Decay of hexokinase during reticulocyte maturation: is oxidative damage a signal for destruction?
Proteolysis of hexokinase in cell-free systems prepared from rabbit reticulocytes has been shown previously to be ATP-dependent and apparently mediated by the ubiquitin system (Magnani et al. J. Biol.Chem.261, 8327-8333). We have investigated this phenomenon, but found no substantial loss of hexokinase in cell-free systems prepared from fresh lysates. Storage of lysates at -20 degrees C or addition of a free radical generating system was required to demonstrate rapid ATP-dependent decay. It appears that initial oxidative damage to hexokinase does not abolish its activity but allows it to be recognized by an ATP-dependent proteolytic system. The relevance of this mechanism to in vivo degradation of hexokinase is discussed.
Thorburn
D R
DR
Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Beutler
E
E
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D002474:Cell-Free System; D003676:Deferoxamine / Q000494:pharmacology; D004905:Erythrocyte Aging; D005609:Free Radicals; D005947:Glucose / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000097:blood; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000097:blood; D006593:Hexokinase / Q000097:blood*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000097:blood; D010084:Oxidation-Reduction; D011770:Pyruvate Kinase / Q000097:blood; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects / Q000201:enzymology*
D005609:Free Radicals; D002248:Carbon Monoxide; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D006593:Hexokinase; D011770:Pyruvate Kinase; D005947:Glucose; D003676:Deferoxamine