Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene-induced porphyria.
Uroporphyrinogen decarboxylase is an essential enzyme in all organisms and functions in the heme biosynthetic pathway, catalyzing the decarboxylation of the four acetate groups of uroporphyrinogen to form coproporphyrinogen. This work examines whether the four sequential decarboxylations occur at the same active site, and explores whether hexachlorobenzene-induced porphyria affects the behavior of the enzyme. For this purpose, kinetic competition studies were done with mixtures of uroporphyrinogen III and pentacarboxyporphyrinogen III. With the enzyme from normal rats, a constant velocity was obtained with all the mixtures, indicating that uroporphyrinogen and pentacarboxy-porphyrinogen react at the same active site, i.e. the first and fourth decarboxylations occur at the same site. In contrast, in experiments with enzyme from rats with hexachlorobenzene-induced porphyria, the total rate for mixtures was always lower than the reference rate; and a curve with a deep minimum was obtained, indicating that the two reactions occur at functionally different sites, but with cross-inhibition. This suggests that the modifications induced in the enzyme by hexachlorobenzene cause the two active sites to become nonequivalent and functionally different. The question is discussed how the hexachlorobenzene treatment may produce this abnormal kinetic behavior, and alternative hypotheses are considered.
Chaufan
Gabriela
G
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Corvi
Maria M
MM
San Martín de Viale
Leonor C
LC
Cárdenas
María Luz
ML
Ríos de Molina
María Del Carmen
Mdel C
D000818:Animals; D005260:Female; D006581:Hexachlorobenzene / Q000494:pharmacology* / Q000633:toxicity; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D011164:Porphyrias / Q000139:chemically induced* / Q000201:enzymology*; D011165:Porphyrinogens / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism*; D014577:Uroporphyrinogens / Q000378:metabolism
D011165:Porphyrinogens; D014577:Uroporphyrinogens; C041927:pentacarboxylic porphyrinogen; D006581:Hexachlorobenzene; D014575:Uroporphyrinogen Decarboxylase