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Pathway Description
Fructose and Mannose Metabolism
Drosophila melanogaster
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2020-06-21
Last Updated: 2023-10-28
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
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