Effect of fructose 1-phosphate on the activation of liver glycogen synthase.

M Bollen, L Mvumbi, W Stalmans, B Toth… - Biochemical …, 1986 - ncbi.nlm.nih.gov
M Bollen, L Mvumbi, W Stalmans, B Toth, I Farkas, G Bot, P Gergely
Biochemical Journal, 1986ncbi.nlm.nih.gov
The intravenous administration of fructose causes within minutes a massive accumulationof
fructose 1-phosphate in theliver (about 10, umol/g oftissue), with secondary changes in
various metabolic pathways [1]. As far as the effect on glycogen metabolism is concerned,
contradictory resultshave been obtained by various groups of authors (see [2]). Ciudad et
al.[3] reported a simultaneous activation of glycogen synthase and of glycogen
phosphorylase after the addition of fructose to isolated hepatocytes from fasted rats. In this …
The intravenous administration of fructose causes within minutes a massive accumulationof fructose 1-phosphate in theliver (about 10, umol/g oftissue), with secondary changes in various metabolic pathways [1]. As far as the effect on glycogen metabolism is concerned, contradictory resultshave been obtained by various groups of authors (see [2]). Ciudad et al.[3] reported a simultaneous activation of glycogen synthase and of glycogen phosphorylase after the addition of fructose to isolated hepatocytes from fasted rats. In this Journal, Gergely et al.[2] presented an explanation at the enzyme level for the latter observations.(i) Data with crude liver preparations [2] and with purified enzymes [4] indicated that fructose 1-phosphate causes a marked inhibitionofphosphorylasephosphatase. The latter effect is expected to result in a higher steady-state concentrationof phosphorylase a.(ii) The activation of glycogen synthase is strongly inhibited by phosphorylase a ([5], and see Fig. la). However, fructose 1-phosphate was reported to release synthase phosphatase from inhibition by phosphorylase a [2]. Hence the accumulation of fructose 1-phosphate in the liver after fructose injection could explain the simultaneous activation of phosphorylase and of synthase. The group in Leuven has also regularly observed an inhibitory effect of added fructose 1-phosphate (10-20 mM) on theinactivation of phosphorylase in gel-filtered liver extracts, but failed to detect the reported release [2] of synthase phosphataseactivity from the inhibitory effect of phosphorylase a. Analysis of the experimental conditions revealed as the only apparent difference the type of fructose 1-phosphate, which was either a bis-cyclohexylammonium salt* in Debrecen [2] or a sodium salt in Leuven, both obtained from Sigma Chemical Co.(as well as the barium salt). Therefore, the effects of the commercial fructose 1-phosphate salts were compared with those ofcompounds that were transformed from their original form into sodium or potassium salts by passage through Dowex-columns (H+ form) and subsequent neutralization with either NaOH or KOH. The generalexperimental conditions were as described by Gergely et al.[2]. Fructose 1-phosphate was assayed as described [6]. As shown in Fig. 1, the inactivation of phosphorylase in a gel-filtered extract was about equally inhibited by the addition of 20 mm of any tested preparation of fructose 1-phosphate (the bis-cyclohexylammonium salt and the
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