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Comparative study of protoporphyrins in erythropoietic protoporphyria and griseofulvin-induced murine protoporphyria. Binding affinities, distribution, and fluorescence spectra in various blood fractions.
J Clin Invest. 1977 Aug; 60(2):380-9.JCI

Abstract

Excess erythrocyte protoporphyrins of human congenital erythropoietic protoporphyria and of griseofulvin-induced murine hepatic protoporphyria were found to be associated with hemoglobin and stroma fractions in similar relationships. More than 99.5% of total erythrocyte protoporphyrin was bound to hemoglobin in each case. However, profound differences were found when protoporphyrin concentration was measured in erythrocytes that had been segregated into populations of progressive age on discontinuous density gradients. In erythropoietic protoporphyria, porphyrin content diminished rapidly with age; in murine protoporphyria, the aging erythrocyte populations became progressively more porphyrin rich. In vitro diffusion of protoporphyrin from plasma across the intact erythrocyte membrane was demonstrated. The equimolar binding affinity of protoporphyrin to hemoglobin was shown to be 40 times that of protoporphyrin to serum albumin. This strong affinity provides the driving force for the observed transmembrane diffusion, and explains the high erythrocyte/plasma porphyrin ratio in murine hepatic protoporphyria. The opposite rapid efflux of intra-erythrocytic protoporphyrin into plasma previously shown in uncomplicated erythropoietic protoporphyria occurs despite this strong hemoglobin affinity, implying continuous efficient clearance of protoporphyrin from plasma by the liver. Furthermore, these and other data suggest that a hepatic synthetic source for any significant fraction of the blood protoporphyrin in erythropoietic protoporphyria is highly improbable.

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

874098

Citation

Poh-Fitzpatrick, M B., and A A. Lamola. "Comparative Study of Protoporphyrins in Erythropoietic Protoporphyria and Griseofulvin-induced Murine Protoporphyria. Binding Affinities, Distribution, and Fluorescence Spectra in Various Blood Fractions." The Journal of Clinical Investigation, vol. 60, no. 2, 1977, pp. 380-9.
Poh-Fitzpatrick MB, Lamola AA. Comparative study of protoporphyrins in erythropoietic protoporphyria and griseofulvin-induced murine protoporphyria. Binding affinities, distribution, and fluorescence spectra in various blood fractions. J Clin Invest. 1977;60(2):380-9.
Poh-Fitzpatrick, M. B., & Lamola, A. A. (1977). Comparative study of protoporphyrins in erythropoietic protoporphyria and griseofulvin-induced murine protoporphyria. Binding affinities, distribution, and fluorescence spectra in various blood fractions. The Journal of Clinical Investigation, 60(2), 380-9.
Poh-Fitzpatrick MB, Lamola AA. Comparative Study of Protoporphyrins in Erythropoietic Protoporphyria and Griseofulvin-induced Murine Protoporphyria. Binding Affinities, Distribution, and Fluorescence Spectra in Various Blood Fractions. J Clin Invest. 1977;60(2):380-9. PubMed PMID: 874098.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative study of protoporphyrins in erythropoietic protoporphyria and griseofulvin-induced murine protoporphyria. Binding affinities, distribution, and fluorescence spectra in various blood fractions. AU - Poh-Fitzpatrick,M B, AU - Lamola,A A, PY - 1977/8/1/pubmed PY - 1977/8/1/medline PY - 1977/8/1/entrez SP - 380 EP - 9 JF - The Journal of clinical investigation JO - J Clin Invest VL - 60 IS - 2 N2 - Excess erythrocyte protoporphyrins of human congenital erythropoietic protoporphyria and of griseofulvin-induced murine hepatic protoporphyria were found to be associated with hemoglobin and stroma fractions in similar relationships. More than 99.5% of total erythrocyte protoporphyrin was bound to hemoglobin in each case. However, profound differences were found when protoporphyrin concentration was measured in erythrocytes that had been segregated into populations of progressive age on discontinuous density gradients. In erythropoietic protoporphyria, porphyrin content diminished rapidly with age; in murine protoporphyria, the aging erythrocyte populations became progressively more porphyrin rich. In vitro diffusion of protoporphyrin from plasma across the intact erythrocyte membrane was demonstrated. The equimolar binding affinity of protoporphyrin to hemoglobin was shown to be 40 times that of protoporphyrin to serum albumin. This strong affinity provides the driving force for the observed transmembrane diffusion, and explains the high erythrocyte/plasma porphyrin ratio in murine hepatic protoporphyria. The opposite rapid efflux of intra-erythrocytic protoporphyrin into plasma previously shown in uncomplicated erythropoietic protoporphyria occurs despite this strong hemoglobin affinity, implying continuous efficient clearance of protoporphyrin from plasma by the liver. Furthermore, these and other data suggest that a hepatic synthetic source for any significant fraction of the blood protoporphyrin in erythropoietic protoporphyria is highly improbable. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/874098/Comparative_study_of_protoporphyrins_in_erythropoietic_protoporphyria_and_griseofulvin_induced_murine_protoporphyria__Binding_affinities_distribution_and_fluorescence_spectra_in_various_blood_fractions_ L2 - https://doi.org/10.1172/JCI108787 DB - PRIME DP - Unbound Medicine ER -