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Pathway Description
Fructose and Mannose Metabolism
Drosophila melanogaster
Metabolic Pathway
Fructose and mannose are monosaccharides that can be found in a variety of foods, though they are both metabolized and treated differently by the body. For mannose, it begins with the D-form D-mannose which is widely distributed in mannans and hemicelluloses. D-Mannose (which can be found in the mitochondria or outside cells) is first taken up into the intracellular space by a phosphotransferase system (hexokinase) and converted into mannose-6-phosphate. This can then take one of two pathways. In the first it is subsequently converted by mannose-6-phosphate isomerase into β-D-fructose 6-phosphate, an intermediate of glycolysis. The β-D-fructose 6-phosphate is further phosphorylated by fructose-1,6-bisphosphatase to β-D-fructose 1,6-bisphosphate, which can also be converted back via ATP dependent 6-phosphofructokinase. The β-D-fructose 1,6-bisphosphate is then split into two compounds: dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate, which either continues through glycolysis, or gets catalyzed by triosephosphate isomerase into dihydroxyacetone phosphate in a reversible reaction. The second pathway for mannose-6-phosphate begins with its conversion into D-mannose 1-phosphate by phosphomannomutase 1. D-Mannose 1-phosphate is then converted into diphosphoric acid and guanosine diphosphate mannose (GDP mannose), which is a substrate for dolichol-linked oligosaccharide synthesis. GDP mannose can either continue on into N-glycan biosynthesis, or be converted to GDP-L-fucose via 3 enzymatic reactions carried out by two proteins: GDP-mannose 4,6-dehydratase (which produces the intermediate GDP-4-dehydro-6-deoxy-D-mannose) and GDP-L-fucose synthase, which converts the intermediate into GDP-L-fucose. The metabolism of mannose is interlinked with the metabolism of fructose, which begins with D-fructose also within the mitochondria. Metabolism of fructose is linked up with metabolism of mannose via fructolysis wherein ketohexokinase initially produces D-fructose 1-phosphate, (found in the cytosol). This is then split by fructose bisphosphate aldolase into D-glyceraldehyde and dihydroxyacetone phosphate, linking it to the mannose metabolic pathway. Alternatively, D-fructose can also be converted into β-D-fructose 6-phosphate by hexokinase as it is imported into the cytosol of the cell. β-D-Fructose 6-phosphate then enters the previously outlined pathway shared between fructose and mannose. D-Fructose can also be reversibly converted to sorbitol by a sorbitol dehydrogenase (LD47736p), which is subsequently reversibly converted to α-D-glucose used in the galactose metabolic pathway via an aldose reductase (CG6084, isoform D). Alternatively, D-fructose could also instead go on to take part in the amino sugar and nucleotide sugar metabolic pathway.
References
Fructose and Mannose Metabolism References
Malek, A.A., Hy, M., Honegger, A., Rose, K., Brenner-Holzach, O., 1988. Fructose-1,6-bisphosphate aldolase from Drosophila melanogaster: Primary structure analysis, secondary structure prediction, and comparison with vertebrate aldolases. Archives of Biochemistry and Biophysics.. doi:10.1016/0003-9861(88)90232-9
National Center for Biotechnology Information. PubChem Database. Guanosine diphosphate mannose, CID=135398627, https://pubchem.ncbi.nlm.nih.gov/compound/GDP-mannose (accessed on July 6, 2020)
Korner C, Lehle L, von Figura K: Abnormal synthesis of mannose 1-phosphate derived carbohydrates in carbohydrate-deficient glycoprotein syndrome type I fibroblasts with phosphomannomutase deficiency. Glycobiology. 1998 Feb;8(2):165-71. doi: 10.1093/glycob/8.2.165.
Pubmed: 9451026
Van Schaftingen E, Jaeken J: Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I. FEBS Lett. 1995 Dec 27;377(3):318-20. doi: 10.1016/0014-5793(95)01357-1.
Pubmed: 8549746
Orvisky E, Stubblefield B, Long RT, Martin BM, Sidransky E, Krasnewich D: Phosphomannomutase activity in congenital disorders of glycosylation type Ia determined by direct analysis of the interconversion of mannose-1-phosphate to mannose-6-phosphate by high-pH anion-exchange chromatography with pulsed amperometric detection. Anal Biochem. 2003 Jun 1;317(1):12-8. doi: 10.1016/s0003-2697(03)00109-x.
Pubmed: 12729595
National Center for Biotechnology Information. PubChem Database. D-Mannose 1-phosphate, CID=644175, https://pubchem.ncbi.nlm.nih.gov/compound/D-Mannose-1-phosphate (accessed on July 6, 2020)
Berg, Jeremy M.; Tymoczko, Stryer (2002). Biochemistry (5th ed.). New York: W.H. Freeman and Company. ISBN 0-7167-3051-0
Berg, Jeremy M.; Tymoczko, Stryer (2002). Biochemistry (5th ed.). New York: W.H. Freeman and Company. ISBN 0-7167-3051-0
Wu H, Zhang W, Mu W: Recent studies on the biological production of D-mannose. Appl Microbiol Biotechnol. 2019 Nov;103(21-22):8753-8761. doi: 10.1007/s00253-019-10151-3. Epub 2019 Oct 22.
Pubmed: 31637494
Elferink H, Geurts K, Jue S, MacCormick S, Veeneman G, Boltje TJ: Synthesis and cellular uptake of carbamoylated mannose derivatives. Carbohydr Res. 2019 Jul 15;481:67-71. doi: 10.1016/j.carres.2019.06.008. Epub 2019 Jun 15.
Pubmed: 31252337
Sharma V, Ichikawa M, Freeze HH: Mannose metabolism: more than meets the eye. Biochem Biophys Res Commun. 2014 Oct 17;453(2):220-8. doi: 10.1016/j.bbrc.2014.06.021. Epub 2014 Jun 12.
Pubmed: 24931670
McGrane, MM (2006). Carbohydrate Metabolism: synthesis and Oxidation. Missouri: Saunders, Elsevier. pp. 258–277
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