{"id":"https://openalex.org/W2011040876","doi":"https://doi.org/10.1172/jci108895","title":"Study of factors causing excess protoporphyrin accumulation in cultured skin fibroblasts from patients with protoporphyria.","display_name":"Study of factors causing excess protoporphyrin accumulation in cultured skin fibroblasts from patients with protoporphyria.","publication_year":1977,"publication_date":"1977-12-01","ids":{"openalex":"https://openalex.org/W2011040876","doi":"https://doi.org/10.1172/jci108895","mag":"2011040876","pmid":"https://pubmed.ncbi.nlm.nih.gov/915001","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/372492"},"language":"en","primary_location":{"id":"doi:10.1172/jci108895","doi":"https://doi.org/10.1172/jci108895","is_oa":true,"landing_page_url":"https://doi.org/10.1172/jci108895","pdf_url":"http://www.jci.org/articles/view/108895/files/pdf","source":{"id":"https://openalex.org/S114430552","display_name":"Journal of Clinical Investigation","issn_l":"0021-9738","issn":["0021-9738","1558-8238"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320279","host_organization_name":"American Society for Clinical Investigation","host_organization_lineage":["https://openalex.org/P4310320279"],"host_organization_lineage_names":["American Society for Clinical Investigation"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Investigation","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"http://www.jci.org/articles/view/108895/files/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5108549221","display_name":"Joseph R. Bloomer","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"J R Bloomer","raw_affiliation_strings":["Departments of Medicine and Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicine and Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5015535660","display_name":"David A. Brenner","orcid":"https://orcid.org/0000-0003-2573-525X","observed_orcids":["https://orcid.org/0000-0003-2573-525X"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"D A Brenner","raw_affiliation_strings":["Departments of Medicine and Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicine and Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5111655287","display_name":"MauriceJ. Mahoney","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"M J Mahoney","raw_affiliation_strings":["Departments of Medicine and Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicine and Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510","institution_ids":["https://openalex.org/I32971472"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I32971472"],"apc_list":{"value":5200,"currency":"USD","value_usd":5200},"apc_paid":null,"fwci":1.2294,"has_fulltext":true,"cited_by_count":52,"citation_normalized_percentile":{"value":0.75566962,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":95},"biblio":{"volume":"60","issue":"6","first_page":"1354","last_page":"1361"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12441","display_name":"Porphyrin Metabolism and Disorders","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12441","display_name":"Porphyrin Metabolism and Disorders","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12068","display_name":"Neonatal Health and Biochemistry","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2735","display_name":"Pediatrics, Perinatology and Child Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11848","display_name":"Heme Oxygenase-1 and Carbon Monoxide","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/protoporphyria","display_name":"protoporphyria","score":0.9649999737739563},{"id":"https://openalex.org/keywords/protoporphyrin-accumulation","display_name":"protoporphyrin accumulation","score":0.996999979019165},{"id":"https://openalex.org/keywords/heme-biosynthesis","display_name":"heme biosynthesis","score":0.8019999861717224},{"id":"https://openalex.org/keywords/delta-aminolevulinic-acid-synthase","display_name":"delta-aminolevulinic acid synthase","score":0.9679999947547913},{"id":"https://openalex.org/keywords/dermal-fibroblasts","display_name":"dermal fibroblasts","score":0.8999999761581421},{"id":"https://openalex.org/keywords/iron-availability","display_name":"iron availability","score":0.6110000014305115},{"id":"https://openalex.org/keywords/5-aminolevulinic-acid","display_name":"5-aminolevulinic acid","score":0.8679999709129333},{"id":"https://openalex.org/keywords/glycine-incorporation","display_name":"glycine incorporation","score":0.5839999914169312}],"concepts":[{"id":"https://openalex.org/C2778417259","wikidata":"https://www.wikidata.org/wiki/Q619815","display_name":"Protoporphyrin","level":3,"score":0.9192308783531189},{"id":"https://openalex.org/C2776217839","wikidata":"https://www.wikidata.org/wiki/Q189621","display_name":"Heme","level":3,"score":0.8969736099243164},{"id":"https://openalex.org/C2777799353","wikidata":"https://www.wikidata.org/wiki/Q1759600","display_name":"Erythropoietic protoporphyria","level":4,"score":0.8645628094673157},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.6379423141479492},{"id":"https://openalex.org/C2781149050","wikidata":"https://www.wikidata.org/wiki/Q408712","display_name":"Ferrochelatase","level":4,"score":0.6279481053352356},{"id":"https://openalex.org/C2779671804","wikidata":"https://www.wikidata.org/wiki/Q619815","display_name":"Protoporphyrin IX","level":3,"score":0.6269230842590332},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5768925547599792},{"id":"https://openalex.org/C2777756961","wikidata":"https://www.wikidata.org/wiki/Q620730","display_name":"Glycine","level":3,"score":0.5459132194519043},{"id":"https://openalex.org/C2775832776","wikidata":"https://www.wikidata.org/wiki/Q65122087","display_name":"Ferrous","level":2,"score":0.4896843731403351},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.44957435131073},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.3755599856376648},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.28107750415802},{"id":"https://openalex.org/C2779480358","wikidata":"https://www.wikidata.org/wiki/Q422926","display_name":"Porphyrin","level":2,"score":0.2621764540672302},{"id":"https://openalex.org/C515207424","wikidata":"https://www.wikidata.org/wiki/Q8066","display_name":"Amino acid","level":2,"score":0.18809375166893005},{"id":"https://openalex.org/C2781323092","wikidata":"https://www.wikidata.org/wiki/Q1428072","display_name":"Photodynamic therapy","level":2,"score":0.06798931956291199},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D002250","descriptor_name":"Carbon Radioisotopes","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002478","descriptor_name":"Cells, Cultured","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002855","descriptor_name":"Chromatography, Thin Layer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005347","descriptor_name":"Fibroblasts","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007504","descriptor_name":"Iron Radioisotopes","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011164","descriptor_name":"Porphyrias","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011166","descriptor_name":"Porphyrins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011524","descriptor_name":"Protoporphyrins","qualifier_ui":"Q000032","qualifier_name":"analysis","is_major_topic":false},{"descriptor_ui":"D011524","descriptor_name":"Protoporphyrins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D012867","descriptor_name":"Skin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D013050","descriptor_name":"Spectrometry, Fluorescence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":5,"locations":[{"id":"doi:10.1172/jci108895","doi":"https://doi.org/10.1172/jci108895","is_oa":true,"landing_page_url":"https://doi.org/10.1172/jci108895","pdf_url":"http://www.jci.org/articles/view/108895/files/pdf","source":{"id":"https://openalex.org/S114430552","display_name":"Journal of Clinical Investigation","issn_l":"0021-9738","issn":["0021-9738","1558-8238"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320279","host_organization_name":"American Society for Clinical Investigation","host_organization_lineage":["https://openalex.org/P4310320279"],"host_organization_lineage_names":["American Society for Clinical Investigation"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Investigation","raw_type":"journal-article"},{"id":"pmh:oai:europepmc.org:1460492","doi":null,"is_oa":true,"landing_page_url":"http://europepmc.org/articles/PMC372492","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"","raw_type":"Text"},{"id":"pmh:oai:pubmedcentral.nih.gov:372492","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/372492","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"J Clin Invest","raw_type":"Text"},{"id":"pmid:915001","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/915001","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of clinical investigation","raw_type":"Journal Article"},{"id":"pmh:oai:CiteSeerX.psu:10.1.1.972.9545","doi":null,"is_oa":false,"landing_page_url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.972.9545","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"http://dm5migu4zj3pb.cloudfront.net/manuscripts/108000/108895/JCI77108895.pdf","raw_type":"text"}],"best_oa_location":{"id":"doi:10.1172/jci108895","doi":"https://doi.org/10.1172/jci108895","is_oa":true,"landing_page_url":"https://doi.org/10.1172/jci108895","pdf_url":"http://www.jci.org/articles/view/108895/files/pdf","source":{"id":"https://openalex.org/S114430552","display_name":"Journal of Clinical Investigation","issn_l":"0021-9738","issn":["0021-9738","1558-8238"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320279","host_organization_name":"American Society for Clinical Investigation","host_organization_lineage":["https://openalex.org/P4310320279"],"host_organization_lineage_names":["American Society for Clinical Investigation"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Investigation","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.766700029373169,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2125600575","display_name":"TISSUE CULTURE STUDIES OF INBORN METABOLIC ERRORS","funder_award_id":"5r01am012579-17","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"}],"funders":[{"id":"https://openalex.org/F4320306182","display_name":"March of Dimes Foundation","ror":"https://ror.org/04bd5p711"},{"id":"https://openalex.org/F4320308380","display_name":"Yale University","ror":"https://ror.org/03v76x132"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2011040876.pdf","grobid_xml":"https://content.openalex.org/works/W2011040876.grobid-xml"},"referenced_works_count":34,"referenced_works":["https://openalex.org/W105127645","https://openalex.org/W1513230411","https://openalex.org/W1604536885","https://openalex.org/W1748793784","https://openalex.org/W1773246693","https://openalex.org/W1775749144","https://openalex.org/W1935083736","https://openalex.org/W1967528101","https://openalex.org/W1998006032","https://openalex.org/W1999974950","https://openalex.org/W2006433745","https://openalex.org/W2015630137","https://openalex.org/W2022780552","https://openalex.org/W2035281747","https://openalex.org/W2039350746","https://openalex.org/W2043187843","https://openalex.org/W2051721380","https://openalex.org/W2082389512","https://openalex.org/W2088575848","https://openalex.org/W2089053268","https://openalex.org/W2093194763","https://openalex.org/W2108501083","https://openalex.org/W2138742728","https://openalex.org/W2155588768","https://openalex.org/W2166660261","https://openalex.org/W2309263909","https://openalex.org/W2315548061","https://openalex.org/W2320349909","https://openalex.org/W2334708450","https://openalex.org/W2397309176","https://openalex.org/W2410527906","https://openalex.org/W2414781255","https://openalex.org/W4256530802","https://openalex.org/W6742540841"],"related_works":["https://openalex.org/W7099480627","https://openalex.org/W2166660261","https://openalex.org/W1968060359","https://openalex.org/W1993497964","https://openalex.org/W7099565879","https://openalex.org/W2134286645","https://openalex.org/W1969936892","https://openalex.org/W1748793784","https://openalex.org/W2093194763","https://openalex.org/W1993432387"],"abstract_inverted_index":{"The":[0],"activity":[1,78],"of":[2,9,21,79,89,96,104,121,127,141,157,185,217,243,253],"heme":[3,55,62,90,122,186,234],"synthetase,":[4,83],"which":[5,67,92,228],"catalyzes":[6,93],"the":[7,77,84,94,105,118,125,139,144,155,169,195,215,241,251],"chelation":[8],"ferrous":[10],"iron":[11,190],"to":[12,14,50,70,116,194,199,232],"protoporphyrin":[13,131,197,224],"form":[15],"heme,":[16],"is":[17,59,68,100,229],"deficient":[18,233],"in":[19,31,72,102,114,134,143,151,175,203,214,226,246],"sonicates":[20],"skin":[22],"fibroblasts":[23,108,177],"cultured":[24,176],"from":[25,98,178],"patients":[26,179],"with":[27,35,112,180],"protoporphyria.":[28],"During":[29],"culture":[30],"Eagle's":[32],"medium":[33,145],"supplemented":[34],"fetal":[36],"calf":[37],"serum,":[38],"these":[39],"cells":[40],"do":[41],"not":[42,150,192],"accumulate":[43],"protoporphyrin,":[44],"however.":[45],"This":[46],"may":[47,237],"be":[48,238],"due":[49,230],"a":[51,64,200],"minimal":[52],"requirement":[53],"for":[54],"synthesis,":[56],"since":[57],"glycine":[58],"incorporated":[60],"into":[61],"at":[63],"low":[65],"rate":[66,242],"similar":[69,201],"that":[71,213,222],"normal":[73,101,152,204],"fibroblasts.":[74,106],"In":[75,124],"addition,":[76],"delta-aminolevulinic":[80],"acid":[81],"(ALA)":[82],"first":[85],"and":[86,205,249],"rate-limiting":[87,119],"enzyme":[88],"biosynthesis":[91],"formation":[95,245],"ALA":[97,113,142,158,244],"glycine,":[99],"lysates":[103],"Cultured":[107],"were":[109],"therefore":[110],"incubated":[111],"order":[115],"bypass":[117],"step":[120],"biosynthesis.":[123],"presence":[126,216],"25":[128],"muM":[129],"iron,":[130],"was":[132,159,171,191,209],"detected":[133],"protoporphyria":[135,206],"cell":[136],"lines":[137,165],"when":[138],"concentration":[140,156],"reached":[146],"50":[147,162],"muM,":[148,163],"but":[149],"lines.":[153],"As":[154],"increased":[160],"above":[161],"all":[164],"accumulated":[166,198],"protoporphyrin.":[167],"However,":[168],"amount":[170],"2-3":[172],"times":[173],"more":[174,211],"protoporphyria,":[181,227],"reflecting":[182],"their":[183],"deficiency":[184],"synthetase":[187,235],"activity.":[188],"When":[189],"added":[193],"medium,":[196],"degree":[202],"fibroblasts;":[207],"this":[208],"significantly":[210],"than":[212],"iron.":[218,254],"These":[219],"studies":[220],"indicate":[221],"excessive":[223],"accumulation":[225],"principally":[231],"activity,":[236],"modified":[239],"by":[240,250],"heme-producing":[247],"tissues,":[248],"availability":[252]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2019,"cited_by_count":1},{"year":2015,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}