Dataset Information

Phosphoglucomutase Is Not the Target for Galactose Toxicity in Plants.

ABSTRACT: Plants synthesize a number of different oligomeric or polymeric sugars containing galactose. During growth and development some of these carbohydrates are metabolized or remodeled releasing galactose as a breakdown product. All plants have established recycling pathways for such sugars, for which they seem to have a limited capacity to cope with. Exceeding these limits results in sugar toxicity, which is observed already at concentrations as low as 1 mmol·l-1 for galactose. The mechanism of galactose toxicity is poorly understood but it seems plausible that the enzymes involved in carbohydrate metabolism also might be the targets responsible for the adverse effects. Data from yeast and bacteria suggests that the enzyme phosphoglucomutase (PGM) is inhibited by galactose-1-phosphate. To test this hypothesis for plants we expressed recombinant cytosolic PGM3 from Arabidopsis in E. coli. Intriguingly, the enzyme was not inhibited by galactose-1-phosphate at physiological concentrations. Furthermore, PGM3 did not convert galactose-1-phosphate to galactose-6-phosphate, which was suggested as the inhibitory mode of action in yeast. In addition, metabolite levels in Arabidopsis roots were analyzed for their galactose-1-phosphate concentration by means of GC-MS. Seedlings grown on MS-media with sucrose contained less than 10 nmol·g FW-1 of galactose-1-phosphate. However, seedlings from plates, in which the sucrose was replaced by galactose, showed a strong increase of Gal-1-P to levels of up to 200 nmol·g FW-1.

SUBMITTER: Althammer M

PROVIDER: S-EPMC7059798 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Phosphoglucomutase Is Not the Target for Galactose Toxicity in Plants.

Althammer Martina M Blöchl Constantin C Reischl Roland R Huber Christian G CG Tenhaken Raimund R

Frontiers in plant science 20200228

Plants synthesize a number of different oligomeric or polymeric sugars containing galactose. During growth and development some of these carbohydrates are metabolized or remodeled releasing galactose as a breakdown product. All plants have established recycling pathways for such sugars, for which they seem to have a limited capacity to cope with. Exceeding these limits results in sugar toxicity, which is observed already at concentrations as low as 1 mmol·l<sup>-1</sup> for galactose. The mechan ...[more]

PMID: 32180781

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Project description:We recently redefined phosphoglucomutase-1 deficiency not only as an enzyme defect, involved in normal glycogen metabolism, but also an inborn error of protein glycosylation. Phosphoglucomutase-1 is a key enzyme in glycolysis and glycogenesis by catalyzing in the bidirectional transfer of phosphate from position 1 to 6 on glucose. Glucose-1-P and UDP-glucose are closely linked to galactose metabolism. Normal PGM1 activity is important for effective glycolysis during fasting. Activated glucose and galactose are essential for normal protein glycosylation. The complex defect involving abnormal concentrations of activated sugars leads to hypoglycemia and two major phenotypic presentations, one with primary muscle involvement and the other with severe multisystem disease. The multisystem phenotype includes growth delay and malformations, like cleft palate or uvula, and liver, endocrine and heart function with possible cardiomyopathy. The patients have normal intelligence. Decreased transferrin galactosylation is a characteristic finding on mass spectrometry. Previous in vitro studies in patient fibroblasts showed an improvement of glycosylation on galactose supplements. Four patients with PGM1 deficiency have been trialed on d-galactose (compassionate use), and showed improvement of serum transferrin hypoglycosylation. There was a parallel improvement of liver function, endocrine abnormalities and a decrease in the frequency of hypoglycemic episodes. No side effects have been observed. Galactose supplementation didn't seem to resolve all clinical symptoms. Adding complex carbohydrates showed an additional clinical amelioration. Based on the available clinical data we suggest to consider the use of 0.5-1g/kg/day d-galactose and maximum 50 g/day oral galactose therapy in PGM1-CDG. The existing data on galactose therapy have to be viewed as preliminary observations. A prospective multicenter trial is ongoing to evaluate the efficacy and optimal d-galactose dose of galactose supplementation.

Dataset Information

Phosphoglucomutase Is Not the Target for Galactose Toxicity in Plants.

Publications

Phosphoglucomutase Is Not the Target for Galactose Toxicity in Plants.

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