Heptose

A heptose is a monosaccharide with seven carbon atoms.

They have either an aldehyde functional group in position 1 (aldoheptoses) or a ketone functional group in position 2, 3 or 4 (ketoheptoses). Ketoheptoses have 4 chiral centers, whereas aldoheptoses have 5.

Examples

There are few examples of seven-carbon sugars in nature, among which are:

sedoheptulose or D-altro-heptulose (a ketose), an intermediate in the Calvin cycle and in lipid A biosynthesis^[1]^[2]
mannoheptulose (a ketose), found in avocadoes^[3]
L-glycero-D-manno-heptose (an aldose), a late intermediate in lipid A biosynthesis.^[4]

Structural role

The production of heptose is conserved across gram-negative bacteria. In the form of L-glycero-D-mannose-heptose, heptose is a key component in the secondary membrane of gram-negative bacteria. Gram-negative bacteria, in addition to having a cell wall, are also encapsulated by a membrane composed of lipopolysaccharides.^[5] These lipopolysaccharides comprise an endotoxin that acts as an immune system agonist and elicits strong responses. This toxin, known as lipid A, consists of a core of one to three heptose molecules.^[5] The 7-carbon heptose molecules are essential for stability in the lipopolysaccharide membrane, forming an interconnected network utilizing divalent cations.^[5]

Role in cell signaling

Heptose, in the form of heptose 1-7-bisphosphate, has been found to be one of the components responsible for the pathogenic nature of gram negative bacteria. In the bacterium biosynthesis pathway, heptose is phosphorylated to heptose 1-7-bisphosphate. In addition, like other sugars, heptose may exist in either the alpha anomer or the beta anomer. Before synthetic production of heptose-bisphosphate (HBP) for studies, cytosolic HBP was thought to influence NF-kB, a transcription factor in mammalian cells.^[5]^[6] Along with producing the first synthetic version of HBP, it was shown that the beta form of the heptose acts as a pathogen-associated molecular pattern (PAMP) and activates the NF-kB signaling pathway.^[6] A PAMP is a specific structure, component, or molecule that triggers the immune response after recognition by pattern recognition receptors on mammalian cells.^[5]

References

^ Horecker, B. L; Smyrniotis, P. Z (1953). "Transaldolase: The Formation of Fructose-6-Phosphate from Sedoheptulose-7-Phosphate". Journal of the American Chemical Society. 75 (8): 2021. Bibcode:1953JAChS..75.2021H. doi:10.1021/ja01104a532.
^ Patra, Krushna C; Hay, Nissim (2014). "The pentose phosphate pathway and cancer". Trends in Biochemical Sciences. 39 (8): 347–354. doi:10.1016/j.tibs.2014.06.005. PMC 4329227. PMID 25037503.
^ Liu, Xuan; Sievert, James; Arpaia, Mary Lu; Madore, Monica A. (2002-01-01). "Postulated Physiological Roles of the Seven-carbon Sugars, Mannoheptulose, and Perseitol in Avocado". Journal of the American Society for Horticultural Science. 127 (1): 108–114. doi:10.21273/JASHS.127.1.108. Retrieved 2018-06-26.
^ Taylor, Patricia L.; Blakely, Kim M.; de Leon, Gladys P.; Walker, John R.; McArthur, Fiona; Evdokimova, Elena; Zhang, Kun; Valvano, Miguel A.; Wright, Gerard D.; Junop, Murray S. (1 February 2008). "Structure and Function of Sedoheptulose-7-phosphate Isomerase, a Critical Enzyme for Lipopolysaccharide Biosynthesis and a Target for Antibiotic Adjuvants". Journal of Biological Chemistry. 283 (5): 2835–2845. doi:10.1074/jbc.M706163200. PMID 18056714.
^ ^a ^b ^c ^d ^e Gaudet, Ryan G.; Gray-Owen, Scott D. (2016-09-22). "Heptose Sounds the Alarm: Innate Sensing of a Bacterial Sugar Stimulates Immunity". PLOS Pathogens. 12 (9): e1005807. doi:10.1371/journal.ppat.1005807. ISSN 1553-7374. PMC 5033458. PMID 27658039.
^ ^a ^b Inuki, Shinsuke; Aiba, Toshihiko; Kawakami, Shota; Akiyama, Taishin; Inoue, Jun-ichiro; Fujimoto, Yukari (2017-06-16). "Chemical Synthesis of d - glycero - d - manno -Heptose 1,7-Bisphosphate and Evaluation of Its Ability to Modulate NF-κB Activation". Organic Letters. 19 (12): 3079–3082. doi:10.1021/acs.orglett.7b01158. ISSN 1523-7060. PMID 28541700.

[1] Horecker, B. L; Smyrniotis, P. Z (1953). "Transaldolase: The Formation of Fructose-6-Phosphate from Sedoheptulose-7-Phosphate". Journal of the American Chemical Society. 75 (8): 2021. Bibcode:1953JAChS..75.2021H. doi:10.1021/ja01104a532.

[2] Patra, Krushna C; Hay, Nissim (2014). "The pentose phosphate pathway and cancer". Trends in Biochemical Sciences. 39 (8): 347–354. doi:10.1016/j.tibs.2014.06.005. PMC 4329227. PMID 25037503.

[AvocadoHeptoses-3] Liu, Xuan; Sievert, James; Arpaia, Mary Lu; Madore, Monica A. (2002-01-01). "Postulated Physiological Roles of the Seven-carbon Sugars, Mannoheptulose, and Perseitol in Avocado". Journal of the American Society for Horticultural Science. 127 (1): 108–114. doi:10.21273/JASHS.127.1.108. Retrieved 2018-06-26.

[4] Taylor, Patricia L.; Blakely, Kim M.; de Leon, Gladys P.; Walker, John R.; McArthur, Fiona; Evdokimova, Elena; Zhang, Kun; Valvano, Miguel A.; Wright, Gerard D.; Junop, Murray S. (1 February 2008). "Structure and Function of Sedoheptulose-7-phosphate Isomerase, a Critical Enzyme for Lipopolysaccharide Biosynthesis and a Target for Antibiotic Adjuvants". Journal of Biological Chemistry. 283 (5): 2835–2845. doi:10.1074/jbc.M706163200. PMID 18056714.

[:0-5] Gaudet, Ryan G.; Gray-Owen, Scott D. (2016-09-22). "Heptose Sounds the Alarm: Innate Sensing of a Bacterial Sugar Stimulates Immunity". PLOS Pathogens. 12 (9): e1005807. doi:10.1371/journal.ppat.1005807. ISSN 1553-7374. PMC 5033458. PMID 27658039.

[:1-6] Inuki, Shinsuke; Aiba, Toshihiko; Kawakami, Shota; Akiyama, Taishin; Inoue, Jun-ichiro; Fujimoto, Yukari (2017-06-16). "Chemical Synthesis of d - glycero - d - manno -Heptose 1,7-Bisphosphate and Evaluation of Its Ability to Modulate NF-κB Activation". Organic Letters. 19 (12): 3079–3082. doi:10.1021/acs.orglett.7b01158. ISSN 1523-7060. PMID 28541700.

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