Fuel-mediated teratogenesis. Use of D-mannose to modify organogenesis in the rat embryo in vivo.

Buchanan, Thomas A.; Freinkel, Norbert; Lewis, Nancy Jo; Metzger, Boyd E.; Akazawa, Shoichi

doi:10.1172/jci111908

Cited by 27 publications

(16 citation statements)

References 40 publications

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“…Thus, the relative relationships do not favor a significant displacement of glucose by endogenous mannose during fetal life and a consequent perturbation of glycolytic flux ["the Honeybee Syndrome" (13,14)]. On the basis of our experiences with the rat embryo (13)(14)(15), deleterious actions of mannose at the levels of glucose that prevail in human pregnancy would necessitate more than 50-fold greater concentrations of mannose than we found in the present studies. However, we did not examine mannose/glucose relationships during early gestation.…”

Section: Discussionmentioning

confidence: 42%

Relationships between Glucose and Mannose during Late Gestation in Normal Pregnancy and Pregnancy Complicated by Diabetes Mellitus: Concurrent Concentrations in Maternal Plasma and Amniotic Fluid†

Akazawa

Metzger

Freinkel

1986

The Journal of Clinical Endocrinology & Metabolism

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Enzymatic assays were modified to permit sensitive and highly reproducible simultaneous measurements of D-mannose and D-glucose in biological fluids during weeks 34-40 of human pregnancy. Plasma mannose and glucose averaged 9.8 +/- 0.4 (+/- SEM) and 790 +/- 16 micrograms/ml, respectively, after an overnight fast in pregnant women (n = 22) with normal carbohydrate metabolism. Significantly higher plasma mannose levels were found, despite only minor increases in plasma glucose, in pregnant women with relatively well controlled diabetes mellitus after an overnight fast (16.9 +/- 0.6 micrograms/ml mannose; 883 +/- 29 micrograms/ml glucose; n = 31) or 3-4 h after breakfast (15.7 +/- 1.2 micrograms/ml mannose; 1159 +/- 101 micrograms/ml glucose; n = 19). Plasma mannose correlated significantly with plasma glucose in the women with diabetes mellitus, particularly after an overnight fast. Samples of amniotic fluid were also obtained from the gravida with diabetes mellitus to provide some index of simultaneous relationships in utero. Amniotic fluid mannose and glucose averaged 5.9 +/- 0.4 and 302 +/- 24 micrograms/ml, respectively, after an overnight fast and 6.7 +/- 1.3 and 459 +/- 84 micrograms/ml 3-4 h after breakfast. In amniotic fluid, as in plasma, the concurrent levels of mannose and glucose conformed to relatively fixed relationships. Thus, both fetus and mother appear to be exposed to readily demonstrable amounts of mannose during late gestation and the absolute as well as relative abundance of mannose may be increased coincident with faulty maternal glucoregulation. However, since mannose did not exceed 3% of the concurrent concentration of glucose in any instance, it does not seem likely that endogenous levels of circulating mannose can modify glucose utilization appreciably by competing with glucose for phosphorylation via hexokinase and subsequent intracellular processing.

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Section: Discussionmentioning

confidence: 42%

Relationships between Glucose and Mannose during Late Gestation in Normal Pregnancy and Pregnancy Complicated by Diabetes Mellitus: Concurrent Concentrations in Maternal Plasma and Amniotic Fluid†

Akazawa

Metzger

Freinkel

1986

The Journal of Clinical Endocrinology & Metabolism

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“…Mannose can be a life saving therapeutic and a non-antibiotic treatment for selected bacterial infections [3], but in other situations it can be lethal [4] or teratogenic [5], underscoring the importance of stringent regulation of mannose metabolism. In this review, we will discuss mannose origins, metabolism, fate in cells, animals and humans, and its therapeutic applications.…”

Section: Introductionmentioning

confidence: 99%

Mannose metabolism: More than meets the eye

Sharma

Ichikawa

Freeze

2014

Biochemical and Biophysical Research Communications

185

168

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Mannose is a simple sugar with a complex life. It’s a welcome therapy for genetic and acquired human diseases, but it kills honeybees and blinds baby mice. It could cause diabetic complications. Mannose chemistry, metabolism, and metabolomics in cells, tissues and mammals can help explain these multiple systemic effects. Mannose has good, bad or ugly outcomes depending on its steady state levels and metabolic flux. This review describes the role of mannose at cellular level and its impact on organisms.

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“…In humans, PMI deficiency is the cause of carbohydrate-deficient glycoprotein syndrome type Ib (CDG-Ib, OMIM 602579), but the clinical symptoms and aberrant glycosylation can be corrected with dietary Man supplements (Davis et al, 2002). Although Man is beneficial for CDG-Ib patients, it is toxic to honeybees and becomes teratogenic to mid-stage rat embryos when given in high concentrations (Sols et al, 1960;de la Fuente et al, 1986;Freinkel et al, 1984;Moore et al, 1987;Buchanan et al, 1985;DeRossi et al, 2006). The toxicity appears to stem from an accumulation of Man-6-P which cannot efficiently enter glycolysis, instead becoming trapped in a cycle of dephosphorylation and rephosphorylation resulting in depletion of intracellular ATP.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Aspergillus fumigatus phosphomannose isomerase Pmi1 and its impact on cell wall synthesis and morphogenesis

Fang

Wang

et al. 2009

Microbiology

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Phosphomannose isomerase (PMI) is an enzyme catalysing the interconversion of mannose 6-phosphate (Man-6-P) and fructose 6-phosphate (Fru-6-P). The reaction catalysed by PMI is the first committed step in the synthesis of mannose-containing sugar chains and provides a link between glucose metabolism and mannosylation. In this study, the pmi1 gene was identified to encode PMI in the human fungal pathogen Aspergillus fumigatus. Characterization of A. fumigatus Pmi1 expressed in Escherichia coli revealed that this PMI mainly catalysed the conversion of Fru-6-P to Man-6-P and that its binding affinity for Man-6-P was similar to that of yeast PMIs, but different to those of PMIs from bacteria or animals. Loss of pmi1 was lethal unless Man was provided in the growth medium. However, a Dpmi1 mutant cell showed a significantly reduced growth rate at a high concentration of Man. Biochemical analysis revealed that both inadequate and replete Man led to an accumulation of intracellular Man-6-P and a reduction in the amount of a-glucan in the cell wall. Uncoupling of the link between energy production and glycosylation by deletion of the pmi1 gene led to phenotypes such as defects in cell wall integrity, abnormal morphology and reduced conidiation. Our results reveal that PMI activity is essential for viability and plays a central regulatory role in both cell wall synthesis and energy production in A. fumigatus.

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Fuel-mediated teratogenesis. Use of D-mannose to modify organogenesis in the rat embryo in vivo.

Cited by 27 publications

References 40 publications

Relationships between Glucose and Mannose during Late Gestation in Normal Pregnancy and Pregnancy Complicated by Diabetes Mellitus: Concurrent Concentrations in Maternal Plasma and Amniotic Fluid†

Relationships between Glucose and Mannose during Late Gestation in Normal Pregnancy and Pregnancy Complicated by Diabetes Mellitus: Concurrent Concentrations in Maternal Plasma and Amniotic Fluid†

Mannose metabolism: More than meets the eye

Characterization of the Aspergillus fumigatus phosphomannose isomerase Pmi1 and its impact on cell wall synthesis and morphogenesis

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