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Inhibition of Phosphorylase‐a by Fructose‐1‐Phosphate, α‐Glycerophosphate and Fructose‐1,6‐Diphosphate: Explanation for Fructose‐Induced Hypoglycaemia in Hereditary Fructose Intolerance and Fructose‐1,6‐Diphosphatase Deficiency *
Author(s) -
Kaufmann U.,
Froesch E. R.
Publication year - 1973
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1973.tb02208.x
Subject(s) - fructose , aldolase b , fructolysis , glycogenolysis , chemistry , fructose 1,6 bisphosphatase , glycogen phosphorylase , biochemistry , endocrinology , medicine , fructose bisphosphate aldolase , aldolase a , enzyme , metabolism
Abstract. The effect of fructose‐1‐phosphate, α‐glycerophosphate and fruetose‐1,6‐diphosphate on the activity of liver phosphorylase‐a has been investigated at different concentrations of inorganic phosphorus.—Inhibition of phosphorylase‐a by fructose‐1‐phosphate is competitive, by α‐glycerophosphate it is noncompetitive and by fructose‐1,6‐diphosphate uncompetitive. The K i is 4 × 10 ‐3 M for fructose‐1‐phosphate and in the range of 5 to 6 × 10 ‐2 M for fructose‐1,6‐diphosphate and α‐glycerophosphate. The activity of phosphorylase‐a and its inhibition by fructose‐1‐phosphate depends very much on the concentration of inorganic phosphorus.—In fructose‐1,6‐diphosphatase deficiency glucose production from gluconeogenic precursors is impossible, whereas in hereditary fructose intolerance accumulated fructose‐1‐phosphate blocks the residual abnormal hepatic aldolase. Our findings explain fructose induced hypoglycaemia in hereditary fructose intolerance and fructose‐1,6‐diphosphatase deficiency by a block in glycogenolysis at the level of phosphorylase‐a.