同: 5-aminolevulinic acid synthetase

PrepTutorEJDIC

〈U〉〈C〉(…の)(量・額などの)不足,欠乏《+『of』(『in』)+『名』》 / 〈C〉不足分,不足量,不足額 / 〈C〉(精神・肉体などの)欠陥
Alabama
ああ,あわれ(悲しみ・後悔などを表す声)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 先天性および後天性鉄芽球性貧血の原因 causes of congenital and acquired sideroblastic anemias
2. 骨髄性プロトポルフィリン症 erythropoietic protoporphyria
3. ALA脱水酵素欠損性ポルフィリン症 ala dehydratase porphyria
4. 鉄のバランス調節 regulation of iron balance
5. 小児期の鉛中毒：臨床症状および診断 childhood lead poisoning clinical manifestations and diagnosis

English Journal

Molecular and functional analysis of the C-terminal region of human erythroid-specific 5-aminolevulinic synthase associated with X-linked dominant protoporphyria (XLDPP).

Ducamp S1, Schneider-Yin X, de Rooij F, Clayton J, Fratz EJ, Rudd A, Ostapowicz G, Varigos G, Lefebvre T, Deybach JC, Gouya L, Wilson P, Ferreira GC, Minder EI, Puy H.Author information 1AP-HP, Centre Franc¸ais des Porphyries, Hoˆ pital Louis Mourier, 178 rue des Renouillers, 92701 Colombes Cedex,France.AbstractFrameshift mutations in the last coding exon of the 5-aminolevulinate synthase (ALAS) 2 gene were described to activate the enzyme causing increased levels of zinc- and metal-free protoporphyrin in patients with X-linked dominant protoporphyria (XLDPP). Only two such so-called gain-of-function mutations have been reported since the description of XLDPP in 2008. In this study of four newly identified XLDPP families, we identified two novel ALAS2 gene mutations, a nonsense p.Q548X and a frameshift c.1651-1677del26bp, along with a known mutation (delAGTG) found in two unrelated families. Of relevance, a de novo somatic and germinal mosaicism was present in a delAGTG family. Such a phenomenon may explain the high proportion of this mutation in XLDPP worldwide. Enhancements of over 3- and 14-fold in the catalytic rate and specificity constant of purified recombinant XLDPP variants in relation to those of wild-type ALAS2 confirmed the gain of function ascribed to these enzymes. The fact that both p.Q548X and c.1651-1677del26bp are located in close proximity and upstream from the two previously described mutations led us to propose the presence of a large gain-of-function domain within the C-terminus of ALAS2. To test this hypothesis, we generated four additional nonsense mutants (p.A539X, p.G544X, p.G576X and p.V583X) surrounding the human XLDPP mutations and defined an ALAS2 gain-of-function domain with a minimal size of 33 amino acids. The identification of this gain-of-function domain provides important information on the enzymatic activity of ALAS2, which was proposed to be constitutively inhibited, either directly or indirectly, through its own C-terminus.
Human molecular genetics.Hum Mol Genet.2013 Apr 1;22(7):1280-8. doi: 10.1093/hmg/dds531. Epub 2012 Dec 20.
Frameshift mutations in the last coding exon of the 5-aminolevulinate synthase (ALAS) 2 gene were described to activate the enzyme causing increased levels of zinc- and metal-free protoporphyrin in patients with X-linked dominant protoporphyria (XLDPP). Only two such so-called gain-of-function mutat
PMID 23263862

PGC-1alpha negatively regulates hepatic FGF21 expression by modulating the heme/Rev-Erb(alpha) axis.

Estall JL1, Ruas JL, Choi CS, Laznik D, Badman M, Maratos-Flier E, Shulman GI, Spiegelman BM.Author information 1Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.AbstractFGF21 is a hormone produced in liver and fat that dramatically improves peripheral insulin sensitivity and lipid metabolism. We show here that obese mice with genetically reduced levels of a key hepatic transcriptional coactivator, PGC-1alpha, have improved whole-body insulin sensitivity with increased levels of hepatic and circulating FGF21. Gain- and loss-of-function studies in primary mouse hepatocytes show that hepatic FGF21 levels are regulated by the expression of PGC-1alpha. Importantly, PGC-1alpha-mediated reduction of FGF21 expression is dependent on Rev-Erbalpha and the expression of ALAS-1. ALAS-1 is a PGC-1alpha target gene and the rate-limiting enzyme in the synthesis of heme, a ligand for Rev-Erbalpha. Modulation of intracellular heme levels mimics the effect of PGC-1alpha on FGF21 expression, and inhibition of heme biosynthesis completely abrogates the down-regulation of FGF21 in response to PGC-1alpha. Thus, PGC-1alpha can impact hepatic and systemic metabolism by regulating the levels of a nuclear receptor ligand.
Proceedings of the National Academy of Sciences of the United States of America.Proc Natl Acad Sci U S A.2009 Dec 29;106(52):22510-5. doi: 10.1073/pnas.0912533106. Epub 2009 Dec 14.
FGF21 is a hormone produced in liver and fat that dramatically improves peripheral insulin sensitivity and lipid metabolism. We show here that obese mice with genetically reduced levels of a key hepatic transcriptional coactivator, PGC-1alpha, have improved whole-body insulin sensitivity with increa
PMID 20018698

Erythropoietic protoporphyria.

Lecha M1, Puy H, Deybach JC.Author information 1Department of Dermatology, Hospital Clinic, University of Barcelona, Barcelona, Spain. 4908mlc@comb.esAbstractErythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. EPP has been reported worldwide, with prevalence between 1:75,000 and 1:200,000. It usually manifests in early infancy upon the first sun exposures. EPP is characterised by cutaneous manifestations of acute painful photosensitivity with erythema and oedema, sometimes with petechiae, together with stinging and burning sensations upon exposure to sunlight, without blisters. These episodes have a variable severity depending on the exposure duration and may result in chronic permanent lesions on exposed skin. As protoporphyrin is a lipophilic molecule that is excreted by the liver, EPP patients are at risk of cholelithiasis with obstructive episodes, and chronic liver disease that might evolve to rapid acute liver failure. In most patients, EPP results from a partial deficiency of the last enzyme of the haem biosynthetic pathway, ferrochelatase, EC 4.99.1.1/FECH (encoded by the FECH gene). EPP appears to be inherited as an autosomal dominant disease, the clinical expression of which is modulated by the presence of the hypomorphic FECH IVS3-48C allele trans, but recessive inheritance with two mutated FECH alleles has also been described. In about 2% of patients, overt disease was recently shown to be caused by gain-of-function mutations in the erythroid-specific aminolevulinic acid synthase 2 (ALAS2/ALAS, EC 2.3.1.27) gene and named X-linked dominant protoporphyria. Diagnosis is established by finding increased levels of protoporphyrin in plasma and red blood cells, and detection of a plasma fluorescence peak at 634 nm. Investigations for hepatic involvement, ferrochelatase activity level, genetic analysis (FECH mutations, presence of the hypomorphic FECH IVS3-48C allele trans and ALAS2 mutations) and family studies are advisable. Differential diagnosis includes phototoxic drug reactions, hydroa vacciniforme, solar urticaria, contact dermatitis, angio-oedema and, in some cases, other types of porphyria. Management includes avoidance of exposure to light, reduction of protoporphyrin levels and prevention of progression of possible liver disease to liver failure. As the major risk in EPP patients is liver disease, a regular follow-up of hepatic involvement is essential. Sequential hepatic and bone marrow transplantation should be considered as a suitable treatment for most severe cases of EPP with hepatic involvement. EPP is a lifelong disorder whose prognosis depends on the evolution of the hepatic disease. However, photosensitivity may have a significant impact on quality of life of EPP patients.
Orphanet journal of rare diseases.Orphanet J Rare Dis.2009 Sep 10;4:19. doi: 10.1186/1750-1172-4-19.
Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. EPP has been reported worldwide, with prevalence between 1:75,000 and 1:200
PMID 19744342

Japanese Journal

Heme as a Magnificent Molecule with Multiple Missions: Heme Determines Its Own Fate and Governs Cellular Homeostasis

Furuyama Kazumichi,Kaneko Kiriko,Vargas V. Patrick D.
The Tohoku Journal of Experimental Medicine 213(1), 1-16, 2007
… For example, protein synthesis is inhibited in erythroid cells under heme deficiency, as the consequence of the activation of heme-regulated inhibitor (HRI). … Heme reduces heme synthesis by suppressing the expression of non-specific 5-aminolevulinate synthase (ALAS1) and stimulates heme breakdown by inducing heme oxygenase (HO)-1 expression. … ALAS1 and HO-1 are the rate limiting enzymes in heme biosynthesis and catabolism, respectively. …
NAID 130004822089

ピリドキシン内服が著効した乳児鉄芽球性貧血

工藤寿子,伊藤雅文,堀部敬三,岩瀬勝彦,小島勢二
臨床血液 40(8), 667-672, 1999-08-30
症例は8カ月男児。顔色不良を指摘され，入院。入院時検査所見は赤血球数156×104/μl, Hb 3.5 g/dl, 平均赤血球容積66 flと高度な小球性低色素性貧血を認めたが，網状赤血球は0.5 ‰と低く，血清鉄は433 μg/dlで膵外分泌不全は認めなかった。骨髄所見は赤芽球の過形成がみられ，環状鉄芽球を18%に認めた。電顕所見では赤芽球のミトコンドリア内に鉄顆粒の沈着を認めた。以上より鉄芽 …
NAID 10006175115

Auger Depth Profiles of a GaAs/AlAs Superlattice Structure Obtained with O^+_2 and Ar^+ Ion Sputtering

LEE Hyung-Ik,MITSUHASHI Riichiro,INOUE Masahiko,SHIMIZU Ryuichi,HOFMANN Siegfried
Japanese journal of applied physics. Pt. 2, Letters 34(8A), L1010-L1012, 1995-08-01
… This technique was applied to depth profiling of a GaAs/AlAs superlattice by monitoring the Auger peak-to-background ratio of the following high-energy peaks; … Results show the deficiency of As atoms and the formation of Al oxides at the surface of O^+_2 -sputtered AlAs layers. …
NAID 110003922957