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Revision as of 13:09, 19 March 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{chembox}} (no changed fields - added verified revid - updated 'UNII_Ref', 'ChemSpiderID_Ref', 'StdInChI_Ref', 'StdInChIKey_Ref', 'ChEMBL_Ref', 'KEGG_Ref') per Chem/Drugbox validation (← Previous edit		Latest revision as of 00:02, 26 October 2023 edit undoRandy Kryn (talk | contribs)Extended confirmed users286,167 edits →Biological function: uppercase per proper name and Misplaced Pages style (Earth), link
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	{{distinguish|ferrochrome}}		{{distinguish|ferrochrome}}
			{{for|the audio tape formulation|Compact Cassette tape types and formulations#Ferrichrome}}
	{{chembox		{{chembox
	| verifiedrevid = 413080277		| verifiedrevid = 419621860
	|ImageFile=ferrichrome.png		| ImageFile=ferrichrome.png
	|ImageSize=200px		| ImageSize=200px
			| ImageCaption=Ferrichrome (sticks) bound to an iron atom (orange)
	|IUPACName=''N''-propyl]-2,5,8,11,14,17-hexaoxo-3,6,9,12,15,18-hexazacyclooctadec-1-yl]propyl]-''N''-oxidoacetamide; iron(3+)		| IUPACName=''N''-propyl]-2,5,8,11,14,17-hexaoxo-3,6,9,12,15,18-hexazacyclooctadec-1-yl]propyl]-''N''-oxidoacetamide; iron(3+)
	|OtherNames=		| OtherNames=
	|Section1={{Chembox Identifiers		|Section1={{Chembox Identifiers
			| CASNo_Ref = {{cascite|correct|ECHA}}
	| CASNo=15630-64-5		| CASNo=15630-64-5
⚫	| PubChem=27424
			| UNII_Ref = {{fdacite|correct|FDA}}
⚫	| SMILES=CC(=O)N(CCCC1C(=O)NC(C(=O)NC(C(=O)NCC(=O)NCC(=O)NCC(=O)N1)CCCN(C(=O)C))CCCN(C(=O)C)).
			| UNII = G884EC9X73
		⚫	| PubChem=27424
			| EINECS=239-706-0
			| ChemSpiderID = 26333219
			| StdInChI=1S/C27H42N9O12.Fe/c1-16(37)34(46)10-4-7-19-25(43)30-14-23(41)28-13-22(40)29-15-24(42)31-20(8-5-11-35(47)17(2)38)26(44)33-21(27(45)32-19)9-6-12-36(48)18(3)39;/h19-21H,4-15H2,1-3H3,(H,28,41)(H,29,40)(H,30,43)(H,31,42)(H,32,45)(H,33,44);/q-3;+3
			| StdInChIKey = GGUNGDGGXMHBMJ-UHFFFAOYSA-N
		⚫	| SMILES=CC(=O)N(CCCC1C(=O)NC(C(=O)NC(C(=O)NCC(=O)NCC(=O)NCC(=O)N1)CCCN(C(=O)C))CCCN(C(=O)C)).
	}}		}}
	|Section2={{Chembox Properties		|Section2={{Chembox Properties
			| C=27 | H=42 | Fe=1 | N=9 | O=12
	| Formula=C<sub>27</sub>H<sub>42</sub>FeN<sub>9</sub>O<sub>12</sub>
			| Appearance=
	| MolarMass=740.52 g/mol
	| Appearance=		| Density=
	| Density=		| MeltingPt=
	| MeltingPt=		| BoilingPt=
	| BoilingPt=		| Solubility=
	| Solubility=
	}}		}}
	|Section3={{Chembox Hazards		|Section3={{Chembox Hazards
	| MainHazards=		| MainHazards=
	| FlashPt=		| FlashPt=
			| AutoignitionPt =
	| Autoignition=
	}}		}}
	}}		}}
	'''Ferrichrome''' is a cyclic hexa-] that forms a complex with iron atoms.		'''Ferrichrome''' is a cyclic hexa-] that forms a complex with iron atoms. It is a ] composed of three glycine and three modified ornithine residues with hydroxamate groups . The 6 oxygen atoms from the three hydroxamate groups bind Fe(III) in near perfect octahedral coordination.
	Ferrichrome was first isolated in 1952, has been found to be produced by ] of the genera '']'', '']'', and '']''.<ref>, Virtual Museum of Minerals and Molecules, University of Wisconsin</ref>		Ferrichrome was first isolated in 1952, and has been found to be produced by ] of the genera '']'', '']'', and '']''.<ref> {{Webarchive|url=https://web.archive.org/web/20100113205159/http://virtual-museum.soils.wisc.edu/ferrichrome/index.html |date=2010-01-13 }}, Virtual Museum of Minerals and Molecules, University of Wisconsin</ref> However, at the time there was no understanding regarding its involvement and contribution to iron transport.<ref name=":0">{{Citation|title=Kenneth Raymond - The Human/Bacterial Arms Race for Iron|url=https://www.youtube.com/watch?v=-uTedo32NU4|language=en|access-date=2021-12-04}}</ref> It was not until 1957 because of ]' work, where he first noted that Ferrichrome was able to act as an iron transport agent.
			== Biological function ==
⚫	==References==
			Ferrichrome is a siderophore, which are metal ]s that have a low molecular mass and are produced by microorganisms and plants growing under low iron conditions. The main function of siderophores is to chelate ferric iron (Fe<sup>3+</sup>) from insoluble minerals from the environment and make it available for microbial and plant cells. Iron is important in biological functions as it acts as a catalyst in enzymatic processes, as well as for electron transfer, DNA and RNA synthesis, and oxygen metabolism.<ref>{{cite journal | vauthors = Ahmed E, Holmström SJ | title = Siderophores in environmental research: roles and applications | journal = Microbial Biotechnology | volume = 7 | issue = 3 | pages = 196–208 | date = May 2014 | pmid = 24576157 | pmc = 3992016 | doi = 10.1111/1751-7915.12117 | doi-access = free }}</ref> Although iron is the fourth most abundant element in the ],<ref>{{Cite journal | vauthors = Loper JE, Buyer JS |date=September 1990|title=Siderophores in Microbial Interactions on Plant Surfaces|journal=Molecular Plant-Microbe Interactions|volume=4|pages=5–13|doi=10.1094/mpmi-4-005}}</ref> bioavailability of iron in aerobic environments is low due to formation of insoluble ferric hydroxides. Under iron limitation, bacteria scavenge for ferric iron (Fe<sup>3+</sup>) by up-regulating the secretion of siderophores in order to meet their nutritional requirements.<ref>{{cite journal | vauthors = Chatterjee A, O'Brian MR | title = Rapid evolution of a bacterial iron acquisition system | journal = Molecular Microbiology | volume = 108 | issue = 1 | pages = 90–100 | date = April 2018 | pmid = 29381237 | pmc = 5867251 | doi = 10.1111/mmi.13918 }}</ref> Recent studies have shown that ferrichrome has been used as a tumor- suppressive molecule produced by the bacterium '']''. The study from the Department of Medicine and Asahikawa Medical University, suggests that ferrichrome has a greater tumor-suppressive effect than other drugs currently used to fight colon cancer, including ] and ]. Ferrichrome also had less of an effect on non-cancerous intestinal cells than the two previously mentioned cancer fighting drugs. It was determined that ferrichrome activated the ], which induced ]. The induction of apoptosis by ferrichrome is reduced by the inhibition of the c-jun N-terminal kinase signaling pathway.<ref>{{cite journal | vauthors = Konishi H, Fujiya M, Tanaka H, Ueno N, Moriichi K, Sasajima J, Ikuta K, Akutsu H, Tanabe H, Kohgo Y | display-authors = 6 | title = Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis | journal = Nature Communications | volume = 7 | pages = 12365 | date = August 2016 | pmid = 27507542 | pmc = 4987524 | doi = 10.1038/ncomms12365 | doi-access = free }}</ref>
	{{reflist}}
			==Uptake==
	{{organic-compound-stub}}
			Iron is essential for the most important biological processes such as DNA and RNA synthesis, glycolysis, energy generation, nitrogen fixation and photosynthesis, therefore uptake of iron from the environment and transport into the organism are critical life processes for almost all organisms.<ref name="Hannauer">{{cite journal | vauthors = Hannauer M, Barda Y, Mislin GL, Shanzer A, Schalk IJ | title = The ferrichrome uptake pathway in Pseudomonas aeruginosa involves an iron release mechanism with acylation of the siderophore and recycling of the modified desferrichrome | journal = Journal of Bacteriology | volume = 192 | issue = 5 | pages = 1212–1220 | date = March 2010 | pmid = 20047910 | pmc = 2820845 | doi = 10.1128/JB.01539-09 }}</ref> The problem is when environmental iron is exposed to oxygen it is mineralized to its insoluble ferric oxy hydroxide form which can not be transported into the cells and therefore is not available for use by the cell.<ref name="Hannauer"/> To overcome this, bacteria, fungi and some plants synthesize siderophores, and secrete it into an extracellular environment where binding of iron can occur.<ref name="Hannauer"/> It is important to note microbes make their own type of siderophore so that they are not competing with other organisms for iron uptake.<ref name="Hannauer"/> For example, ''saccharomyces cerevisiae'' is a species of yeast that can uptake the iron bound siderophore through transporters of the ARN family.<ref name="Moore">{{cite journal | vauthors = Moore RE, Kim Y, Philpott CC | title = The mechanism of ferrichrome transport through Arn1p and its metabolism in Saccharomyces cerevisiae | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 10 | pages = 5664–5669 | date = May 2003 | pmid = 12721368 | pmc = 156258 | doi = 10.1073/pnas.1030323100 | bibcode = 2003PNAS..100.5664M | doi-access = free }}</ref> <sup>(n-3)-</sup> binds to a receptor-transporter on the cell surface and then is up taken.<ref name="Moore"/> The exact mechanism how iron enters the cell using these transporters is not understood, but it known that once it enters the cell it accumulates in the cytosol.<ref name="Moore"/> In ''saccharomyces cerevisiae'', ferrichrome is specifically taken up by ARN1P as it has 2 binding sites and ferrichrome can the higher affinity site through endocytosis.<ref name="Moore"/>  Ferrichrome chelates stay stable in the cell and allow for iron storage, but can be easily mobilized to meet the metabolic needs of the cell.<ref name="Moore"/>
⚫	]
⚫	]
⚫	]
			The removal of Fe<sup>3+</sup> occurs through the reduction of Fe<sup>3+</sup> to Fe<sup>2+</sup>.<ref>{{cite journal | vauthors = Inomata T, Eguchi H, Funahashi Y, Ozawa T, Masuda H | title = Adsorption behavior of microbes on a QCM chip modified with an artificial siderophore-Fe3+ complex | journal = Langmuir | volume = 28 | issue = 2 | pages = 1611–1617 | date = January 2012 | pmid = 22182317 | doi = 10.1021/la203250n }}</ref> The reduction strategy helps in making the iron more aqueous soluble, and allows the iron to become more ] in order for uptake to occur. This is because the Fe<sup>2+</sup> product is not able to mineralize like the Fe<sup>3+</sup>, as it does not bind significantly to the chelate ] that is designed to bind Fe<sup>3+</sup>. In addition to this, the Fe<sup>3+</sup> product can also release Fe<sup>2+</sup> from the chelate ligands that was designed to bind Fe<sup>3+</sup>. Fe<sup>2+</sup> has little to no affinity towards the siderophore ligand and this removal is necessary for use and storage. This is because Fe<sup>2+</sup> is an intermediate acid, therefore it is not able to bind significantly to the siderophore chelate ligands and can only bind with a much lower affinity. Whereas, Fe<sup>3+</sup> is a ] and can bind to the siderophore chelate ligands with a much higher affinity.<ref name=":0" /> The Fe<sup>3+</sup> ] complexes are taken up into the bacterial membrane by ] mechanisms. This uptake process is able to recognize different structural features of the siderophores and transport the Fe<sup>3+</sup> complexes into the ].
	]
			== Siderophore Binding ==
			]
			The main types of ] have catecholate, hydroxamate, and carboxylate coordinating ligands. An example of a catecholate siderophore includes ]. Examples of hydroxamate siderophores include ], ferrichrome, ], ], and alcaligin. Aerobactin is a carboxylate siderophore as well. The triscatecholate siderophore, enterobactin, has a higher binding affinity of logβ<sub>110</sub> = 49 to ferric iron compared to Ferrichrome, which has a binding affinity of logβ<sub>110</sub> = 29.07. Therefore, it would outcompete with the other siderophore and bind more of the available environmental Fe<sup>3+</sup>. It does not bind other metals in high concentration because of its high Fe<sup>3+</sup> specificity.<ref name="Moore" /> The trishydroxamate siderophore, desferrioxamine, has a binding affinity of logβ<sub>110</sub> = 30.6 and has a lower binding affinity compared to Ferrichrome. Therefore, the desferrioxamine siderophore can also outcompete Ferrichrome, and bind more of the available environmental Fe<sup>3+</sup>. However, the bishydroxamate siderophores aerobactin (logβ<sub>110</sub> = 22.5), rhodotorullic acid (logβ<sub>110</sub> =21.55), and alcaligin (logβ<sub>110</sub> = 23.5) will not be able to outcompete with the triscatecholate and trishydroxamate siderophores, since they do not have high Fe<sup>3+</sup> specificity. Therefore, they are not able to bind more of the available environmental Fe<sup>3+</sup>.
			Iron in its trivalent state has an electron configuration of d<sup>5</sup>, therefore, its complexes are preferentially hexacoordinate, quasi octahedral.<ref>{{Cite journal| vauthors = Drechsel H, Jung G |date=1998|title=Peptide siderophores|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291099-1387%28199805%294%3A3%3C147%3A%3AAID-PSC136%3E3.0.CO%3B2-C|journal=Journal of Peptide Science|language=en|volume=4|issue=3|pages=147–181|doi=10.1002/(SICI)1099-1387(199805)4:3<147::AID-PSC136>3.0.CO;2-C|pmid=9643626 |s2cid=31107931 |issn=1099-1387}}</ref> In terms of the ], ferric siderophores have donor atoms that are mainly oxygen and rarely heterocyclic nitrogen. This is because of the ferric ion being a hard ], and the ferric iron therefore binds more strongly with a hard anionic oxygen donor.
			==FhuA Uptake Mechanism==
			E. coli has a receptor protein called  FhuA (ferric Hydroxamate).<ref name="Braun">{{cite journal | vauthors = Braun V | title = FhuA (TonA), the career of a protein | journal = Journal of Bacteriology | volume = 191 | issue = 11 | pages = 3431–3436 | date = June 2009 | pmid = 19329642 | pmc = 2681897 | doi = 10.1128/JB.00106-09 }}</ref>
			FhuA’s is an energy-coupled transporter and receptor.<ref name="Braun"/> It is a part of the integral outer membrane proteins and works alongside an energy transducing protein TonB.<ref name="Ferguson">{{cite journal | vauthors = Ferguson AD, Hofmann E, Coulton JW, Diederichs K, Welte W | title = Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide | journal = Science | volume = 282 | issue = 5397 | pages = 2215–2220 | date = December 1998 | pmid = 9856937 | doi = 10.1126/science.282.5397.2215 | doi-access = free | bibcode = 1998Sci...282.2215F }}</ref> It is involved in the uptake of iron in complex with ferrichrome by binding and transporting ferrichrome-iron across the cell’s outer membrane.<ref name="Ferguson"/>
			]
			The green ribbons represent β-barrel wall that is 69Å long x 40-45Å diameter that represents the C-terminus residues. It has 22 antiparallel β strands. The blue ribbon in the center is a “cork” which is a distinct domain for the N-terminus residues.<ref name="Ferguson" />
			FhuA has L4 strand and its role is to transport ferrichrome into the β-barrel wall. The ferrichrome complex then binds tightly to both the β-barrel wall and the "cork".<ref name="Ferguson"/> As a result, these binding triggers two key conformation changes to iron-ferrichrome complex to transfer energy to the cork. This energy transfer results in subsequent conformational changes that transport iron-ferrichrome to the periplasmic pocket which signal a ligand loaded status of the receptor.<ref name="Ferguson"/> These subtle shifts disrupt the binding of iron-ferrichrome to the cork which then allows the permeation of the ferrichrome-iron to a putative channel-forming region. The inner wall of the β-barrel provides a series of weak binding sites to pull ferrichrome along.<ref name="Ferguson"/> FhuD is a high affinity binding protein in the periplasmic pocket that also aids in unidirectional transport across the cell envelope.<ref name="Ferguson"/>
			== See also ==
			]
		⚫	== References ==
			<references />
		⚫	]
		⚫	]
		⚫	]