http://www.ncbi.nlm.nih.gov/pubmed/?term=Inositol+phosphate+2-phosphatase+%2C+MIPP
Tähän asiaan törmäsin kun etsin inositolin 2- aseman fosfataasia.
LÄHDE:
Proc Natl Acad Sci U S A. 2008 Apr 22;105(16):5998-6003. doi: 10.1073/pnas.0710980105. Epub 2008 Apr 14.Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory capacity of the Rapoport-Luebering glycolytic shunt.
Abstract
The
Rapoport-Luebering glycolytic bypass comprises evolutionarily conserved
reactions that generate and dephosphorylate 2,3-bisphosphoglycerate
(2,3-BPG). For >30 years, these reactions have been considered the
responsibility of a single enzyme, the 2,3-BPG synthase/2-phosphatase
(BPGM). Here, we show that Dictyostelium, birds, and mammals contain an
additional 2,3-BPG phosphatase that, unlike BPGM, removes the 3-phosphate.
This discovery reveals that the glycolytic pathway can bypass the
formation of 3-phosphoglycerate, which is a precursor for serine
biosynthesis and an activator of AMP-activated protein kinase
. Our 2,3-BPG phosphatase activity is encoded by the previously identified gene for multiple inositol polyphosphate phosphatase (MIPP1), which we now show to have dual substrate specificity. By genetically manipulating Mipp1 expression in Dictyostelium, we demonstrated that this enzyme provides physiologically relevant regulation of cellular 2,3-BPG content.
Mammalian erythrocytes possess the highest content of 2,3-BPG, which controls oxygen binding to hemoglobin. We determined that total MIPP1 activity in erythrocytes at 37 degrees C is 0.6 mmol 2,3-BPG hydrolyzed per liter of cells per h, matching previously published estimates of the phosphatase activity of BPGM.
MIPP1 is active at 4 degrees C, revealing a clinically significant contribution to 2,3-BPG loss during the storage of erythrocytes for transfusion. Hydrolysis of 2,3-BPG by human MIPP1 is sensitive to physiologic alkalosis; activity decreases 50% when pH rises from 7.0 to 7.4. This phenomenon provides a homeostatic mechanism for elevating 2,3-BPG levels, thereby enhancing oxygen release to tissues. Our data indicate greater biological significance of the Rapoport-Luebering shunt than previously considered.
http://metacyc.org/META/new-image?type=PATHWAY&object=PWY-6405
. Our 2,3-BPG phosphatase activity is encoded by the previously identified gene for multiple inositol polyphosphate phosphatase (MIPP1), which we now show to have dual substrate specificity. By genetically manipulating Mipp1 expression in Dictyostelium, we demonstrated that this enzyme provides physiologically relevant regulation of cellular 2,3-BPG content.
Mammalian erythrocytes possess the highest content of 2,3-BPG, which controls oxygen binding to hemoglobin. We determined that total MIPP1 activity in erythrocytes at 37 degrees C is 0.6 mmol 2,3-BPG hydrolyzed per liter of cells per h, matching previously published estimates of the phosphatase activity of BPGM.
MIPP1 is active at 4 degrees C, revealing a clinically significant contribution to 2,3-BPG loss during the storage of erythrocytes for transfusion. Hydrolysis of 2,3-BPG by human MIPP1 is sensitive to physiologic alkalosis; activity decreases 50% when pH rises from 7.0 to 7.4. This phenomenon provides a homeostatic mechanism for elevating 2,3-BPG levels, thereby enhancing oxygen release to tissues. Our data indicate greater biological significance of the Rapoport-Luebering shunt than previously considered.
http://metacyc.org/META/new-image?type=PATHWAY&object=PWY-6405
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