Impaired hexose uptake by diploid skin fibroblasts from galactosaemic patients. Connection with cell growth and amino acid metabolism, and possible bearing on late-onset clinical symptoms.
In skin fibroblasts of patients presenting with galactosaemia, either from galactose 1-phosphate uridyltransferase or galactokinase deficiency, a deficit in extracellular glucose utilization was observed. This deficit was constant over 3 weeks of continuous cell growth in a medium containing 5.5 mmol/L glucose as the only hexose, and homologous serum. Levels of glucose utilization by deficient skin fibroblasts were stable at about 65-70% of the glucose utilization of control normal skin fibroblasts. Cell morphology was normal, and cell growth was subnormal during this period. However, the energy provision appeared sufficient for cellular needs since cell growth in this glucose medium was observed not to depend on the presence of extracellular glutamine. In contrast, glutamine was required for growth of galactosaemic fibroblasts cultured in medium containing 5.5 mmol/L galactose. If expressed in many cell types, this impaired glucose uptake would be expected seriously to damage highly glucose-dependent tissues such as the central nervous system. This might be of relevance to the persistent neurological damage observed in many galactosaemic patients in spite of their compliance with an early strict galactose-free diet.
Wolfrom
C
C
INSERM U56, Hôpital de Bicêtre, Le Kremlin, France.
Raynaud
N
N
Kadhom
N
N
Poggi
J
J
Soni
T
T
Gautier
M
M
D000293:Adolescent; D000596:Amino Acids / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002239:Carbohydrate Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005690:Galactose / Q000378:metabolism / Q000633:toxicity; D005693:Galactosemias / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006601:Hexoses / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007773:Lactates / Q000096:biosynthesis / Q000378:metabolism; D012867:Skin / Q000378:metabolism*
D000596:Amino Acids; D001786:Blood Glucose; D006601:Hexoses; D007773:Lactates; D005974:Glutamate-Ammonia Ligase; D005947:Glucose; D005690:Galactose