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 th...

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Autores principales: Chaufan, G., Corvi, M.M., San Martín De Viale, L.C., Cárdenas, M.L., Ríos De Molina, M.D.C.
Formato: JOUR
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_10956670_v19_n1_p19_Chaufan
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spelling todo:paper_10956670_v19_n1_p19_Chaufan2023-10-03T16:05:22Z Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene-induced porphyria Chaufan, G. Corvi, M.M. San Martín De Viale, L.C. Cárdenas, M.L. Ríos De Molina, M.D.C. Active Site Competition Plot Heme Biosynthesis Hexachlorobenzene Pentacarboxyporphyrinogen Porphyria Cutanea Tarda (PCT) Tetrapyr-role UROD Uroporphyrinogen Decarboxylase acetic acid coproporphyrinogen hexachlorobenzene pentacarboxyporphyrinogen porphyrinogen unclassified drug uroporphyrinogen uroporphyrinogen decarboxylase animal model article chemical reaction decarboxylation enzyme active site enzyme activity enzyme kinetics enzyme mechanism enzyme purification enzyme structure nonhuman porphyria rat Animals Female Hexachlorobenzene Kinetics Liver Porphyrias Porphyrinogens Rats Rats, Wistar Uroporphyrinogen Decarboxylase Uroporphyrinogens 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. © 2005 Wiley Periodicals, Inc. Fil:Chaufan, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Corvi, M.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:San Martín De Viale, L.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ríos De Molina, M.D.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_10956670_v19_n1_p19_Chaufan
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Active Site
Competition Plot
Heme Biosynthesis
Hexachlorobenzene
Pentacarboxyporphyrinogen
Porphyria Cutanea Tarda (PCT)
Tetrapyr-role
UROD
Uroporphyrinogen Decarboxylase
acetic acid
coproporphyrinogen
hexachlorobenzene
pentacarboxyporphyrinogen
porphyrinogen
unclassified drug
uroporphyrinogen
uroporphyrinogen decarboxylase
animal model
article
chemical reaction
decarboxylation
enzyme active site
enzyme activity
enzyme kinetics
enzyme mechanism
enzyme purification
enzyme structure
nonhuman
porphyria
rat
Animals
Female
Hexachlorobenzene
Kinetics
Liver
Porphyrias
Porphyrinogens
Rats
Rats, Wistar
Uroporphyrinogen Decarboxylase
Uroporphyrinogens
spellingShingle Active Site
Competition Plot
Heme Biosynthesis
Hexachlorobenzene
Pentacarboxyporphyrinogen
Porphyria Cutanea Tarda (PCT)
Tetrapyr-role
UROD
Uroporphyrinogen Decarboxylase
acetic acid
coproporphyrinogen
hexachlorobenzene
pentacarboxyporphyrinogen
porphyrinogen
unclassified drug
uroporphyrinogen
uroporphyrinogen decarboxylase
animal model
article
chemical reaction
decarboxylation
enzyme active site
enzyme activity
enzyme kinetics
enzyme mechanism
enzyme purification
enzyme structure
nonhuman
porphyria
rat
Animals
Female
Hexachlorobenzene
Kinetics
Liver
Porphyrias
Porphyrinogens
Rats
Rats, Wistar
Uroporphyrinogen Decarboxylase
Uroporphyrinogens
Chaufan, G.
Corvi, M.M.
San Martín De Viale, L.C.
Cárdenas, M.L.
Ríos De Molina, M.D.C.
Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene-induced porphyria
topic_facet Active Site
Competition Plot
Heme Biosynthesis
Hexachlorobenzene
Pentacarboxyporphyrinogen
Porphyria Cutanea Tarda (PCT)
Tetrapyr-role
UROD
Uroporphyrinogen Decarboxylase
acetic acid
coproporphyrinogen
hexachlorobenzene
pentacarboxyporphyrinogen
porphyrinogen
unclassified drug
uroporphyrinogen
uroporphyrinogen decarboxylase
animal model
article
chemical reaction
decarboxylation
enzyme active site
enzyme activity
enzyme kinetics
enzyme mechanism
enzyme purification
enzyme structure
nonhuman
porphyria
rat
Animals
Female
Hexachlorobenzene
Kinetics
Liver
Porphyrias
Porphyrinogens
Rats
Rats, Wistar
Uroporphyrinogen Decarboxylase
Uroporphyrinogens
description 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. © 2005 Wiley Periodicals, Inc.
format JOUR
author Chaufan, G.
Corvi, M.M.
San Martín De Viale, L.C.
Cárdenas, M.L.
Ríos De Molina, M.D.C.
author_facet Chaufan, G.
Corvi, M.M.
San Martín De Viale, L.C.
Cárdenas, M.L.
Ríos De Molina, M.D.C.
author_sort Chaufan, G.
title Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene-induced porphyria
title_short Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene-induced porphyria
title_full Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene-induced porphyria
title_fullStr Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene-induced porphyria
title_full_unstemmed Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene-induced porphyria
title_sort abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene-induced porphyria
url http://hdl.handle.net/20.500.12110/paper_10956670_v19_n1_p19_Chaufan
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