Glucose 6-phosphate transport in fibroblast microsomes from glycogen storage disease type 1b patients: evidence for multiple glucose 6-phosphate transport systems.
In liver endoplasmic reticulum the intralumenal glucose-6-phosphatase activity requires the operation of a glucose 6-phosphate transporter (G6PT1). Mutations in the gene encoding G6PT1 cause glycogen storage disease type 1b, which is characterized by a loss of glucose-6-phosphatase activity and impaired glucose homoeostasis. We describe a novel glucose 6-phosphate (G6P) transport activity in microsomes from human fibroblasts and HeLa cells. This transport activity is unrelated to G6PT1 since: (i) it was similar in microsomes of skin fibroblasts from glycogen storage disease type 1b patients homozygous for mutations of the G6PT1 gene, and in microsomes from human control subjects; (ii) it was insensitive to the G6PT1 inhibitor chlorogenic acid; and (iii) it was equally active towards G6P and glucose 1-phosphate, whereas G6PT1 is highly selective for G6P. Taken together, our results provide evidence for the presence of multiple transporters for G6P (and other hexose phosphoesters) in the endoplasmic reticulum.
Leuzzi
R
R
Dipartimento di Fisiopatologia e Medicina Sperimentale, Università di Siena, Viale A. Moro no. 1, 53100-Siena, Italy.
Fulceri
R
R
Marcolongo
P
P
Bánhegyi
G
G
Zammarchi
E
E
Stafford
K
K
Burchell
A
A
Benedetti
A
A
D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D002726:Chlorogenic Acid / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism*; D005953:Glycogen Storage Disease Type I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D012016:Reference Values; D012867:Skin / Q000378:metabolism*
D017920:Antiporters; D009004:Monosaccharide Transport Proteins; C503531:SLC37A4 protein, human; C111261:glucose 6-phosphate(transporter); D002726:Chlorogenic Acid; D019298:Glucose-6-Phosphate; D005952:Glucose-6-Phosphatase; D005947:Glucose