Phosphoglucomutase inhibition

TAUBERGER, E., FERNIE, A.R., EMMERMANN, M., KOSSMANN, J., WILLMITZER, L., TRETHEWEY, R.N., Antisense inhibition of plastidial phosphoglucomutase provides compelling evidence that potato tuber amyloplasts import carbon from the cytosol in the form of glucose-6-phosphate, Plant J., 2000, 23, 43-53. 

G5. Ginsburg, V., and Neufeld, E. F., Inhibition of phosphoglucomutase by galactose-1-phosphate. A possible factor in galactose toxicity. Am. Chem. Soc., 132nd Meeting, New York, N.Y., 1957, p. 27C. 

Phosphoglucomutase Involved in glycogenolysis inhibition by lithium of unknown relevance... 

Inhibition of phosphoglucomutase Ribonuclease and avidin inactivation Inhibition of acetylcholine esterase... 

Many metabolic processes such as glycolysis, Krebs cycle reactions, photosynthesis, protein synthesis, and lipid metabolism are affected by exposure to F. Much of the action of F on these processes can be attributed to F-dependent inhibition of enzymes. Examples of enzymes shown to be inhibited by F include enolase, phosphoglucomutase, phosphatase, hexokinase, PEP carboxylase, pyruvate kinase, succinic dehydrogenase, malic dehydrogenase, pyrophosphatase, phytase, nitrate reductase, mitochondrial ATPase, urease (Miller et al. 1983), lipase (Yu et al. 1987), amylase (Yu et al. 1988), invertase (Yu 1996 Ouchi et al. 1999), and superoxide dismutase (SOD) (Wilde and Yu 1998). 

Since metal coordination or immobilization of the transferred phosphoryl group by multiple hydrogen bonds would inhibit the formation of a metaphosphate intermediate in an S l mechanism and would facilitate nucleophilic attack in an Sy2 mechanism, the latter process seems likely for the reactions catalyzed by staphylococcal nuclease, DNA polymerase, pyruvate kinase, fructose diphosphatase, phosphoglucomutase, (Na + K) ATPase and possibly PEP carboxylase. In creatine kinase where an S l mechanism is possible, the enzyme would have to prevent access of nucleophiles other than ADP and creatine to the reactive metaphosphate intermediate. 

Many enzymes are dependent on dissociable metal ions for their activity, and the operation of most of the important metabolic systems thus requires the presence of these cofactors. For example, the list of enzymes requiring Mg is a long one and includes the oxidases and decarboxylases for the keto acids, most of the enzymes involved in phosphate metabolism, some dehydrogenases, some peptidases, phosphoglucomutase and enolase. These enzymes may be inhibited with inhibitors forming stable complexes with Mg ions. For example, malonate and other dicarboxylic compounds are able to chelate effectively with Mg" and other metal ions, and their inhibition may result from the reduction of metal ion concentration in the medium or the removal of the metal ions from the enzyme [3] ... 

Klenow concluded that both phosphoglucomutase and phosphoiibomutase activities reside in a single protein the ratio of the two activities remained constant during purification of the enzyme from muscle, both activities were stimulated by Mg and cysteine, both exhibited the same pH optimum, and both were inhibited by inorganic anions. On the other hand, Guarino and Sable 26, 27) have purified a specific phosphoiibomutase from uterine muscle this mutase showed no requirement for divalent cations. At the present time, it is difficult to evaluate the relative physiological significance of the two mutases in the interconversion of the ribose phosphates. 

Inhibition of phosphoglucomutase by fructose-1-phosphate is another possible mechanism for the development of hypoglycemia. Another explanation for the accumulation of fructose-1-phosphate in fructosuria is that the fructoaldolase in those patients is different from that found in normal individuals. Fructose-1-phosphate and fructose-1,6-phosphate are both attacked by fructoaldolase. 

Fluoride ions also inhibit a number of other magnesium-dependent enzymes including phosphoglucomutase, kinases and most phosphatases. Inhibition is rapid but reversible if the ion is removed and it is thought to result from the formation of an insoluble magnesium-phosphate-fluoride complex. 

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