Mannose 6-phosphate
Fixed
Template: Infobox chemical / molecular formula search available
D-mannose -6-phosphate, M6P abbreviation is a phosphoric ester of the mannose. M6P is a major metabolite of many metabolic processes in all living things.
Physiological significance
Free mannose is phosphorylated by hexokinase within a cell to M6P, which they can not leave the cell. If no cell from the M6P needed for the construction of glycoproteins, it may be converted into fructose -6-phosphate under the catalytic influence of the enzyme mannose-6 -phosphate isomerase, which can be recycled by means of glycolysis.
Mannose -6-phosphate serves as a recognition molecule for lysosomal enzymes. The hydrolases produced in the rough endoplasmic reticulum carry oligosaccharides with several nitrogen-bonded mannose residues. These mannose residues are phosphorylated in the cis -Golgi network. The thus formed M6P residue for the further transport of these enzymes is of great importance. Via signal areas in the peptide sequence in the cell is ensured that only the mannose groups of the lysosomal enzymes, and other enzymes not be phosphorylated. The phosphorylation takes place in two enzyme-catalyzed steps. The phosphotransferase N- acetylglucosaminyl -1 - phosphotransferase ( EC 2.7.8.17, GlcNAc phosphotransferase ) adds a first N-acetylglucosamine -1-phosphate moiety on an asparagine. A second enzyme, N- acetylglucosamine -1 - phosphodiester α -N- acetylglucosaminidase, then cuts off the N-acetylglucosamine residue. The number of M6P units correlated with the strength of the detection signal. Membrane-bound mannose 6 -phosphate receptors in the trans -Golgi network bind to the M6P units of the enzymes and provide for the formation of clathrin- coated vesicles ( clathrin coated vesicles ) that the complex formed by enzyme - M6P and M6P receptor include. The vesicles then fuse with endolysosomes and lose their Clathrinhülle. By the low pH in the lysosome of the complex will be destroyed and removed the phosphate group of the mannose. The released M6P receptors are again transported via vesicles back into the trans - Golgi network, where they are available again for the enzyme transport.
Further Reading
- Tiede S. Synthesis of mannose 6- phosphate recognition marker lysosomal enzymes: molecular analysis of the human UDP-N- acetylglucosamine: lysosomal enzyme N-acetylglucosamine -1 - phosphotransferase. Dissertation, University of Hamburg, 2005