Human erythrocyte delta-aminolevulinate dehydratase inhibition by monosaccharides is not mediated by oxidation of enzyme sulfhydryl groups.
The heme pathway enzyme delta-aminolevulinate dehydratase is a good marker for oxidative stress and metal intoxication. This sulfhydryl enzyme is inhibited in such oxidative pathologies as lead, mercury and aluminum intoxication, exposure to selenium organic species and diabetes. Oxidative stress is a complicating factor in diabetes, inducing non-enzymatic glucose-mediated reactions that change protein structures and impair enzyme functions. We have studied the effects of high glucose, fructose and ribose concentrations on delta-ALA-D activity in vitro. These reducing sugars inhibited delta-ALA-D with efficacies in the order fructose=ribose>glucose. The possible mechanism of glucose inhibition was investigated using lysine, DTT, and t-butylamine. Oxidation of the enzyme's critical sulfhydryl groups was not involved because DTT had no effect. We concluded that high concentrations of reducing sugars or their autoxidation products inhibit delta-ALA-D by a mechanism not related to thiol oxidation. Also, we are not able to demonstrate that the formation of a Schiff base with the critical lysine residue of the enzyme is involved in the inhibition of delta-ALA-D by hexoses.
Gabriel
D
D
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil.
Pivetta
L
L
Folmer
V
V
Soares
J C M
JC
Augusti
G R
GR
Nogueira
C W
CW
Zeni
G
G
Rocha
J B T
JB
D002082:Butylamines / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology*; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D008239:Lysine / Q000494:pharmacology; D008297:Male; D010084:Oxidation-Reduction; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors* / Q000097:blood; D012266:Ribose / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013549:Sweetening Agents / Q000494:pharmacology
D002082:Butylamines; D013438:Sulfhydryl Compounds; D013549:Sweetening Agents; D005632:Fructose; D012266:Ribose; D000623:Porphobilinogen Synthase; D005947:Glucose; D008239:Lysine; D004229:Dithiothreitol