Biomaterial Database

Regulation of 5-aminolevulinate synthase in mouse erythroleukemic cells is different from that in liver. 1988

C J Elferink, and S Sassa, and B K May

Department of Pharmacology, Stanford University School of Medicine, California 94305.

We have measured the transcriptional gene activity of 5-aminolevulinate synthase, the first enzyme of the heme biosynthetic pathway, together with corresponding mRNA and protein levels in mouse erythroleukemic cells induced to differentiate with dimethyl sulfoxide. When the heme biosynthetic pathway was blocked by succinylacetone there was a large increase in both 5-aminolevulinate synthase activity and protein levels, and this was reversed by the addition of exogenous hemin. Transcriptional activity of the 5-aminolevulinate synthase gene and mRNA levels were both significantly increased during differentiation of cells by dimethyl sulfoxide but were not markedly altered by succinylacetone or hemin treatment. The results demonstrate that levels of 5-aminolevulinate synthase in mouse erythroleukemic cells are regulated by a significant post-transcriptional mechanism possibly at the translational level. Evidence is also presented for a less significant post-transcriptional control by heme of mRNA levels for 5-aminolevulinate synthase. These results indicate that the regulation of 5-aminolevulinate synthase in differentiating erythroid cells is complex but differs from that in liver cells where heme controls the level of 5-aminolevulinate synthase by acting primarily to inhibit gene transcription.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D004915	Leukemia, Erythroblastic, Acute	A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.	Di Guglielmo's Disease,Erythremic Myelosis,Erythroblastic Leukemia, Acute,Erythroleukemia,Leukemia, Myeloid, Acute, M6,Myeloid Leukemia, Acute, M6,Di Guglielmo Disease,Acute Erythroblastic Leukemia,Acute Erythroblastic Leukemias,Di Guglielmos Disease,Disease, Di Guglielmo,Disease, Di Guglielmo's,Erythremic Myeloses,Erythroblastic Leukemias, Acute,Erythroleukemias,Leukemia, Acute Erythroblastic,Leukemias, Acute Erythroblastic,Myeloses, Erythremic,Myelosis, Erythremic
D006427	Hemin	Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen.	Ferriprotoporphyrin,Hematin,Alkaline Hematin D-575,Chlorohemin,Ferrihaem,Ferriheme Chloride,Ferriprotoporphyrin IX,Ferriprotoporphyrin IX Chloride,Panhematin,Protohemin,Protohemin IX,Alkaline Hematin D 575,Chloride, Ferriheme,Chloride, Ferriprotoporphyrin IX,Hematin D-575, Alkaline
D006537	Heptanoates	Salts and esters of the 7-carbon saturated monocarboxylic acid heptanoic acid.	Enanthates
D000624	5-Aminolevulinate Synthetase	An enzyme of the transferase class that catalyzes condensation of the succinyl group from succinyl coenzyme A with glycine to form delta-aminolevulinate. It is a pyridoxyal phosphate protein and the reaction occurs in mitochondria as the first step of the heme biosynthetic pathway. The enzyme is a key regulatory enzyme in heme biosynthesis. In liver feedback is inhibited by heme. EC 2.3.1.37.	Aminolevulinic Acid Synthetase,delta-Aminolevulinate Synthase,5-Aminolevulinate Synthase,delta-Aminolevulinic Acid Synthetase,5 Aminolevulinate Synthase,5 Aminolevulinate Synthetase,Acid Synthetase, Aminolevulinic,Acid Synthetase, delta-Aminolevulinic,Synthase, 5-Aminolevulinate,Synthase, delta-Aminolevulinate,Synthetase, 5-Aminolevulinate,Synthetase, Aminolevulinic Acid,Synthetase, delta-Aminolevulinic Acid,delta Aminolevulinate Synthase,delta Aminolevulinic Acid Synthetase
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014158	Transcription, Genetic	The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.	Genetic Transcription
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus