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Abstract:

The biosynthesis of uroporphyrinogen III, the precursor of hemes, chlorophylls, corrins and related structures, is catalyzed by the porphobilinogenase system (PBGase), a complex of two enzymes, PBG-Deaminase (PBG-D) and Isomerase. Although the separate enzymes have been studied in some detail less work has been performed on the properties of the complex. In this study the kinetic behaviour of the enzyme PBGase in a normal yeast strain, D273-10B, and its derivative B231 has been investigated. Uroporphyrinogen formation was linear with time up to 2 hr at 37°C. The enzyme complex shows classical Michaelis-Menten kinetics. From the double reciprocal plots kinetic parameters were estimated for PBGase and PBG-D. Porphyrins were found to be competitive inhibitors with respect to porphobilinogen (PBG) and these compounds appeared to act as inhibitors by forming dead-end complexes with the free enzyme. 5-Aminolevulinic acid (ALA) also inhibited PBGase and this inhibition was overcome by addition of levulinic acid (2μM). These results indicate that ALA, is not an inhibitor but acts through its conversion into porphyrins which are the true inhibitors. © 1994.

Registro:

Documento: Artículo
Título:Inhibition of porphobilinogenase by porphyrins in Saccharomyces cerevisiae
Autor:Araujo, L.S.; Lombardo, M.E.; Del C. Batlle, A.M.
Filiación:Centro de Investigaciones sobre Porfirinas y Porfirias, CIPYP (CONICET-FCEN), UBA Ciudad Universitaria Pabellon II, 2do Piso, CP 1428 Buenos Aires, Argentina
Palabras clave:Porphobilinogenase Porphyrins Aminolevulinic acid-inhibition Saccharomyces cerevisial Kinetics; aminolevulinic acid; porphobilinogenase; porphyrin; unclassified drug; article; controlled study; enzyme inhibition; enzyme kinetics; nonhuman; saccharomyces cerevisiae; Aminolevulinic Acid; Ammonia-Lyases; Kinetics; Porphyrins; Saccharomyces cerevisiae; Support, Non-U.S. Gov't
Año:1994
Volumen:26
Número:12
Página de inicio:1377
Página de fin:1381
DOI: http://dx.doi.org/10.1016/0020-711X(94)90180-5
Título revista:International Journal of Biochemistry
Título revista abreviado:Int. J. Biochem.
ISSN:0020711X
CODEN:IJBOB
CAS:aminolevulinic acid, 106-60-5; porphobilinogenase, 9055-40-7; porphyrin, 24869-67-8; Aminolevulinic Acid, 106-60-5; Ammonia-Lyases, EC 4.3.1.; porphobilinogenase, EC 5.-; Porphyrins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0020711X_v26_n12_p1377_Araujo

Referencias:

  • Afonso, Chinarro Familiar, Stella, Batlle A.M. del, Lecnzner, Magnin, Uroporfirinogeno decarboxilasa eritrocitaria y hepatica en porfiria cutanea tardia (1985) Rev. Arg. Derm., 66, pp. 12-24
  • Araujo, Porphyrin biosynthesis in a wild and its heme-deficient mutant strain of S. cerevisiae (1992) Ph. D. Thesis, , University of Buenos Aires (UBA)
  • Araujo, Lombarde, Rossetti, Batlle A.M. del, Saccharomyces cerevisiae porphobilinogenase: some physical and kinetic properties (1989) Comp. Biochem. Physiol., 92 B, pp. 297-301
  • Battersby, Fookes, Gustafsob-Potter, McDonald, Matcham, Biosynthesis of porphyrins and related macrocycles Part 17 Chemical and enzymic transformation of isomeric aminomethylbilanes into uroporphyrinogens proof that unrearranged bilane is the preferred enzymic substrate and detection of a transient intermediate (1982) Journal of the Chemical Society, Perkin Transactions 1, 1, pp. 2413-2426
  • Battersby, Fookes, Hart, Matcham, Pandey, Biosynthesis of porphyrins and related macrocycles Part 21 The interaction of deaminase and its product (hydroxymethylbilane) and the relationship between deaminase and cosynthetase (1983) Journal of the Chemical Society, Perkin Transactions 1, 1, pp. 3041-3047
  • Borralho, Malamud, Panek, Tenan, Oliveira, Mattoon, Parallel changes in catabolite repression of haem biosynthesis and cytochromes in repression-resistant mutant of Saccharomyces cerevisiae (1989) J. Gen. Microbiol., 135, pp. 1217-1227
  • Correa Garcia, Bermudez Moretti, Cardalda, Rossetti, Batlle A.M. del, The role of ALA-S and ALA-D in regulating porphyrin biosynthesis in a normal and a HEM R+ mutant strain of Saccharomyces cerevisiae (1993) Yeast, 9, pp. 165-173
  • Elder, Acquired disorders of haem synthesis (1976) Essays Med. Biochem., 2, pp. 75-114
  • Fumagalli, Kotler, Rossetti, Batlle A.M. del, Studies on uroporphyrinogen biosynthesis in pig liver (1991) Z. Naturforsch., 46 C, pp. 1101-1108
  • Juknat, Kotler, Koopmann, Batlle A.M. del, Porphobilinogenase from Rhodopseudomonas palusiris (1989) Comp. Biochem. Physiol., 92 B, pp. 291-295
  • Kotler, Fumagalli, Juknat, Batlle A.M. del, Porphyrin biosynthesis in Rp. palus- Iris—IX. PBG-deaminase. Kinetic studies (1987) Int. J. Biochem., 19 (10), pp. 981-985
  • Llambias, Batlle A.M. del, Studies on the porphobilinogen deaminase-uroporphyrinogen cosynthetase system of cultured soybean cells (1971) Biochem J, 121, pp. 327-340
  • Llambias, Batlle A.M. del, Porphyrin biosynthesis—VIII Avian erythrocyte porphobilinogen deaminase-uroporphyrinogen III cosynthetase Its purification properties and the separation of its components (1971) Biochim Biophys Acta, 227, pp. 180-191
  • Rimington, Spectral-absorption coefficients of some porphyrins in the Soret-band region (1960) Biochem J, 75, pp. 620-623
  • Sancovich, Batlle A.M. del, Grinstein, Porphyrin biosynthesis—VI. Separation and purification of porphobilinogen deaminase and uroporphyrinogen isomerase from cow liver. Porphobilinogenase as an allosteric enzyme (1969) Biochim. biophys. Acta, 191, pp. 130-143
  • Williams, Morgan, McDonald, Battersby, Purification of porphobilinogen deaminase from Euglena gracilis and studies of its kinetics (1981) Biochem. J., 193, pp. 301-310

Citas:

---------- APA ----------
Araujo, L.S., Lombardo, M.E. & Del C. Batlle, A.M. (1994) . Inhibition of porphobilinogenase by porphyrins in Saccharomyces cerevisiae. International Journal of Biochemistry, 26(12), 1377-1381.
http://dx.doi.org/10.1016/0020-711X(94)90180-5
---------- CHICAGO ----------
Araujo, L.S., Lombardo, M.E., Del C. Batlle, A.M. "Inhibition of porphobilinogenase by porphyrins in Saccharomyces cerevisiae" . International Journal of Biochemistry 26, no. 12 (1994) : 1377-1381.
http://dx.doi.org/10.1016/0020-711X(94)90180-5
---------- MLA ----------
Araujo, L.S., Lombardo, M.E., Del C. Batlle, A.M. "Inhibition of porphobilinogenase by porphyrins in Saccharomyces cerevisiae" . International Journal of Biochemistry, vol. 26, no. 12, 1994, pp. 1377-1381.
http://dx.doi.org/10.1016/0020-711X(94)90180-5
---------- VANCOUVER ----------
Araujo, L.S., Lombardo, M.E., Del C. Batlle, A.M. Inhibition of porphobilinogenase by porphyrins in Saccharomyces cerevisiae. Int. J. Biochem. 1994;26(12):1377-1381.
http://dx.doi.org/10.1016/0020-711X(94)90180-5