Inhibition of glycolytic enzymes by endogenous aldehydes: a possible relation to diabetic neuropathies.
Endogenous saturated and unsaturated aldehydes were found in significant elevations in serum of diabetic humans and rats. These compounds, originating from the lipid peroxidation processes, are shown here to be potent inhibitors of the glycolytic enzymes, phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. The inhibition process is non-competitive and progressive. The aldehyde mixture, when supplemented to the standard rat diet at 1/100 ratio, caused nerve damage that is reminiscent of diabetic polyneuropathies.
Novotny
M V
MV
Department of Chemistry, Indiana University, Bloomington 47405.
Yancey
M F
MF
Stuart
R
R
Wiesler
D
D
Peterson
R G
RG
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D003929:Diabetic Neuropathies / Q000201:enzymology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors*; D006019:Glycolysis; D006801:Humans; D007700:Kinetics; D009132:Muscles / Q000201:enzymology / Q000294:innervation; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000447:Aldehydes; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010732:Phosphofructokinase-1