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Abstract:

1. 1. Preliminary experiments with Euglena gracilis indicated that an endogenous factor which modified enzymic synthesis of porphyrinogens from PBG, was present in Homogenates (H) and Supernatant (S) fractions. 2. 2. When H or S was stored at 4-6°C, enzymic activity underwent an apparent spontaneous activation, increasing by as much as 7.5-8 times after 14 and 22 days of aging respectively. 3. 3. Experiments were carried out to detect, isolate and identify this factor. S and H were heated and the effect of the protein free supernatants (Hø,Sø) on activity were tested. By gel filtration of H and S, a low molecular weight compound (FH, FS) was separated, and the activity of the eluated protein (PrH, PrS) was enhanced 10-12 times. 4. 4. Addition of either Hø, Sø, FH or FS to different E. gracilis preparations increased their activities, suggesting the existence of a low molecular weight, heat-stable factor which would act stimulating enzymic synthesis of porphyrinogens. However some differences in the properties of the factor present in Hø or Sø and that present in FH or FS were observed. 5. 5. Studies on the FH and FS, confirmed that the factor was heat-stable, upon storage at 4°C its activation properties were not modified; but they were destroyed by basic or acid treatment. 6. 6. The same degree of activation as that produced by FH and FS on H, S, PrH and PrS, was obtained by replacing the factor solution by 10-7M folic acid or 10-3-10-2M Gluthation (GSH); however, neither the factor nor folic acid or GSH has any effect on the pellet enzyme, either bound to the membrane or solubilized by means of a chaothropic agent. 7. 7. The potential use of this factor in the treatment of acute porphyrias was indirectly investigated, by treating acute intermittent porphyria patients in early or acute attack with folic acid; after its oral administration at a dose of 30 mg daily for not longer than 10 days, both biochemical and clinical recovery followed. 8. 8. A scheme to explain the role of this factor in acting and controlling porphobilinogenase activity in E. gracilis is proposed. © 1981.

Registro:

Documento: Artículo
Título:Porphyrin biosynthesis in Euglena gracilis-IV. An endogenous factor controlling the enzymic synthesis of porphyrinogens and its possible role in the treatment of some porphyrias
Autor:De Geralnik, A.A.J.; Rossetti, M.V.; Del Carmen Batlle, A.M.
Filiación:Centro de Investigaciones sobre Porfirinas y Porfirias-CIPYP, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Casilla de Correo N 53, Sucursal 48, 1448 Buenos Aires, Argentina
Palabras clave:ammonia lyase; Ammonia Lyases; folic acid; glutathione; porphyrin; porphyrinogen; adult; article; biosynthesis; enzyme activation; Euglena gracilis; female; gel chromatography; heat; human; metabolism; molecular weight; porphyria; Adult; Ammonia-Lyases; Chromatography, Gel; Enzyme Activation; Euglena gracilis; Female; Folic Acid; Glutathione; Heat; Human; Molecular Weight; Porphyria; Porphyrinogens; Porphyrins; Support, Non-U.S. Gov't
Año:1981
Volumen:13
Número:3
Página de inicio:343
Página de fin:353
DOI: http://dx.doi.org/10.1016/0020-711X(81)90088-4
Título revista:International Journal of Biochemistry
Título revista abreviado:Int. J. Biochem.
ISSN:0020711X
CODEN:IJBOB
CAS:folic acid, 59-30-3, 6484-89-5; glutathione, 70-18-8; porphyrin, 24869-67-8; porphyrinogen, 4396-11-6; Ammonia-Lyases, EC 4.3.1.; Folic Acid, 59-30-3; Glutathione, 70-18-8; Porphyrinogens; Porphyrins
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_0020711X_v13_n3_p343_DeGeralnik.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0020711X_v13_n3_p343_DeGeralnik

Referencias:

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  • Batlle, Del, Wider de Xifra, Stella, A simple method for measuring erythrocyte porphobilinogenase and its use in the diagnosis of acute intermittent porphyria (1978) Int. J. Biochem., 9, pp. 871-876
  • Battersby, Fookes, Gustaeson-Potter, Matcham, Mcdonald, Proof by synthesis that unrearranged hidroxymethylbilane is the product from deaminase and the substrate for cosynthetase in the biosynthesis of urogen—III (1979) Journal of the Chemical Society, Chemical Communications, pp. 1155-1158
  • Blrton, Fagermess, Hosozawa, Jordan, Scott, 13Cn.m.r. Evidence for a new intermediate, pre-uroporphyrinogen. in the enzymic transformation of porphobilinogen into uroporphyrinogens I and III (1979) Journal of the Chemical Society, Chemical Communications, pp. 202-204
  • Heilmeyer, Clotten, Zur Biochemischen Pathogenese der Porphyria Acuta Intermittens (1969) Klinische Wochenschrift, 47, pp. 71-74
  • Jordan, Burton, Nordlöv, Schneider, Pryde, Scott, Pre-uroporphyrinogen a substrate for uroporphyrinogen—III Cosynthetase (1979) Journal of the Chemical Society, Chemical Communications, pp. 204-205
  • Juknat de, Rossetti, Kotler, Fumagalli, Batlle A.M. del, (1980) Porphyrin biosynthesis in Rh. palustris—V. Studies on the enzymic synthesis of the tetrapyrrole macrocycle, , In preparation
  • Lockwood, Rimington, Purification of an enzyme converting porphobilinogen to uroporphyrinogen (1957) Biochem. J., 67, p. 8
  • Llambi'as, Batlle A.M. del, Uroporphyrinogen III cosynthetase. Evidence of the existence of a polypyrrolic substrate in soybean callus tissue (1970) FEBS Lett., 121, pp. 327-340
  • Piper, Van Lier, Pteridine regulation of inhibition of hepatic uroporphyrinogen—I. Synthetase by lead chloride (1977) Molec. Pharmac., 13, pp. 1126-1135
  • Rossetti, Batlle, Polypyrrole intermediates in porphyrin biosynthesis. Studies with Euglena gracilis (1977) Int. J. Biochem., 8, pp. 277-283
  • Rossetti, Juknat de Geralnik, Batlle, Porphyrin biosynthesis in Euglena gracilis—II. Pyrrlymethane intermediates in the enzymic cyclotetramerization of porphobilinogen (1977) Int. J. Biochem., 8, pp. 781-787
  • Rossetti, Juknat de Geralnik, Batlle A.M. del, (1980) Porphyrin biosynthesis in E. gracilis—IV. Studies on the isolation and purification of the enzymes involved in the cyclotetramerization of PBG, , In preparation
  • Sancovich, Batlle A.M. del, Grinstein, Porphyrin biosynthesis—VI. Separation and purification of porphobilinogen deaminase and uroporphyrinogen isomerase from cow liver. Porphobilinogenase an allosteric enzyme (1969) Biochim. biophys. Acta, 191, pp. 130-143
  • Strand, Felsher, Redeker, Marver, Enzymic abnormality in heme biosynthesis in acute intermittent porphyria: decreased hepatic conversion of porphobilinogen to porphyrins and increased δ-amino levulinic acid synthetase activity (1970) Proc. natn. Acad. Act. U.S.A., 67, pp. 1315-1320
  • Tephly, Identification of a small molecular weight substance that protects uroporphyrinogen—I. Synthetase from the inhibition by lead (1975) Porphyrin in Human Diseases. Report of the Discussions, pp. 128-134. , M. Doss, P. Nawrocki
  • Wider de Xifra, Batlle A.M. del, Stella, Malamud, Simple and short-term therapy of AIP with folic acid (1979) First International Argentine Meeting on Porphyrins and Porphyrias, p. 41. , Buenos Aires
  • Wider de Xifra, Batlle, Stella, Malamud, Acute intermittent porphyria. Another approach to therapy (1980) Int. J. Biochem., 12, pp. 819-822

Citas:

---------- APA ----------
De Geralnik, A.A.J., Rossetti, M.V. & Del Carmen Batlle, A.M. (1981) . Porphyrin biosynthesis in Euglena gracilis-IV. An endogenous factor controlling the enzymic synthesis of porphyrinogens and its possible role in the treatment of some porphyrias. International Journal of Biochemistry, 13(3), 343-353.
http://dx.doi.org/10.1016/0020-711X(81)90088-4
---------- CHICAGO ----------
De Geralnik, A.A.J., Rossetti, M.V., Del Carmen Batlle, A.M. "Porphyrin biosynthesis in Euglena gracilis-IV. An endogenous factor controlling the enzymic synthesis of porphyrinogens and its possible role in the treatment of some porphyrias" . International Journal of Biochemistry 13, no. 3 (1981) : 343-353.
http://dx.doi.org/10.1016/0020-711X(81)90088-4
---------- MLA ----------
De Geralnik, A.A.J., Rossetti, M.V., Del Carmen Batlle, A.M. "Porphyrin biosynthesis in Euglena gracilis-IV. An endogenous factor controlling the enzymic synthesis of porphyrinogens and its possible role in the treatment of some porphyrias" . International Journal of Biochemistry, vol. 13, no. 3, 1981, pp. 343-353.
http://dx.doi.org/10.1016/0020-711X(81)90088-4
---------- VANCOUVER ----------
De Geralnik, A.A.J., Rossetti, M.V., Del Carmen Batlle, A.M. Porphyrin biosynthesis in Euglena gracilis-IV. An endogenous factor controlling the enzymic synthesis of porphyrinogens and its possible role in the treatment of some porphyrias. Int. J. Biochem. 1981;13(3):343-353.
http://dx.doi.org/10.1016/0020-711X(81)90088-4