Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:5.4.2.8 (phosphomannomutase)
 238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interconversion of glucose 1-phosphate and glucose 6-phosphate, catalyzed by Pseudomonas aeruginosa phosphomannomutase/phosphoglucomutase, has been studied by transient-state kinetic techniques. Glucose 1,6-bisphosphate is formed as an intermediate in the reaction, but an obligatory step in the catalytic cycle appears to be the formation of an enzyme-glucose 1,6-bisphosphate complex that is not competent to form either glucose 1-phosphate or glucose 6-phosphate directly. We suggest that during the lifetime of this complex the glucose 1,6-bisphosphate intermediate undergoes the 180 degrees reorientation that is required for completion of the catalytic cycle. The formation of glucose 1,6-bisphosphate from glucose 1-phosphate is in rapid equilibrium relative to the rest of the reaction, where K(eq) = 0.14. In the opposite direction, glucose 1,6-bisphosphate is formed from glucose 6-phosphate with a rate constant of 12 s(-)(1), and the reverse step occurs with a rate constant of 255 s(-)(1). The interconversion of the productive and nonproductive glucose 1,6-bisphosphate complexes occurs with a rate constant of 64 s(-)(1) in one direction and 48 s(-)(1) in the other direction. Glucose 1,6-bisphosphate remains associated with the enzyme during reorientation. Isotope trapping studies indicate that it partitions to form glucose 1-phosphate or glucose 6-phosphate 14.3 times more frequently than it dissociates from the enzyme.
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PMID:Formation and reorientation of glucose 1,6-bisphosphate in the PMM/PGM reaction: transient-state kinetic studies. 1586 28

Glucose 1,6-bisphosphate (Glc-1,6-P(2)) concentration in brain is much higher than what is required for the functioning of phosphoglucomutase, suggesting that this compound has a role other than as a cofactor of phosphomutases. In cell-free systems, Glc-1,6-P(2) is formed from 1,3-bisphosphoglycerate and Glc-6-P by two related enzymes: PGM2L1 (phosphoglucomutase 2-like 1) and, to a lesser extent, PGM2 (phosphoglucomutase 2). It is hydrolyzed by the IMP-stimulated brain Glc-1,6-bisphosphatase of still unknown identity. Our aim was to test whether Glc-1,6-bisphosphatase corresponds to the phosphomannomutase PMM1, an enzyme of mysterious physiological function sharing several properties with Glc-1,6-bisphosphatase. We show that IMP, but not other nucleotides, stimulated by >100-fold (K(a) approximately 20 mum) the intrinsic Glc-1,6-bisphosphatase activity of recombinant PMM1 while inhibiting its phosphoglucomutase activity. No such effects were observed with PMM2, an enzyme paralogous to PMM1 that physiologically acts as a phosphomannomutase in mammals. Transfection of HEK293T cells with PGM2L1, but not the related enzyme PGM2, caused an approximately 20-fold increase in the concentration of Glc-1,6-P(2). Transfection with PMM1 caused a profound decrease (>5-fold) in Glc-1,6-P(2) in cells that were or were not cotransfected with PGM2L1. Furthermore, the concentration of Glc-1,6-P(2) in wild-type mouse brain decreased with time after ischemia, whereas it did not change in PMM1-deficient mouse brain. Taken together, these data show that PMM1 corresponds to the IMP-stimulated Glc-1,6-bisphosphatase and that this enzyme is responsible for the degradation of Glc-1,6-P(2) in brain. In addition, the role of PGM2L1 as the enzyme responsible for the synthesis of the elevated concentrations of Glc-1,6-P(2) in brain is established.
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PMID:Mammalian phosphomannomutase PMM1 is the brain IMP-sensitive glucose-1,6-bisphosphatase. 1892 83