A regulatory role for porphobilinogen deaminase (PBGD) in δ-aminolaevulinic acid (δ-ALA)-induced photosensitization?
Open accessAbstract
As an initial approach to optimize delta-aminolaevulinic acid (delta-ALA)-induced photosensitization of tumours, we examined the response of three enzymes of the haem biosynthetic pathway: delta-ALA dehydratase, porphobilinogen deaminase (PBGD) and ferrochelatase. Only PBGD activity displayed a time- and dose-related increase in tumours after intravenous administration of 300 mg kg(-1) delta-ALA. The time course for porphyrin fluorescence changes, reflecting increased production of the penultimate porphyrin, protoporphyrin IX (PPIX), showed a similar pattern to PBGD. This apparent correlation between PBGD activity and porphyrin fluorescence was also observed in four cultured tumour cell lines exposed to 0.1-2.0 mM delta-ALA in vitro. The increase in PBGD activity and PPIX fluorescence was prevented by the protein synthesis inhibitor cycloheximide. As the apparent Km for PBGD was similar before and after delta-ALA, the increase in PBGD activity was attributed to induction of enzyme de novo. These observations of an associated response of PBGD and PPIX imply that PBGD may be a rate-limiting determinant for the efficacy of delta-ALA-induced photosensitization when used in photodynamic therapy.
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Although the uptake of ALA is non-selective, accumulation of PpIX in tumor cells may occur selectively because of alterations in enzymatic activity in the heme synthesis pathway.
“Although the uptake of ALA is non-selective, accumulation of PpIX in tumor cells may occur selectively because of alterations in enzymatic activity in the heme synthesis pathway.”
From Photodynamic Therapy for Non-Melanoma Skin Cancers (2016) · cites this paper as [9]
The accumulation of PpIX in neoplastic tissue is further supplemented by decreased activity of ferrochelatase (FC), which converts PpIX to heme.
“The accumulation of PpIX in neoplastic tissue is further supplemented by decreased activity of ferrochelatase (FC), which converts PpIX to heme [9,10].”
From Photodynamic Therapy for Non-Melanoma Skin Cancers (2016) · cites this paper as [9]
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Chapter 8 Basic principles of 5-aminolevulinic acid-based photodynamic therapy
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Self-citationPorphyrin Synthesis from 5-Aminolevulinic Acid in Patients with Glioma
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Forward Genetics in Apicomplexa Biology: The Host Side of the Story
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Exogenously Induced Endogenous Photosensitizers
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Gastric Cancer (Primary Tumor, Peritoneal Dissemination)
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- Authors
- Gibson, S., Cupriks, D., Havens, J., Nguyen, M., & Hilf, R.
- Affiliations
- University of Rochester Medicine (US)
- Venue
- British Journal of Cancer
- Published
- 1998-01
- Volume
- 77
- Issue
- 2
- Pages
- 235-242
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2151216
- OpenAlex
- W2026741498
- Cited by
- 78
- References
- 35
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 1 · 2013: 2 · 2012: 3
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- British Journal of Cancer (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Rochester
- National Institutes of Health (5r01ca036856-16, 5p30ca011198-28)
- National Cancer Institute (CA1 1198, CA 36856)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Physical Sciences › Materials Science › Materials Chemistry › Porphyrin and Phthalocyanine Chemistry
- Keywords
- porphobilinogen deaminase, 5-aminolevulinic acid, photosensitization, photodynamic therapy, heme biosynthesis, protoporphyrin IX, porphyrin fluorescence, enzyme induction, cancer cell lines, cycloheximide, ferrochelatase
- MeSH terms
- Aminolevulinic Acid, Porphobilinogen Synthase, Animals, Cycloheximide, Female, Ferrochelatase, Humans, Mice, Nude, Photochemotherapy, Hydroxymethylbilane Synthase, Porphyrins, Spectrometry, Fluorescence, Tumor Cells, Cultured, Photosensitizing Agents, Mice, Rats
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