagen,[3] comprising roughly 13.5% of mammalian collagen. Hydroxyproline and proline play key roles for collagen stability.[4] They permit the sharp twisting of the collagen helix.[5] In the canonical collagen Xaa-Yaa-Gly triad (where Xaa and Yaa are any amino acid), a proline occupying the Yaa position is hydroxylated to give a Xaa-Hyp-Gly sequence. This modification of the proline residue increases the stability of the collagen triple helix. It was initially proposed that the stabilization was due to water molecules forming a hydrogen bonding network linking the prolyl hydroxyl groups and the main-chain carbonyl groups.[6] It was subsequently shown that the increase in stability is primarily through stereoelectronic effects and that hydration of the hydroxyproline residues provides little or no additional stability.[7]

Non-collagen

Hydroxyproline is found in few proteins other than collagen. For this reason, hydroxyproline content has been used as an indicator to determine collagen and/or gelatin amount. However, the mammalian proteins elastin and argonaute 2 have collagen-like domains in which hydroxyproline is formed. Some snail poisons, conotoxins, contain hydroxyproline, but lack collagen-like sequences.[2]

Hydroxylation of proline has been shown to be involved in targeting Hypoxia-inducible factor (HIF) alpha subunit (HIF-1 alpha) for degradation by proteolysis. Under normoxia (normal oxygen conditions) EGLN1[1] protein hydroxylates the proline at the 564 position of HIF-1 alpha, which allows ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) and subsequent targeting for proteasome degradation.[8]

DYRK1A, DYRK1B, protein kinase B, eEF2, IKK2, p53, FOXO3A, CEP192 are also reportedly hydroxylated by PHD1. p53 and MAPH6 are also hydroxylated by PHD3.[9]

Free hydroxyproline appears to be an antioxidant, like free proline.[9]

Plants

Hydroxyproline rich glycoproteins (HRGPs) are also found in plant cell walls.[10] These hydroxyprolines serve as the attachment points for glycan chains which are added as post-translational modifications.[10]

Protists

Hydroxyproline is also found in the walls of oomycetes, fungus-like protists related to diatoms.[11] Phytophthora cactorum specifically produces a pathogenic protein containg 4-hydroxyproline.[12]

Catabolism

Free 4-hydroxyproline is produced when collagen is broken down. Two possible pathways can be used to break it down: the hydroxyproline dehydrogenase (PRODH2) pathway results in the production of glycine, glyoxylate, glycolate, and oxalate, while the L-amino-acid oxidase pathway results in the production of pyrrole-2-carboxylate. This additional source of glycine is important in young livestock as mammal milk and plant-based feed is deficient in glycine.[9]

Clinical significance

Proline hydroxylation requires ascorbic acid (vitamin C). The most obvious, first effects (gingival and hair problems) of absence of ascorbic acid in humans come from the resulting defect in hydroxylation of proline residues of collagen, with reduced stability of the collagen molecule, causing scurvy.

Increased serum and urine levels of hydroxyproline have also been demonstrated in Paget's disease.[13]

Mass spectrometry analysis showed decreased amount of hydroxyproline post-translational modifications in non inflamed tissue from ulcerative colitis patients when compared to tissue from donors without the disease. [14]

Other hydroxyprolines

Isomers

Other hydroxyprolines also exist in nature. The most notable one is trans-L-3-hydroxyproline (or (2S,3S)-3-hydroxyproline), produced in humans and other animals by prolyl 3-hydroxylase (EC 1.14.11.7).[9] Although present in much lower amounts than trans-L-4-hydroxyproline, 3-hydroxyproline is indispensable for the functioning of type IV collagen in mice. Without it the embryo does not survive to birth.[15]

Intestinal bacteria produce 4-hydroxyproline epimerase, which performs a bidirectional conversion between the typical (for humans) trans-4-hydroxyproline and cis-4-hydroxy-D-proline. Archaea, trypanosomes, and possibly animals also perform this conversion. [9]

cis-4-Hydroxyproline (equivalently, (2S,4S)-) is found in the toxic cyclic peptides from Amanita mushrooms (e.g., phalloidin).[16]

Further modifications

Diatom cell walls contain 2,3-cis-, 3,4-trans-, and 3,4-dihydroxyproline, which are postulated to have a role in silica deposition.[17]

See also

References

Template:Reflist

External links

Template:Non-proteinogenic amino acids

  1. ↑ Script error: No such module "citation/CS1".
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  4. ↑ Nelson, D. L. and Cox, M. M. (2005) Lehninger's Principles of Biochemistry, 4th Edition, W. H. Freeman and Company, New York.
  5. ↑ Brinckmann, J., Notbohm, H. and Müller, P.K. (2005) Collagen, Topics in Current Chemistry 247, Springer, Berlin.
  6. ↑ Script error: No such module "Citation/CS1".
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  16. ↑ Script error: No such module "citation/CS1".
  17. ↑ Script error: No such module "Citation/CS1".
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