Mannose

Last updated
Mannose
Mannose structure.svg
D-Mannopyranose
DL-Mannose.svg
Fischer projections
D-Mannose-chain-3D-balls.png
Names
IUPAC name
Mannose
Systematic IUPAC name
(3S,4S,5S,6R)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol
Identifiers
ChEMBL
ChemSpider
  • 17893 D-mannopyranose X mark.svgN
KEGG
MeSH Mannose
PubChem CID
UNII
Properties
C6H12O6
Molar mass 180.156 g·mol−1
Appearancewhite solid
Density 1.554 g/cm3
Melting point 132 °C (270 °F; 405 K)
-102.90·10−6 cm3/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Mannose is a sugar with the formula HOCH2(CHOH)4CHO. It is one of the monomers of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation are associated with mutations in enzymes involved in mannose metabolism. [1]

Contents

Mannose is not an essential nutrient; it can be produced in the human body from glucose, or converted into glucose. Mannose provides 2–5  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. 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 ]

Structure

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 anomeric position. The chemical rapidly undergoes isomerization among these four forms.[ citation needed ]

D-Mannose isomers (Haworth projections)
Percent composition [2]
Alpha-D-Mannofuranose.svg
α-D-Mannofuranose
0.6%		 Beta-D-Mannofuranose.svg
β-D-Mannofuranose
0.2%
Alpha-D-Mannopyranose.svg
α-D-Mannopyranose
63.7%		 Beta-D-Mannopyranose.svg
β-D-Mannopyranose
35.5%

Metabolism

Mannose metabolism in human beings Mannose metabolism.png
Mannose metabolism in human beings

While much of the mannose used in glycosylation is believed to be derived from glucose, in cultured hepatoma cells (cancerous cells from the liver), most of the mannose for glycoprotein biosynthesis comes from extracellular mannose, not glucose. [3] Many of the glycoproteins produced in the liver are secreted into the bloodstream, so dietary mannose is distributed throughout the body. [4]

Mannose is present in numerous glycoconjugates including N-linked glycosylation of proteins. C-Mannosylation is also abundant and can be found in collagen-like regions.[ citation needed ]

The digestion of many polysaccharides 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 glycolytic pathway or is converted to glucose-6-phosphate by the gluconeogenic pathway of hepatocytes.[ citation needed ]

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 hydrolyzed on fully folded protein and the mannose moieties are hydrolyzed by ER and Golgi-resident mannosidases. 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. [5] [6] These mannose residues are the target for broadly neutralizing antibodies. [7]

Biotechnology

Recombinant proteins produced in yeast may be subject to mannose addition in patterns different from those used by mammalian cells. [8] This difference in recombinant proteins from those normally produced in mammalian organisms may influence the effectiveness of vaccines.[ citation needed ]

Formation

Mannose can be formed by the oxidation of mannitol.[ citation needed ]

It can also be formed from glucose in the Lobry de Bruyn–van Ekenstein transformation.[ citation needed ]

Uses

Mannose (D-mannose) is used as a dietary supplement to prevent recurrent urinary tract infections (UTIs). [9] [10] As of 2022, one review found that taking mannose was as effective as antibiotics to prevent UTIs, [9] while another review found that clinical trial quality was too low to allow any conclusion about using D‐mannose to prevent or treat UTIs. [10] 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 D-mannose over 6 months and 55.7% in those taking placebo, concluding that D-mannose should not be recommended to prevent future episodes of medically attended UTI in women with recurrent UTI in primary care. [11]

Configuration

Mannose differs from glucose by inversion of the C-2 chiral center. Mannose displays a pucker in the solution ring form. This simple change leads to the drastically different biochemistry of the two hexoses. This change has the same effect on the other aldohexoses, as well.[ citation needed ]

Mannose PTS permease

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. MannoseComplex.jpg
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.
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. [12] 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. [13] 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. [14] ManX can be membrane bound or not. [13] The ManY and ManNZ subunits are hydrophobic integral membrane proteins with six and one transmembrane alpha helical spanner(s). [15] [16] [17] 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 ]

See also

Related Research Articles

<span class="mw-page-title-main">Phosphorylation</span> Chemical process of introducing a phosphate

In biochemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology. Protein phosphorylation often activates many enzymes.

<span class="mw-page-title-main">Hexokinase</span> Class of enzymes

A hexokinase is an enzyme that irreversibly phosphorylates hexoses, forming hexose phosphate. In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important product. Hexokinase possesses the ability to transfer an inorganic phosphate group from ATP to a substrate.

<span class="mw-page-title-main">Glycoprotein</span> Protein with oligosaccharide modifications

Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated.

A congenital disorder of glycosylation is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defective. Congenital disorders of glycosylation are sometimes known as CDG syndromes. They often cause serious, sometimes fatal, malfunction of several different organ systems in affected infants. The most common sub-type is PMM2-CDG where the genetic defect leads to the loss of phosphomannomutase 2 (PMM2), the enzyme responsible for the conversion of mannose-6-phosphate into mannose-1-phosphate.

Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule in order to form a glycoconjugate. In biology, glycosylation usually refers to an enzyme-catalysed reaction, whereas glycation may refer to a non-enzymatic reaction.

PEP group translocation, also known as the phosphotransferase system or PTS, is a distinct method used by bacteria for sugar uptake where the source of energy is from phosphoenolpyruvate (PEP). It is known to be a multicomponent system that always involves enzymes of the plasma membrane and those in the cytoplasm.

The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate portion of a glycoconjugate, such as a glycoprotein, glycolipid, or a proteoglycan, even if the carbohydrate is only an oligosaccharide. Glycans usually consist solely of O-glycosidic linkages of monosaccharides. For example, cellulose is a glycan composed of β-1,4-linked D-glucose, and chitin is a glycan composed of β-1,4-linked N-acetyl-D-glucosamine. Glycans can be homo- or heteropolymers of monosaccharide residues, and can be linear or branched.

<span class="mw-page-title-main">Oligosaccharyltransferase</span> Class of enzymes

Oligosaccharyltransferase or OST (EC 2.4.1.119) is a membrane protein complex that transfers a 14-sugar oligosaccharide from dolichol to nascent protein. It is a type of glycosyltransferase. The sugar Glc3Man9GlcNAc2 (where Glc=Glucose, Man=Mannose, and GlcNAc=N-acetylglucosamine) is attached to an asparagine (Asn) residue in the sequence Asn-X-Ser or Asn-X-Thr where X is any amino acid except proline. This sequence is called a glycosylation sequon. The reaction catalyzed by OST is the central step in the N-linked glycosylation pathway.

<span class="mw-page-title-main">Lectin pathway</span> Type of cascade reaction in the compliment system

The lectin pathway or MBL pathway is a type of cascade reaction in the complement system, similar in structure to the classical complement pathway, in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade. In contrast to the classical complement pathway, the lectin pathway does not recognize an antibody bound to its target. The lectin pathway starts with mannose-binding lectin (MBL) or ficolin binding to certain sugars.

Inclusion-cell (I-cell) disease, also referred to as mucolipidosis II, is part of the lysosomal storage disease family and results from a defective phosphotransferase. This enzyme transfers phosphate to mannose residues on specific proteins. Mannose-6-phosphate serves as a marker for proteins to be targeted to lysosomes within the cell. Without this marker, proteins are instead secreted outside the cell, which is the default pathway for proteins moving through the Golgi apparatus. Lysosomes cannot function without these proteins, which function as catabolic enzymes for the normal breakdown of substances in various tissues throughout the body. As a result, a buildup of these substances occurs within lysosomes because they cannot be degraded, resulting in the characteristic I-cells, or "inclusion cells" seen microscopically. In addition, the defective lysosomal enzymes normally found only within lysosomes are instead found in high concentrations in the blood, but they remain inactive at blood pH because they require the low lysosomal pH 5 to function.

<span class="mw-page-title-main">UTP—glucose-1-phosphate uridylyltransferase</span> Class of enzymes

UTP—glucose-1-phosphate uridylyltransferase also known as glucose-1-phosphate uridylyltransferase is an enzyme involved in carbohydrate metabolism. It synthesizes UDP-glucose from glucose-1-phosphate and UTP; i.e.,

<span class="mw-page-title-main">UDP-glucose 4-epimerase</span> Class of enzymes

The enzyme UDP-glucose 4-epimerase, also known as UDP-galactose 4-epimerase or GALE, is a homodimeric epimerase found in bacterial, fungal, plant, and mammalian cells. This enzyme performs the final step in the Leloir pathway of galactose metabolism, catalyzing the reversible conversion of UDP-galactose to UDP-glucose. GALE tightly binds nicotinamide adenine dinucleotide (NAD+), a co-factor required for catalytic activity.

In enzymology, a protein-Npi-phosphohistidine-sugar phosphotransferase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">PMM1</span> Protein-coding gene in the species Homo sapiens

Phosphomannomutase 1 is an enzyme that in humans is encoded by the PMM1 gene.

<span class="mw-page-title-main">DPM1</span> Protein-coding gene in the species Homo sapiens

Dolichol-phosphate mannosyltransferase is an enzyme that in humans is encoded by the DPM1 gene.

<i>N</i>-linked glycosylation Attachment of an oligosaccharide to a nitrogen atom

N-linked glycosylation is the attachment of an oligosaccharide, a carbohydrate consisting of several sugar molecules, sometimes also referred to as glycan, to a nitrogen atom, in a process called N-glycosylation, studied in biochemistry. The resulting protein is called an N-linked glycan, or simply an N-glycan.

O-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine (Ser) or threonine (Thr) residues in a protein. O-glycosylation is a post-translational modification that occurs after the protein has been synthesised. In eukaryotes, it occurs in the endoplasmic reticulum, Golgi apparatus and occasionally in the cytoplasm; in prokaryotes, it occurs in the cytoplasm. Several different sugars can be added to the serine or threonine, and they affect the protein in different ways by changing protein stability and regulating protein activity. O-glycans, which are the sugars added to the serine or threonine, have numerous functions throughout the body, including trafficking of cells in the immune system, allowing recognition of foreign material, controlling cell metabolism and providing cartilage and tendon flexibility. Because of the many functions they have, changes in O-glycosylation are important in many diseases including cancer, diabetes and Alzheimer's. O-glycosylation occurs in all domains of life, including eukaryotes, archaea and a number of pathogenic bacteria including Burkholderia cenocepacia, Neisseria gonorrhoeae and Acinetobacter baumannii.

Permease of phosphotransferase system is a superfamily of phosphotransferase enzymes that facilitate the transport of L-ascorbate (A) and galactitol (G). Classification has been established through phylogenic analysis and bioinformatics.

The PTS Mannose-Fructose-Sorbose (Man) Family is a group of multicomponent PTS systems that are involved in sugar uptake in bacteria. This transport process is dependent on several cytoplasmic phosphoryl transfer proteins - Enzyme I (I), HPr, Enzyme IIA (IIA), and Enzyme IIB (IIB) as well as the integral membrane sugar permease complex (IICD). It is not part of the PTS-AG or PTS-GFL superfamilies.

N-glycosyltransferase is an enzyme in prokaryotes which transfers individual hexoses onto asparagine sidechains in substrate proteins, using a nucleotide-bound intermediary, within the cytoplasm. They are distinct from regular N-glycosylating enzymes, which are oligosaccharyltransferases that transfer pre-assembled oligosaccharides. Both enzyme families however target a shared amino acid sequence asparagine—-any amino acid except proline—serine or threonine (N–x–S/T), with some variations.

References

  1. ↑ Freeze, H. H.; Sharma, V. (2010). "Metabolic manipulation of glycosylation disorders in humans and animal models". Seminars in Cell & Developmental Biology. 21 (6): 655–662. doi:10.1016/j.semcdb.2010.03.011. PMC   2917643 . PMID   20363348.
  2. ↑ Witczak, Zbigniew J. (2001). "Monosaccharides. Properties". In Fraser-Reid, Bertram O.; Tatsuta, Kuniaki; Thiem, Joachim (eds.). Glycoscience. Chemistry and Chemical Biology I–III. Springer. p. 887. doi:10.1007/978-3-642-56874-9. ISBN   978-3-642-56874-9.
  3. ↑ Alton, G.; Hasilik, M.; Niehues, R.; Panneerselvam, K.; Etchison, J. R.; Fana, F.; Freeze, H. H. (1998). "Direct utilization of mannose for mammalian glycoprotein biosynthesis". Glycobiology. 8 (3): 285–295. doi: 10.1093/glycob/8.3.285 . PMID   9451038.
  4. ↑ Davis, J. A.; Freeze, H. H. (2001). "Studies of mannose metabolism and effects of long-term mannose ingestion in the mouse". Biochimica et Biophysica Acta (BBA) - General Subjects. 1528 (2–3): 116–126. doi:10.1016/S0304-4165(01)00183-0. PMID   11687298.
  5. ↑ Pritchard, Laura K.; Spencer, Daniel I. R.; Royle, Louise; Bonomelli, Camille; Seabright, Gemma E.; Behrens, Anna-Janina; Kulp, Daniel W.; Menis, Sergey; Krumm, Stefanie A. (2015-06-24). "Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies". Nature Communications. 6: 7479. Bibcode:2015NatCo...6.7479P. doi:10.1038/ncomms8479. PMC   4500839 . PMID   26105115.
  6. ↑ Pritchard, Laura K.; Vasiljevic, Snezana; Ozorowski, Gabriel; Seabright, Gemma E.; Cupo, Albert; Ringe, Rajesh; Kim, Helen J.; Sanders, Rogier W.; Doores, Katie J. (2015-06-16). "Structural Constraints Determine the Glycosylation of HIV-1 Envelope Trimers". Cell Reports. 11 (10): 1604–1613. doi:10.1016/j.celrep.2015.05.017. ISSN   2211-1247. PMC   4555872 . PMID   26051934.
  7. ↑ Crispin, Max; Doores, Katie J (2015-04-01). "Targeting host-derived glycans on enveloped viruses for antibody-based vaccine design". Current Opinion in Virology. Viral pathogenesis • Preventive and therapeutic vaccines. 11: 63–69. doi:10.1016/j.coviro.2015.02.002. PMC   4827424 . PMID   25747313.
  8. ↑ Vlahopoulos, S.; Gritzapis, A. D.; Perez, S. A.; Cacoullos, N.; Papamichail, M.; Baxevanis, C. N. (2009). "Mannose addition by yeast Pichia pastoris on recombinant HER-2 protein inhibits recognition by the monoclonal antibody herceptin". Vaccine. 27 (34): 4704–4708. doi:10.1016/j.vaccine.2009.05.063. PMID   19520203.
  9. 1 2 Lenger, Stacy M.; Bradley, Megan S.; Thomas, Debbie A.; Bertolet, Marnie H.; Lowder, Jerry L.; Sutcliffe, Siobhan (1 August 2020). "D-mannose vs other agents for recurrent urinary tract infection prevention in adult women: a systematic review and meta-analysis". American Journal of Obstetrics and Gynecology. 223 (2): 265.e1–265.e13. doi:10.1016/j.ajog.2020.05.048. PMC   7395894 . PMID   32497610.
  10. 1 2 Cooper, Tess E; Teng, Claris; Howell, Martin; Teixeira-Pinto, Armando; Jaure, Allison; Wong, Germaine (30 August 2022). "D-mannose for preventing and treating urinary tract infections". Cochrane Database of Systematic Reviews. 2022 (8): CD013608. doi:10.1002/14651858.CD013608.pub2. PMC   9427198 . PMID   36041061.
  11. ↑ Gail Hayward; Sam Mort; Alastair D. Hay; et al. (April 8, 2024). "d-Mannose for Prevention of Recurrent Urinary Tract Infection Among Women | A Randomized Clinical Trial". JAMA Intern. Med. 184 (6): 619–628. doi:10.1001/jamainternmed.2024.0264. PMC   11002776 . PMID   38587819.{{cite journal}}: CS1 maint: date and year (link)
  12. ↑ Postma, P. W.; Lengeler, J. W.; Jacobson, G. R. (1993). "Phosphoenolpyruvate:carbohydrate phosphotransferase systems of bacteria". Microbiological Reviews. 57 (3): 543–594. doi:10.1128/MMBR.57.3.543-594.1993. PMC   372926 . PMID   8246840.
  13. 1 2 Erni, B.; Zanolari, B. (1985). "The mannose-permease of the bacterial phosphotransferase system. Gene cloning and purification of the enzyme IIMan/IIIMan complex of Escherichia coli". The Journal of Biological Chemistry. 260 (29): 15495–15503. doi: 10.1016/S0021-9258(17)36282-8 . PMID   2999119.
  14. ↑ Erni, B.; Zanolari, B.; Graff, P.; Kocher, H. P. (1989). "Mannose permease of Escherichia coli. Domain structure and function of the phosphorylating subunit". The Journal of Biological Chemistry. 264 (31): 18733–18741. doi: 10.1016/S0021-9258(18)51529-5 . PMID   2681202.
  15. ↑ Huber, F.; Erni, B. (1996). "Membrane topology of the mannose transporter of Escherichia coli K12". European Journal of Biochemistry. 239 (3): 810–817. doi:10.1111/j.1432-1033.1996.0810u.x. PMID   8774730.
  16. ↑ Liu, Xueli; Zeng, Jianwei; Huang, Kai; Wang, Jiawei (2019-06-17). "Structure of the mannose transporter of the bacterial phosphotransferase system". Cell Research. 29 (8): 680–682. doi:10.1038/s41422-019-0194-z. ISSN   1748-7838. PMC   6796895 . PMID   31209249.
  17. ↑ Huang, Kai; Zeng, Jianwei; Liu, Xueli; Jiang, Tianyu; Wang, Jiawei (2021-04-06). "Structure of the mannose phosphotransferase system (man-PTS) complexed with microcin E492, a pore-forming bacteriocin". Cell Discovery. 7 (1): 20. doi:10.1038/s41421-021-00253-6. ISSN   2056-5968. PMC   8021565 . PMID   33820910.
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