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)

Carbohydrate deficient glycoprotein syndromes (CDGS) are inherited disorders in glycosylation. Isoelectric focusing of serum transferrin is used as a biochemical indicator of CDGS; however, this technique cannot diagnose the molecular defect. Even though phosphomannomutase (PMM) deficiency accounts for the great majority of known CDGS cases (CDGS type Ia), newly discovered cases have significantly different clinical presentations than the PMM-deficient patients. These differences arise from other defects affecting the biosynthesis of N-linked oligosaccharides in the endoplasmic reticulum and in the Golgi compartment. The most notable is the loss of phosphomannose isomerase (PMI) (CDGS type Ib). It causes severe hypoglycemia, protein-losing enteropathy, vomiting, diarrhea, and congenital hepatic fibrosis. In contrast to PMM-deficiency, there is no developmental delay nor neuropathy. Most symptoms in the PMI-deficient patients can be successfully treated with dietary mannose supplements. Another defect is the lack of glucosylation of the lipid-linked oligosaccharide precursor. The clinical features of this form of CDGS are milder, but similar to, PMM-deficient patients. Yeast genetic and biochemical techniques were critical in unraveling these disorders since many of the defective genes were known in yeast and corresponding mutants were available for complementation. Yeast strains carrying mutations in the homologous genes are likely to provide conclusive identification of the primary defects in novel CDGS types that affect the synthesis and transfer of precursor oligosaccharides.
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PMID:Molecular basis of carbohydrate-deficient glycoprotein syndromes type I with normal phosphomannomutase activity. 1057 Oct 10

Dietary mannose is used to treat glycosylation deficient patients with mutations in phosphomannose isomerase (PMI), but there is little information on mannose metabolism in model systems. We chose the mouse as a vertebrate model. Intravenous injection of [2-3H]mannose shows rapid equilibration with the extravascular pool and clearance t(1/2) of 28 min with 95% of the label catabolized via glycolysis in <2 h. Labeled glycoproteins appear in the plasma after 30 min and increase over 3 h. Various organs incorporate [2-3H]mannose into glycoproteins with similar kinetics, indicating direct transport and utilization. Liver and intestine incorporate most of the label (75%), and the majority of the liver-derived proteins eventually appear in plasma. [2-3H]Mannose-labeled liver and intestine organ cultures secrete the majority of their labeled proteins. We also studied the long-term effects of mannose supplementation in the drinking water. It did not cause bloating, diarrhea, abnormal behavior, weight gain or loss, or increase in hemoglobin glycation. Organ weights, histology, litter size, and growth of pups were normal. Water intake of mice given 20% mannose in their water was reduced to half compared to other groups. Mannose in blood increased up to 9-fold (from 100 to 900 microM) and mannose in milk up to 7-fold (from 75 to 500 microM). [2-3H]Mannose clearance, organ distribution, and uptake kinetics and hexose content of glycoproteins in organs were similar in mannose-supplemented and non-supplemented mice. Mannose supplements had little effect on the specific activity of phosphomannomutase (Man-6-P<-->Man-1-P) in different organs, but specific activity of PMI in brain, intestine, muscle, heart and lung gradually increased <2-fold with increasing mannose intake. Thus, long-term mannose supplementation does not appear to have adverse effects on mannose metabolism and mice safely tolerate increased mannose with no apparent ill effects.
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PMID:Studies of mannose metabolism and effects of long-term mannose ingestion in the mouse. 1168 98

Giardia lamblia, which is an important parasitic cause of diarrhea, uses activated forms of glucose to make glycogen and activated forms of mannose to make glycophosphosphoinositol anchors. A necessary step for glucose activation is isomerization of glucose-6-phosphate to glucose-1-phosphate by a phosphoglucomutase (PGM). Similarly, a phosphomannomutase (PMM) converts mannose-6-phosphate to mannose-1-phosphate. While whole genome sequences of Giardia predict two PGM candidates, no PMM candidate is present. The hypothesis tested here is that at least one of the two Giardia PGM candidates has both PGM and PMM activity, as has been described for bacterial PGM orthologs. Nondenaturing gels showed that Giardia has two proteins with PGM activity, one of which also has PMM activity. Phylogenetic analyses showed that one of the two Giardia PGM candidates (Gl-PGM1) shares recent common ancestry with other eukaryotic PGMs, while the other Giardia PGM candidate (Gl-PGM2) is deeply divergent. Both Gl-PGM1 and Gl-PGM2 rescue a Saccharomyces cerevisiae pgm1Delta/pgm2Delta double deletion strain, while only Gl-PGM2 rescues a temperature-sensitive PMM mutant of S. cerevisiae (sec53-ts). Recombinant Gl-PGM1 has PGM activity only, whereas Gl-PGM2 has both PGM and PMM activities. We conclude that Gl-PGM1 behaves as a conventional eukaryotic PGM, while Gl-PGM2 is a novel eukaryotic PGM that also has PMM activity.
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PMID:A deeply divergent phosphoglucomutase (PGM) of Giardia lamblia has both PGM and phosphomannomutase activities. 2050 84