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Citations to this article

Allosteric inhibition of human lymphoblast and purified porphobilinogen deaminase by protoporphyrinogen and coproporphyrinogen. A possible mechanism for the acute attack of variegate porphyria.
P Meissner, … , P Adams, R Kirsch
P Meissner, … , P Adams, R Kirsch
Published April 1, 1993
Citation Information: J Clin Invest. 1993;91(4):1436-1444. https://doi.org/10.1172/JCI116348.
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Allosteric inhibition of human lymphoblast and purified porphobilinogen deaminase by protoporphyrinogen and coproporphyrinogen. A possible mechanism for the acute attack of variegate porphyria.

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Abstract

Variegate porphyria (VP) is characterized by photocutaneous lesions and acute neuropsychiatric attacks. Decreased protoporphyrinogen oxidase activity results in accumulation of protoporphyrin (ogen) IX and coproporphyrin (ogen) III. During acute attacks delta-aminolevulinic acid and porphobilinogen also increase, suggesting that porphobilinogen deaminase (PBG-D) may be rate limiting. We have examined the effects of porphyrinogens accumulating in VP on PBG-D activity in Epstein-Barr virus-transformed lymphoblast sonicates from 12 VP and 12 control subjects. Protoporphyrinogen oxidase activity was decreased and protoporphyrin increased in VP lymphoblasts. PBG-D in control lymphoblasts obeyed Michaelis-Menten kinetics (Vmax 28.7 +/- 1.8 pmol/mg per h, Hill coefficient 0.83 +/- 0.07). VP sonicates yielded sigmoidal substrate-velocity curves that did not obey Michaelis-Menten kinetics. Vmax was decreased (21.2 +/- 2.0 pmol/mg per h) and the Hill coefficient was 1.78 +/- 0.17. Addition of protoporphyrinogen IX and coproporphyrinogen III to control sonicates yielded sigmoidal PBG-D substrate-velocity curves and decreased PBG-D Vmax. Addition of porphyrins or uroporphyrinogen III did not affect PBG-D activity. Removal of endogenous porphyrin (ogens) from VP sonicates restored normal PBG-D kinetics. Purified human erythrocyte PBG-D obeyed Michaelis-Menten kinetics (Vmax 249 +/- 36 nmol/mg per h, Km 8.9 +/- 1.5 microM, Hill coefficient 0.93 +/- 0.14). Addition of protoporphyrinogen yielded a sigmoidal curve with decreased Vmax. The Hill coefficient approached 4. These findings provide a rational explanation for the increased delta-aminolevulinic acid and porphobilinogen during acute attacks of VP.

Authors

P Meissner, P Adams, R Kirsch

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Year: 2021 2020 2019 2018 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 Total
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Citations to this article (47)

Title and authors Publication Year
Laboratory Diagnosis of Porphyria
ED Pierro, MD Canio, R Mercadante, M Savino, F Granata, D Tavazzi, AM Nicolli, A Trevisan, S Marchini, S Fustinoni
Diagnostics 2021
mRNA-based therapy in a rabbit model of variegate porphyria offers new insights into the pathogenesis of acute attacks
D Jericó, KM Córdoba, L Jiang, C Schmitt, M Morán, A Sampedro, M Alegre, M Collantes, E Santamaría, E Alegre, C Culerier, AE de Mendoza, J Oyarzabal, MA Martín, I Peñuelas, MA Ávila, L Gouya, PG Martini, A Fontanellas
Molecular Therapy — Nucleic Acids 2021
Novel treatment options for acute hepatic porphyrias
B Wang
Current Opinion in Gastroenterology 2021
Unexpected presentation of acute porphyria
CK Kiew, AS Lam
BMJ case reports 2021
Acute hepatic porphyria and anaesthesia: a practical approach to the prevention and management of acute neurovisceral attacks
N Wilson-Baig, M Badminton, D Schulenburg-Brand
2021
Treatment with assisted reproduction technologies in women with acute hepatic porphyria
D Vassiliou, AL Hirschberg, E Sardh
Acta Obstetricia et Gynecologica Scandinavica 2021
The acute hepatic porphyrias
B Wang
Translational Gastroenterology and Hepatology 2021
A Pharmacological Chaperone Therapy for Acute Intermittent Porphyria
HJ Bustad, K Toska, C Schmitt, M Vorland, L Skjærven, JP Kallio, S Simonin, P Letteron, J Underhaug, S Sandberg, A Martinez
Molecular Therapy 2020
Clinical Guide and Update on Porphyrias
U Stölzel, MO Doss, D Schuppan
Gastroenterology 2019
Not Your Ordinary Rash
GR Williams, RD Nerenz
Clinical chemistry 2019
Acute hepatic porphyrias: Current diagnosis & management
KE Anderson
Molecular Genetics and Metabolism 2019
Porphyrien – was ist gesichert?
U Stölzel, I Kubisch, T Stauch
Der Internist 2018
Porphyrias and photosensitivity: pathophysiology for the clinician
L Kakoullis, S Louppides, E Papachristodoulou, G Panos
Postgraduate Medicine 2018
Molecular analysis of 19 Spanish patients with mixed porphyrias
MJ Corte, FJ Rubio, MJ Jiménez, SD Díaz, FJ Fernandez, I García, RE de Salamanca, M Méndez
European Journal of Medical Genetics 2018
Inborn Metabolic Diseases
JM Saudubray, MR Baumgartner, J Walter
Inborn Metabolic Diseases 2016
Update review of the acute porphyrias
PE Stein, MN Badminton, DC Rees
British Journal of Haematology 2016
Red-Brown Urine in a Patient with Chronic HIV Infection and Quadriparesis
NM Oosthuizen, J Olivier, J Martins, C Schutte, TS Pillay
Clinical chemistry 2016
Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease
R Schiffmann
Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease 2015
The Cutaneous Porphyrias
D Schulenburg-Brand, R Katugampola, AV Anstey, MN Badminton
Dermatologic Clinics 2014
Management of acute intermittent porphyria
P Harper, E Sardh
Expert Opinion on Orphan Drugs 2014
Partial protoporphyrinogen oxidase (PPOX) gene deletions, due to different Alu-mediated mechanisms, identified by MLPA analysis in patients with variegate porphyria
M Barbaro, M Kotajärvi, P Harper, Y Floderus
Orphanet Journal of Rare Diseases 2013
Antioxidants restore protoporphyrinogen oxidase in variegate porphyria patients
MD Ferrer, P Tauler, A Sureda, C Palacín, JA Tur, A Pons
European Journal of Clinical Investigation 2013
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics
EJ Lamb, CP Price
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics 2012
Handbook of Clinical Neurology
T Ashizawa, PS Sarkar
Muscular Dystrophies 2011
Identification of an AluY-mediated deletion of exon 5 in the CPOX gene by MLPA analysis in patients with hereditary coproporphyria
M Barbaro, M Kotajärvi, P Harper, Y Floderus
Clinical Genetics 2011
The neurologic manifestations of the acute porphyrias
NG Simon, GK Herkes
Journal of Clinical Neuroscience 2011
Rook's Textbook of Dermatology
JA McGrath, J Uitto
Rook's Textbook of Dermatology 2010
Tetrapyrroles
MJ Warren, AG Smith
2009
Dominant versus recessive: Molecular mechanisms in metabolic disease
J Zschocke
Journal of Inherited Metabolic Disease 2008
Class 2 · Transferases VI
D Schomburg, I Schomburg, A Chang
2007
Biosynthesis of heme in mammals
RS Ajioka, JD Phillips, JP Kushner
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2006
The Porphyrin Handbook
PM Shoolingin-Jordan
The Porphyrin Handbook 2003
Clinical and biochemical characteristics and genotype–phenotype correlation in Finnishvariegate porphyria patients
M Fraunberg, K Timonen, P Mustajoki, R Kauppinen
European Journal of Human Genetics 2002
Celiac disease in patients with variegate porphyria.
Twaddle S, Wassif WS, Deacon AC, Peters TJ
Digestive Diseases and Sciences 2001
Multiple Regulatory Steps in Erythroid Heme Biosynthesis
SI Woodard, HA Dailey
Archives of Biochemistry and Biophysics 2000
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U Gross, GF Hoffmann, MO Doss
Journal of Inherited Metabolic Disease 2000
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P Böger, K Wakabayashi
1999
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MB MD
Clinics in Dermatology 1998
Molecular analysis reveals a high mutation frequency in the first untranslated exon of the PPOX gene and largely excludes variegate porphyria in a subset of clinically affected Afrikaner families
MJ Kotze, JN Villiers, JZ Groenewald, RN Rooney, O Loubser, R Thiart, CJ Oosthuizen, MM Niekerk, IM Groenewald, AE Retief, L Warnich
Molecular and Cellular Probes 1998
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CA Cardalda, AA Juknat, FG Princ, A Batlle
Archives of Biochemistry and Biophysics 1997
Herbicide-induced experimental variegate prophyria in mice: tissue porphyrinogen accumulation and response to porphyrogenic drugs
J Krijt, P Stranska, P Maruna, M Vokurka, J Sanitrak
Canadian Journal of Physiology and Pharmacology 1997
Mapping of the variegate porphyria (VP) gene: Contradictory evidence for linkage between VP and microsatellite markers at chromosome 14q32
L Warnich, PN Meissner, RJ Hift, JH Louw, CJ Heerden, AE Retief
Human Genetics 1996
A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria
PN Meissner, TA Dailey, RJ Hift, M Ziman, AV Corrigall, AG Roberts, DM Meissner, RE Kirsch, HA Dailey
Nature Genetics 1996
Mapping of the variegate porphyria (VP) gene: contradictory evidence for linkage between VP and microsatellite markers at chromosome 14q32.
Warnich L, Meissner PN, Hift RJ, Louw JH, van Heerden CJ, Retief AE
Human Genetics 1996
Diseases of metabolism (porphyrias)
NA McCarroll
Analytical Chemistry 1995
Porphyrias: Clinical Evaluation and Interpretation of Laboratory Tests
A Tefferi, LA Solberg, RD Ellefson
Mayo Clinic Proceedings 1994
Acute Porphyrias: Diagnosis and Management
A Tefferi, JP Colgan, LA Solberg
Mayo Clinic Proceedings 1994

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