Mannose: Difference between revisions

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 413751095

| ImageFile = Mannose structure.svg

| ImageSize = 150px

| ImageCaption = <small>D</small>-Mannopyranose

| ImageFile1 = DL-Mannose.svg

| ImageFile2 = D-Mannose-chain-3D-balls.png

| ImageCaption1 = Fischer projections

| OtherNames =

| IUPACName = Mannose

| SystematicName = (3''S'',4''S'',5''S'',6''R'')-6-(hydroxymethyl)oxane-2,3,4,5-tetrol

| Section1 = {{Chembox Identifiers

| IUPHAR_ligand = 4650

| CASNo_Ref = {{cascite|changed|??}}

| CASNo = 3458-28-4

| PubChem = 18950

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 469448

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = PHA4727WTP

| KEGG = C00159

| SMILES =

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 17893

| ChemSpiderID_Comment = <small>D</small>-mannopyranose

| MeSHName = Mannose

| Section2 = {{Chembox Properties

| C=6|H=12|O=6

| Appearance =

| Density =

| MeltingPt =

| BoilingPt =

| MagSus = -102.90·10⁻⁶ cm³/mol

| Section3 = {{Chembox Hazards

| MainHazards =

| FlashPt =

| AutoignitionPt =

'''Mannose''' is a [[sugar]] [[monomer]] of the [[aldohexose]] series of [[carbohydrate]]s. It is a C-2 [[epimer]] of [[glucose]]. Mannose is important in human [[metabolism]], especially in the [[glycosylation]] of certain [[protein]]s. Several [[Congenital disorder of glycosylation|congenital disorders of glycosylation]] are associated with mutations in [[enzyme]]s involved in mannose metabolism.<ref>{{Cite journal

| last1 = Freeze | first1 = H. H.

| last2 = Sharma | first2 = V.

| doi = 10.1016/j.semcdb.2010.03.011

| title = Metabolic manipulation of glycosylation disorders in humans and animal models

| journal = Seminars in Cell & Developmental Biology

| volume = 21

| issue = 6

| pages = 655–662

| year = 2010

| pmid = 20363348

| pmc =2917643

}}</ref>

Mannose is not an [[essential nutrient]]; it can be produced in the human body from glucose, or converted into glucose. Mannose provides 2–5&nbsp;[[kcal]]/g. It is partially excreted in the [[urine]].

==Etymology==

The root of both "mannose" and "[[mannitol]]" is [[manna]], which the [[Bible]] describes as the food supplied to the Israelites during their journey in the region of [[Sinai Peninsula|Sinai]]. Several trees and shrubs can produce a substance called manna, such as the "manna tree" (''[[Fraxinus ornus]]'') from whose secretions mannitol was originally isolated.{{Citation needed|date=February 2021}}

Mannose commonly exists as two different-sized rings, the [[pyranose]] (six-membered) form and the [[furanose]] (five-membered) form. Each ring closure can have either an alpha or beta configuration at the [[anomer]]ic position. The chemical rapidly undergoes [[isomerization]] among these four forms.{{Citation needed|date=February 2021}}

{| class="wikitable"

|+ <small>D</small>-Mannose isomers ([[Haworth projection]]s)<br />Percent composition<ref name="Witczak">{{cite book |last1=Witczak |first1=Zbigniew J. |editor-first1=Bertram O. |editor-first2=Kuniaki |editor-first3=Joachim |editor-last1=Fraser-Reid |editor-last2=Tatsuta |editor-last3=Thiem |title=Glycoscience. Chemistry and Chemical Biology I–III |publisher=Springer |isbn=978-3-642-56874-9 |page=887 |doi=10.1007/978-3-642-56874-9 |chapter=Monosaccharides. Properties|date=2001 }}</ref>

|-

| align="center" | [[File:Alpha-D-Mannofuranose.svg|120px]]<br />α-<small>D</small>-Mannofuranose<br />0.6%

| align="center" | [[File:Beta-D-Mannofuranose.svg|120px]]<br />β-<small>D</small>-Mannofuranose<br />0.2%

|-

| align="center" | [[File:Alpha-D-Mannopyranose.svg|100px]]<br />α-<small>D</small>-Mannopyranose<br />63.7%

| align="center" | [[File:Beta-D-Mannopyranose.svg|100px]]<br />β-<small>D</small>-Mannopyranose<br />35.5%

[[File:Mannose metabolism.png|thumb|300x300px|Mannose metabolism in human beings ]]

While much of the mannose used in glycosylation is believed to be derived from glucose, in [[cell culture|cultured]] [[hepatoma]] cells (cancerous cells from the liver), most of the mannose for glycoprotein biosynthesis comes from extracellular mannose, not glucose.<ref>{{Cite journal

| doi = 10.1093/glycob/8.3.285

| last1 = Alton | first1 = G.

| last2 = Hasilik | first2 = M.

| last3 = Niehues | first3 = R.

| last4 = Panneerselvam | first4 = K.

| last5 = Etchison | first5 = J. R.

| last6 = Fana | first6 = F.

| last7 = Freeze | first7 = H. H.

| title = Direct utilization of mannose for mammalian glycoprotein biosynthesis

| journal = Glycobiology

| volume = 8

| issue = 3

| pages = 285–295

| year = 1998

| pmid = 9451038

| doi-access = free

}}</ref> Many of the glycoproteins produced in the liver are secreted into the bloodstream, so dietary mannose is distributed throughout the body.<ref>{{Cite journal

| doi = 10.1016/S0304-4165(01)00183-0

| last1 = Davis | first1 = J. A.

| last2 = Freeze | first2 = H. H.

| title = Studies of mannose metabolism and effects of long-term mannose ingestion in the mouse

| journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1528

| issue = 2–3

| pages = 116–126

| year = 2001

| pmid = 11687298

}}</ref>

Mannose is present in numerous glycoconjugates including [[N-linked glycosylation|''N''-linked glycosylation]] of proteins. ''C''-Mannosylation is also abundant and can be found in collagen-like regions.{{Citation needed|date=February 2021}}

The digestion of many [[polysaccharide]]s and glycoproteins yields mannose, which is phosphorylated by [[hexokinase]] to generate [[mannose-6-phosphate]]. Mannose-6-phosphate is converted to [[fructose-6-phosphate]], by the enzyme [[phosphomannose isomerase]], and then enters the [[Glycolysis|glycolytic pathway]] or is converted to [[glucose-6-phosphate]] by the [[Gluconeogenesis|gluconeogenic pathway]] of [[hepatocytes]].{{Citation needed|date=February 2021}}

Mannose is a dominant monosaccharide in ''N''-linked glycosylation, which is a [[post-translational modification]] of proteins. It is initiated by the ''en bloc'' transfer on Glc₃Man₉[[GlcNAc]]₂ to nascent glycoproteins in the [[endoplasmic reticulum]] (ER) in a co-translational manner as the protein entered through the transport system. Glucose is [[hydrolysis|hydrolyzed]] on fully folded protein and the mannose moieties are hydrolyzed by ER and [[Golgi apparatus|Golgi]]-resident [[mannosidase]]s. Typically, mature human glycoproteins only contain three mannose residues buried under sequential modification by GlcNAc, [[galactose]], and [[sialic acid]]. This is important, as the [[innate immune system]] in mammals is geared to recognise exposed mannose residues. This activity is due to the prevalence of mannose residues, in the form of mannans, on the surfaces of yeasts. The [[human immunodeficiency virus]] displays considerable amount of mannose residues due to the tight clustering of glycans in its [[viral spike]].<ref>{{Cite journal|last1=Pritchard|first1=Laura K.|last2=Spencer|first2=Daniel I. R.|last3=Royle|first3=Louise|last4=Bonomelli|first4=Camille|last5=Seabright|first5=Gemma E.|last6=Behrens|first6=Anna-Janina|last7=Kulp|first7=Daniel W.|last8=Menis|first8=Sergey|last9=Krumm|first9=Stefanie A.|date=2015-06-24|title=Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies|journal=Nature Communications|language=en|volume=6|pages=7479|doi=10.1038/ncomms8479|pmc=4500839|pmid=26105115|bibcode=2015NatCo...6.7479P}}</ref><ref>{{Cite journal|last1=Pritchard|first1=Laura K.|last2=Vasiljevic|first2=Snezana|last3=Ozorowski|first3=Gabriel|last4=Seabright|first4=Gemma E.|last5=Cupo|first5=Albert|last6=Ringe|first6=Rajesh|last7=Kim|first7=Helen J.|last8=Sanders|first8=Rogier W.|last9=Doores|first9=Katie J.|date=2015-06-16|title=Structural Constraints Determine the Glycosylation of HIV-1 Envelope Trimers|journal=Cell Reports|language=en|volume=11|issue=10|pages=1604–1613|doi=10.1016/j.celrep.2015.05.017|issn=2211-1247|pmc=4555872|pmid=26051934}}</ref> These mannose residues are the target for [[Broadly neutralizing HIV-1 antibodies|broadly neutralizing antibodies]].<ref>{{Cite journal|last1=Crispin|first1=Max|last2=Doores|first2=Katie J|author-link2=Katie Doores |date=2015-04-01|title=Targeting host-derived glycans on enveloped viruses for antibody-based vaccine design|journal=Current Opinion in Virology|series=Viral pathogenesis • Preventive and therapeutic vaccines|volume=11|pages=63–69|doi=10.1016/j.coviro.2015.02.002|pmid=25747313|pmc=4827424}}</ref>

==Biotechnology==

[[Recombinant protein]]s produced in yeast may be subject to mannose addition in patterns different from those used by mammalian cells.<ref>{{Cite journal

| last1 = Vlahopoulos | first1 = S.

| last2 = Gritzapis | first2 = A. D.

| last3 = Perez | first3 = S. A.

| last4 = Cacoullos | first4 = N.

| last5 = Papamichail | first5 = M.

| last6 = Baxevanis | first6 = C. N.

| doi = 10.1016/j.vaccine.2009.05.063

| title = Mannose addition by yeast ''Pichia pastoris'' on recombinant HER-2 protein inhibits recognition by the monoclonal antibody herceptin

| journal = Vaccine

| volume = 27

| issue = 34

| pages = 4704–4708

| year = 2009

| pmid = 19520203

}}</ref> This difference in recombinant proteins from those normally produced in mammalian organisms may influence the effectiveness of vaccines.{{Citation needed|date=February 2021}}

Mannose can be formed by the oxidation of [[mannitol]].{{Citation needed|date=February 2021}}

It can also be formed from glucose in the [[Lobry de Bruyn–Van Ekenstein transformation|Lobry de Bruyn–van Ekenstein transformation]].{{Citation needed|date=February 2021}}

==Uses==

Mannose ({{sma|D}}-mannose) is used as a [[dietary supplement]] to prevent recurrent [[urinary tract infection]]s (UTIs).<ref name="lenger">{{cite journal |last1=Lenger |first1=Stacy M. |last2=Bradley |first2=Megan S. |last3=Thomas |first3=Debbie A. |last4=Bertolet |first4=Marnie H. |last5=Lowder |first5=Jerry L. |last6=Sutcliffe |first6=Siobhan |title=D-mannose vs other agents for recurrent urinary tract infection prevention in adult women: a systematic review and meta-analysis |journal=American Journal of Obstetrics and Gynecology |date=1 August 2020 |volume=223 |issue=2 |pages=265.e1–265.e13 |doi=10.1016/j.ajog.2020.05.048 |pmid=32497610 |pmc=7395894 }}</ref><ref name="cooper">{{cite journal |last1=Cooper |first1=Tess E |last2=Teng |first2=Claris |last3=Howell |first3=Martin |last4=Teixeira-Pinto |first4=Armando |last5=Jaure |first5=Allison |last6=Wong |first6=Germaine |title=D-mannose for preventing and treating urinary tract infections |journal=Cochrane Database of Systematic Reviews |date=30 August 2022 |volume=2022 |issue=8 |pages=CD013608 |doi=10.1002/14651858.CD013608.pub2|pmid=36041061 |pmc=9427198}}</ref> {{As of|2022}}, one review found that taking mannose was as effective as [[antibiotic]]s to prevent UTIs,<ref name=lenger/> while another review found that [[clinical trial]] quality was too low to allow any conclusion about using {{sma|D}}‐mannose to prevent or treat UTIs.<ref name=cooper/> In 2024, a randomized clinical trial among 598 women with recurrent UTI recruited from primary care settings found the proportion experiencing a medically attended UTI was 51.0% in those taking daily {{sma|D}}-mannose over 6 months and 55.7% in those taking placebo, concluding that {{sma|D}}-mannose should not be recommended to prevent future episodes of medically attended UTI in women with recurrent UTI in primary care.<ref>{{cite journal|date=April 8, 2024|title=d-Mannose for Prevention of Recurrent Urinary Tract Infection Among Women {{!}} A Randomized Clinical Trial|author=Gail Hayward |author2=Sam Mort|author3=Alastair D. Hay|display-authors=3|author4=Michael Moore|author5=Nicholas P. B. Thomas|author6=Johanna Cook|author7=Jared Robinson|author8=Nicola Williams|author9=Nicola Maeder|author10=Rebecca Edeson|author11=Marloes Franssen|author12=Jenna Grabey|author13=Margaret Glogowska |author14=Yaling Yang|author15=Julie Allen|author16=Christopher C. Butler|journal=JAMA Intern. Med.|year=2024|volume=184|issue=6|pages=619–628 |doi=10.1001/jamainternmed.2024.0264 |pmid=38587819 |url=https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2817488|pmc=11002776}}</ref>

Mannose differs from glucose by inversion of the C-2 [[chiral center]]. Mannose displays a <math>^4C_1</math> pucker in the solution ring form. This simple change leads to the drastically different biochemistry of the two [[hexose]]s. This change has the same effect on the other [[aldohexose]]s, as well.{{Citation needed|date=February 2021}}

==Mannose PTS permease==

{{See also|PEP group translocation}}

[[File:MannoseComplex.jpg|thumb|250px|Mannose XYZ permease complex: entry of PEP which donates a high energy phosphate that gets passed through the transporter system and eventually assist in the entry of mannose (in this example otherwise it would any hexose sugar) and results in the formation of mannose-6-phosphate.]]

[[File:MannosePTS.ogv|thumb|left|Video illustration of the MANXYZ sugar transporter complex transferring the high energy phosphate for PEP to the other subunits of the complex]]

The PEP-dependent sugar transporting phosphotransferase system transports and simultaneously phosphorylates its sugar substrates. Mannose XYZ permease is a member of the family, with this distinct method being used by bacteria for sugar uptake particularly exogenous hexoses in the case of mannose XYZ to release the phosphate esters into the cell cytoplasm in preparation for metabolism primarily through the route of glycolysis.<ref name="Postma 1993">{{Cite journal

| last1 = Postma | first1 = P. W.

| last2 = Lengeler | first2 = J. W.

| last3 = Jacobson | first3 = G. R.

| title = Phosphoenolpyruvate:carbohydrate phosphotransferase systems of bacteria

| journal = Microbiological Reviews

| volume = 57

| issue = 3

| pages = 543–594

| year = 1993

| doi = 10.1128/MMBR.57.3.543-594.1993

| pmid = 8246840

| pmc = 372926

}}</ref> The MANXYZ transporter complex is also involved in infection of ''E. coli'' by [[bacteriophage lambda]], with subunit ManY and ManZ being sufficient for proper lambda phage infection.<ref name="Erni 1985">{{Cite journal

| last1 = Erni | first1 = B.

| last2 = Zanolari | first2 = B.

| title = The mannose-permease of the bacterial phosphotransferase system. Gene cloning and purification of the enzyme IIMan/IIIMan complex of ''Escherichia coli''

| journal = The Journal of Biological Chemistry

| volume = 260

| issue = 29

| pages = 15495–15503

| year = 1985

| doi = 10.1016/S0021-9258(17)36282-8

| pmid = 2999119

| doi-access = free

}}</ref>

MANXYZ possesses four domains in three polypeptide chains; ManX, ManY, and ManZ. The ManX subunit forms a [[homodimer]] that is localized to the cytoplasmic side of the membrane. ManX contains two domains IIA and IIB linked by a hinge peptide with each domain containing a phosphorylation site and phosphoryl transfer occurs between both subunits.<ref name="Erni 1989">{{Cite journal

| last1 = Erni | first1 = B.

| last2 = Zanolari | first2 = B.

| last3 = Graff | first3 = P.

| last4 = Kocher | first4 = H. P.

| title = Mannose permease of Escherichia coli. Domain structure and function of the phosphorylating subunit

| journal = The Journal of Biological Chemistry

| volume = 264

| issue = 31

| pages = 18733–18741

| year = 1989

| doi = 10.1016/S0021-9258(18)51529-5

| pmid = 2681202

| doi-access = free

}}</ref> ManX can be membrane bound or not.<ref name="Erni 1985"/> The ManY and ManNZ subunits are hydrophobic integral membrane proteins with six and one transmembrane alpha helical spanner(s).<ref name="Huber 1996">{{Cite journal

| doi = 10.1111/j.1432-1033.1996.0810u.x

| last1 = Huber | first1 = F.

| last2 = Erni | first2 = B.

| title = Membrane topology of the mannose transporter of ''Escherichia coli'' K12

| journal = European Journal of Biochemistry

| volume = 239

| issue = 3

| pages = 810–817

| year = 1996

| pmid = 8774730

| doi-access =

}}</ref><ref>{{Cite journal|last1=Liu|first1=Xueli|last2=Zeng|first2=Jianwei|last3=Huang|first3=Kai|last4=Wang|first4=Jiawei|date=2019-06-17|title=Structure of the mannose transporter of the bacterial phosphotransferase system|journal=Cell Research|volume=29|issue=8|pages=680–682|doi=10.1038/s41422-019-0194-z|issn=1748-7838|pmid=31209249|pmc=6796895}}</ref><ref>{{Cite journal|last1=Huang|first1=Kai|last2=Zeng|first2=Jianwei|last3=Liu|first3=Xueli|last4=Jiang|first4=Tianyu|last5=Wang|first5=Jiawei|date=2021-04-06|title=Structure of the mannose phosphotransferase system (man-PTS) complexed with microcin E492, a pore-forming bacteriocin|journal=Cell Discovery|volume=7|issue=1|pages=20|doi=10.1038/s41421-021-00253-6|issn=2056-5968|pmc=8021565|pmid=33820910}}</ref> The phosphoryl group of PEP is transferred to the imported sugar via Enzyme 1, histidine protein phosphate carrier, and then to the ManX, ManY, and ManZ subunits of the ManXYZ transportation complex, which phosphorylates the entering hexose sugar, creating a hexose-6-phosphate.{{Citation needed|date=February 2021}}

* [[alpha-Mannosidase|α-Mannosidase]]

* [[Mannose receptor]]

* [[Mannan oligosaccharide-based nutritional supplements]]

* [[Rhamnose]], 6-deoxy-<small>L</small>-mannose

* [[PTS Mannose-Fructose-Sorbose Family]]

{{clear}}

{{reflist}}

[[Category:Aldohexoses]]

[[Category:Articles containing video clips]]

[[Category:Pyranoses]]

[[Category:Glycerols]]

[[Category:Furanoses]]