Tetrapyrroles as substrates and inhibitors of porphyrinogen carboxylyase from rat liver
Porphyrinogen carboxy-lyase is an enzyme of the haem pathway which catalyses the stepwise decarboxylation of porphyrinogens with different number of carboxyl groups. This enzyme has a low substrate specificity since at least 18 porphyrinogens were proved to be decarboxylated by the enzyme. In order...
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todo:paper_NIS18657_v26_n5_p403_SanMartinDeViale2023-10-03T16:46:08Z Tetrapyrroles as substrates and inhibitors of porphyrinogen carboxylyase from rat liver San Martin De Viale, L.C. Aragones, A. Tomio, J.M. uroporphyrinogen decarboxylase animal experiment enzyme inhibition in vitro study liver rat Animal Carboxy-Lyases Comparative Study Liver Porphyrinogens Pyrroles Rats Substrate Specificity Uroporphyrinogen Decarboxylase Porphyrinogen carboxy-lyase is an enzyme of the haem pathway which catalyses the stepwise decarboxylation of porphyrinogens with different number of carboxyl groups. This enzyme has a low substrate specificity since at least 18 porphyrinogens were proved to be decarboxylated by the enzyme. In order to clarify this complex process of decarboxylation, studies were carried out using a purified enzyme preparation from rat liver. The authors studied the behavior of the enzyme in the presence of uroporphyrinogens I, II, III, and IV. The effect of different porphyrins, porphyrinogens and haemin on uroporphyrinogen decarboxylation was also studied to see the influence of nature and position of the side chains of pyrroles as well as the oxidation state in the tetrapyrrolic ring. The liver enzyme decarboxylates the 4 isomers of uroporphyrinogen. The relative accumulation of intermediates porphyrinogens formed was different from that of isomer III. Uroporphyrinogen IV is an efficient substrate for the porphyrinogen carboxy-lyase since it was decarboxylated at higher rate than the normal uroporphyrinogen III. The elimination of a carboxyl group of an acetic acid residue located between an acetic and a propionic acid side chain appears to be easier than the one corresponding to an acetic between 2 propionics or between a methyl and a propionic acid residue. The presence of vicinal propionic side chains in the positions 6 and 7 of the reduced porphyrin ring is an important, but not essential requirement for the binding of the enzyme to porphyrinogen. It was found that coproporphyrinogen III inhibits markedly uroporphyrinogen decarboxylation and that haemin also has inhibitory effect on this reaction. The results of the inhibitory studies suggest one or both of the propionic acid residues located in positions 2 and 4 as important factors in the tetrapyrrole enzyme binding. Some other evidence would indicate that possibly the propionic acid side chain at the position 4 may be particularly important. The reduced state of the tetrapyrrolic ring is essential for the decarboxylation process: thus would allow the side chains to adopt a steric disposition facilitating its binding to the enzyme. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_NIS18657_v26_n5_p403_SanMartinDeViale |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
uroporphyrinogen decarboxylase animal experiment enzyme inhibition in vitro study liver rat Animal Carboxy-Lyases Comparative Study Liver Porphyrinogens Pyrroles Rats Substrate Specificity Uroporphyrinogen Decarboxylase |
| spellingShingle |
uroporphyrinogen decarboxylase animal experiment enzyme inhibition in vitro study liver rat Animal Carboxy-Lyases Comparative Study Liver Porphyrinogens Pyrroles Rats Substrate Specificity Uroporphyrinogen Decarboxylase San Martin De Viale, L.C. Aragones, A. Tomio, J.M. Tetrapyrroles as substrates and inhibitors of porphyrinogen carboxylyase from rat liver |
| topic_facet |
uroporphyrinogen decarboxylase animal experiment enzyme inhibition in vitro study liver rat Animal Carboxy-Lyases Comparative Study Liver Porphyrinogens Pyrroles Rats Substrate Specificity Uroporphyrinogen Decarboxylase |
| description |
Porphyrinogen carboxy-lyase is an enzyme of the haem pathway which catalyses the stepwise decarboxylation of porphyrinogens with different number of carboxyl groups. This enzyme has a low substrate specificity since at least 18 porphyrinogens were proved to be decarboxylated by the enzyme. In order to clarify this complex process of decarboxylation, studies were carried out using a purified enzyme preparation from rat liver. The authors studied the behavior of the enzyme in the presence of uroporphyrinogens I, II, III, and IV. The effect of different porphyrins, porphyrinogens and haemin on uroporphyrinogen decarboxylation was also studied to see the influence of nature and position of the side chains of pyrroles as well as the oxidation state in the tetrapyrrolic ring. The liver enzyme decarboxylates the 4 isomers of uroporphyrinogen. The relative accumulation of intermediates porphyrinogens formed was different from that of isomer III. Uroporphyrinogen IV is an efficient substrate for the porphyrinogen carboxy-lyase since it was decarboxylated at higher rate than the normal uroporphyrinogen III. The elimination of a carboxyl group of an acetic acid residue located between an acetic and a propionic acid side chain appears to be easier than the one corresponding to an acetic between 2 propionics or between a methyl and a propionic acid residue. The presence of vicinal propionic side chains in the positions 6 and 7 of the reduced porphyrin ring is an important, but not essential requirement for the binding of the enzyme to porphyrinogen. It was found that coproporphyrinogen III inhibits markedly uroporphyrinogen decarboxylation and that haemin also has inhibitory effect on this reaction. The results of the inhibitory studies suggest one or both of the propionic acid residues located in positions 2 and 4 as important factors in the tetrapyrrole enzyme binding. Some other evidence would indicate that possibly the propionic acid side chain at the position 4 may be particularly important. The reduced state of the tetrapyrrolic ring is essential for the decarboxylation process: thus would allow the side chains to adopt a steric disposition facilitating its binding to the enzyme. |
| format |
JOUR |
| author |
San Martin De Viale, L.C. Aragones, A. Tomio, J.M. |
| author_facet |
San Martin De Viale, L.C. Aragones, A. Tomio, J.M. |
| author_sort |
San Martin De Viale, L.C. |
| title |
Tetrapyrroles as substrates and inhibitors of porphyrinogen carboxylyase from rat liver |
| title_short |
Tetrapyrroles as substrates and inhibitors of porphyrinogen carboxylyase from rat liver |
| title_full |
Tetrapyrroles as substrates and inhibitors of porphyrinogen carboxylyase from rat liver |
| title_fullStr |
Tetrapyrroles as substrates and inhibitors of porphyrinogen carboxylyase from rat liver |
| title_full_unstemmed |
Tetrapyrroles as substrates and inhibitors of porphyrinogen carboxylyase from rat liver |
| title_sort |
tetrapyrroles as substrates and inhibitors of porphyrinogen carboxylyase from rat liver |
| url |
http://hdl.handle.net/20.500.12110/paper_NIS18657_v26_n5_p403_SanMartinDeViale |
| work_keys_str_mv |
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1807320869821743104 |