ATP modifications in hexokinase deficient fibroblasts exposed to nutrient shifts.
Human fibroblasts from a patient homozygous for hexokinase (HK) deficiency and normal controls were submitted to different nutrient shifts to investigate the role of glucose metabolism on ATP levels. HK-deficient cells maintained in the presence of both glucose and L-glutamine had 20 per cent less ATP than controls and an ATP/ADP ratio of 18 instead of 37-40. Glucose alone was not able to maintain normal ATP levels neither in the controls nor in the HK-deficient cells. However while in control cells the ATP/ADP ratio was not modified, it was reduced to 10 in HK deficiency. The effect of several hexoses on ATP levels was also investigated. Mannose, which is metabolized by HK phosphorylation, was the least efficient for ATP maintenance in HK-deficient cells. In contrast galactose, which is metabolized by a specific galactokinase, provided ATP values close to those observed in the presence of glutamine. These results suggest that glucose metabolism is an important determinant in the maintenance of ATP levels in cultured cells and that glutamine, although being a good metabolic substrate, is not sufficient to maintain normal ATP concentrations.
Istituto di Chimica Biologica G. Fornaini, Università degli Studi, Urbino, Italy.
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Chiarantini
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Vittoria
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Magnani
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006593:Hexokinase / Q000172:deficiency*; D006801:Humans; D009752:Nutritional Status
D005973:Glutamine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006593:Hexokinase; D005947:Glucose