当前位置： SCI文献检索 > JOURNAL OF INHERITED METABOLIC DISEASE期刊下所有文献 > Molecular insights into the pathogenicity of variants associated with the aromatic amino acid decarboxylase deficiency.

Molecular insights into the pathogenicity of variants associated with the aromatic amino acid decarboxylase deficiency.

Abstract：

:Dopa decarboxylase (DDC or AADC) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the decarboxylation of L-aromatic amino acids into the corresponding aromatic amines. AADC deficiency is an inborn error of neurotransmitters biosynthesis with an autosomal recessive inheritance. About 30 pathogenic mutations have been identified, but the enzymatic phenotypes causing AADC deficiency are unknown, and the therapeutic management is challenging. Here, we report biochemical and bioinformatic analyses of the human wild-type DDC and the pathogenic variants G102S, F309L, S147R and A275T whose mutations concern amino acid residues at or near the active site. We found that the mutations cause, even if to different extents, a decreased PLP binding affinity (in the range 1.4-170-fold), an altered state of the bound coenzyme and of its microenvironment, and a reduced catalytic efficiency (in the range 17-930-fold). Moreover, as compared to wild-type, the external aldimines formed by the variants with L-aromatic amino acids exhibit different spectroscopic features, do not protect against limited proteolysis, and lead to the formation, in addition to aromatic amines, of cyclic-substrate adducts. This suggests that these external Schiff bases are not properly oriented and anchored, i.e., in a conformation not completely productive for decarboxylation. The external aldimines that the variants form with D-Dopa also appear not to be correctly located at their active site, as suggested by the rate constants of PLP-L-Dopa adduct production higher than that of the wild-type. The possible therapeutic implications of the data are discussed in the light of the molecular defects of the pathogenic variants.

journal_name

J Inherit Metab Dis

journal_title

Journal of inherited metabolic disease

authors

Montioli R,Cellini B,Borri Voltattorni C

doi

10.1007/s10545-011-9340-6

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

1213-24

issue

6

eissn

0141-8955

issn

1573-2665

journal_volume

34

pub_type

杂志文章

相关文献

JOURNAL OF INHERITED METABOLIC DISEASE文献大全
  • Mutation analysis in the iduronate-2-sulphatase gene in 43 Japanese patients with mucopolysaccharidosis type II (Hunter disease).

    abstract：:Our series of studies on Hunter disease in Japanese patients showed allelic heterogeneity of IDS gene mutations, genotype/phenotype correlation and racial differences in distribution of mutations. Twenty-five different small mutations have been characterized. Small mutations in the Japanese population are widely distr...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1023/a:1005363414792

    authors： Isogai K,Sukegawa K,Tomatsu S,Fukao T,Song XQ,Yamada Y,Fukuda S,Orii T,Kondo N

    更新日期：1998-02-01 00:00:00

  • The longest-surviving patient with classical maple syrup urine disease.

    abstract：:The clinical problems, dietary management and biochemical monitoring over a 40-year period of the longest-surviving patient with maple syrup urine disease are described. Her case illustrates that a good outcome can be obtained with early diagnosis and institution of a diet restricted in branched-chain amino acids. Cha...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-006-0204-4

    authors： le Roux C,Murphy E,Lilburn M,Lee PJ

    更新日期：2006-02-01 00:00:00

  • Menkes disease: underlying genetic defect and new diagnostic possibilities.

    abstract：:Cloning of the gene defective in the X-linked neurodegenerative disorder Menkes disease led to a cascade of new findings. Besides giving a better understanding of the intracellular copper homeostasis, these findings had important consequences from a clinical point of view. Today the underlying genetic defect has been ...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章,评审

    doi：10.1023/a:1005479307906

    authors： Tümer Z,Horn N

    更新日期：1998-08-01 00:00:00

  • Congenital disorders of glycosylation (CDG): update and new developments.

    abstract：:After a brief overview on CDG, this workshop concentrated on the experience with (mostly) known CDG in a European country (the Czech Republic) and on the Australasian experience, on recent developments regarding congenital muscular dystrophies due to O-mannoslyglycan assembly defects, and on new presentations of CDG. ...

    journal_title：Journal of inherited metabolic disease

    pub_type： 共识发展会议,杂志文章,评审

    doi：10.1023/b:boli.0000031221.44647.9e

    authors： Jaeken J

    更新日期：2004-01-01 00:00:00

  • Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency: a sibling comparison study.

    abstract：OBJECTIVE:Acyl-CoA oxidase (ACOX1) deficiency is a rare disorder of peroxisomal very-long chain fatty acid oxidation. No reports detailing attempted treatment, longitudinal imaging, or neuropathology exist. We describe the natural history of clinical symptoms and brain imaging in two siblings with ACOX1 deficiency, inc...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-014-9698-3

    authors： Wang RY,Monuki ES,Powers J,Schwartz PH,Watkins PA,Shi Y,Moser A,Shrier DA,Waterham HR,Nugent DJ,Abdenur JE

    更新日期：2014-09-01 00:00:00

  • Tract-based evaluation of white matter damage in individuals with early-treated phenylketonuria.

    abstract：:Previous research has documented white matter abnormalities in the brains of individuals with early-treated phenylketonuria (ETPKU). The majority of these past studies have relied on a region-based approach which focused on a limited number of spatially-defined regions within the brain. In the present study, we used d...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-013-9650-y

    authors： Peng H,Peck D,White DA,Christ SE

    更新日期：2014-03-01 00:00:00

  • Lyso-globotriaosylsphingosine (lyso-Gb3) levels in neonates and adults with the Fabry disease later-onset GLA IVS4+919G>A mutation.

    abstract：:Lyso-globotriaosylsphingosine (lyso-Gb3) is a useful biomarker in the diagnosis and monitoring of treatment for Fabry disease. However, it is unclear whether lyso-Gb3 is elevated in patients with later-onset Fabry disease. Thus, we measured lyso-Gb3 levels from dried blood spots (DBS) from male newborns with the Fabry...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-012-9547-1

    authors： Chien YH,Bodamer OA,Chiang SC,Mascher H,Hung C,Hwu WL

    更新日期：2013-09-01 00:00:00

  • Transaldolase haploinsufficiency in subjects with acetaminophen-induced liver failure.

    abstract：:Transaldolase (TAL) is an enzyme in the pentose phosphate pathway (PPP) that generates NADPH for protection against oxidative stress. While deficiency of other PPP enzymes, such as transketolase (TKT), are incompatible with mammalian cell survival, mice lacking TAL are viable and develop progressive liver disease attr...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1002/jimd.12197

    authors： Oaks Z,Jimah J,Grossman CC,Beckford M,Kelly R,Banerjee S,Niland B,Miklossy G,Kuloglu Z,Kansu A,Lee W,Szonyi L,Banki K,Perl A

    更新日期：2020-05-01 00:00:00

  • Analysis of synaptic proteins in the cerebrospinal fluid as a new tool in the study of inborn errors of neurotransmission.

    abstract：:In a few rare diseases, specialised studies in cerebrospinal fluid (CSF) are required to identify the underlying metabolic disorder. We aimed to explore the possibility of detecting key synaptic proteins in the CSF, in particular dopaminergic and gabaergic, as new procedures that could be useful for both pathophysiolo...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-010-9256-6

    authors： Duarte ST,Ortez C,Pérez A,Artuch R,García-Cazorla A

    更新日期：2011-04-01 00:00:00

  • D-2-Hydroxyglutaric aciduria with absence of corpus callosum and neonatal intracranial haemorrhage.

    abstract：:We report D-2-hydroxyglutaric aciduria in a neonate with intracranial haemorrhage and absence of the corpus callosum. D-2-hydroxyglutaric acid was confirmed by specific chiral derivatization gas chromatography-mass spectrometry. Absence of the corpus callosum and spontaneous neonatal intracranial haemorrhage should ra...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1023/a:1024000202364

    authors： Wang X,Jakobs C,Bawle EV

    更新日期：2003-01-01 00:00:00

  • The effect of L-alanine therapy in a patient with adult onset glycogen storage disease type II.

    abstract：:Adult-onset glycogen storage disease type II (GSD II) (McKusick 232300) is a progressive disabling myopathy. At present there is no treatment of proven clinical efficacy. Enzyme replacement therapy may in the future provide benefit but it will be costly and is not yet freely available. L-Alanine, a simple and relative...

    journal_title：Journal of inherited metabolic disease

    pub_type： 临床试验,杂志文章

    doi：10.1007/s10545-006-0238-7

    authors： Mundy HR,Williams JE,Cousins AJ,Lee PJ

    更新日期：2006-02-01 00:00:00

  • The effects of early and late bone marrow transplantation in siblings with alpha-mannosidosis. Is early haematopoietic cell transplantation the preferred treatment option?

    abstract：:This article documents both the neurological and physical outcomes of the first published set of siblings undergoing transplantation at differing ages for α-mannosidosis. The older brother, the index case, was diagnosed at the age of 3 years and underwent transplantation at 13 years for the treatment of increasing som...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-009-9035-4

    authors： Broomfield AA,Chakrapani A,Wraith JE

    更新日期：2010-12-01 00:00:00

  • Regulatory environment for novel therapeutic development in mitochondrial diseases.

    abstract：:At present, there is just one approved therapy for patients with mitochondrial diseases in Europe, another in Japan, and none in the United States. These facts reveal an important and significant unmet need for approved therapies for these debilitating and often fatal disorders. To fill this need, it is critical for c...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章,评审

    doi：10.1002/jimd.12353

    authors： Hirano M,Berardo A,Barca E,Emmanuele V,Quinzii C,Simpson CV,Engelstad K,Rosales XQ,Thompson JLP

    更新日期：2020-12-24 00:00:00

  • A new variant of glycogen storage disease type 1: probably due to a defect in the glucose-6-phosphate transport system.

    abstract：:A new variant of glycogen storage disease (GSD) Type 1, with clinical symptoms and laboratory findings consistent with those of glucose-6-phosphatase (G6Pase) deficiency, is described. Assay of G6Pase in liver from the patient immediately after biopsy by the method of Nordlie and Arion gave low activity (0.8 mumol/min...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/BF01801717

    authors： Igarashi Y,Otomo H,Narisawa K,Tada K

    更新日期：1980-01-01 00:00:00

  • Angiogenesis in alkaptonuria.

    abstract：:Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of AKU treatment is palliative and little is known about its physiopathology. Neovascularization is involved in the pathogenesis of systemic inflammatory rheumatic diseases, a family of related disorders that includes AKU. Her...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-016-9976-3

    authors： Millucci L,Bernardini G,Marzocchi B,Braconi D,Geminiani M,Gambassi S,Laschi M,Frediani B,Galvagni F,Orlandini M,Santucci A

    更新日期：2016-11-01 00:00:00

  • Clinical and molecular heterogeneity of cytochrome c oxidase deficiency in the newborn.

    abstract：:We report 8 cases of severe cytochrome c oxidase deficiency with onset in the neonatal period. Clinical symptoms were heterogeneous: antenatal cerebral malformations, neurological distress with ketoacidosis, severe myopathy, or isolated respiratory control failure. Lactic acid was elevated in blood and/or CSF in 7 cas...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/BF01799256

    authors： Lombes A,Romero NB,Touati G,Frachon P,Cheval MA,Giraud M,Simon D,Ogier de Baulny H

    更新日期：1996-01-01 00:00:00

  • Methionine adenosyltransferase (MAT) I/III deficiency with concurrent hyperhomocysteinaemia: two novel cases.

    abstract：:This study reports three novel mutations of the methionine adenosyltransferase (MAT) lA gene and confirms that hyperhomocysteinaemia may be a characteristic finding in MAT I/III deficiency. Thus, MAT I/III deficiency is important in the differential diagnoses of hyperhomocysteinaemia, which may lead to clinical compli...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-005-4497-5

    authors： Linnebank M,Lagler F,Muntau AC,Röschinger W,Olgemöller B,Fowler B,Koch HG

    更新日期：2005-01-01 00:00:00

  • Prenatal diagnosis and prevention of inherited abnormalities of collagen.

    abstract：:There is now strong evidence for the implication of collagen alpha 1(I), alpha 2(I) and alpha 1(III) mutations in many forms of osteogenesis imperfecta and inherited arterial aneurysms (Ehlers Danlos syndrome type IV). A sizeable proportion of these disorders have detectable abnormalities by conventional protein chemi...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章,评审

    doi：10.1007/BF01799292

    authors： Pope FM,Daw SC,Narcisi P,Richards AR,Nicholls AC

    更新日期：1989-01-01 00:00:00

  • Normal biochemical analysis of the oxidative phosphorylation (OXPHOS) system in a child with POLG mutations: a cautionary note.

    abstract：:We report a 5-year-old child carrying polymerase gamma (POLG1) mutations, but strikingly normal oxidative phosphorylation analysis in muscle, fibroblasts and liver. Mutations in POLG1 have so far been described in children with severe combined oxidative phosphorylation (OXPHOS) deficiencies and with the classical Alpe...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-008-0871-4

    authors： de Vries MC,Rodenburg RJ,Morava E,Lammens M,van den Heuvel LP,Korenke GC,Smeitink JA

    更新日期：2008-12-01 00:00:00

  • Neurocognitive profiles in MSUD school-age patients.

    abstract：:Maple syrup urine disease (MSUD), an inborn error of amino acids catabolism is characterized by accumulation of branched chain amino acids (BCAAs) leucine, isoleucine, valine and their corresponding alpha-ketoacids. Impact on the cognitive development has been reported historically, with developmental delays of varyin...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s10545-017-0033-7

    authors： Bouchereau J,Leduc-Leballeur J,Pichard S,Imbard A,Benoist JF,Abi Warde MT,Arnoux JB,Barbier V,Brassier A,Broué P,Cano A,Chabrol B,Damon G,Gay C,Guillain I,Habarou F,Lamireau D,Ottolenghi C,Paermentier L,Sabourdy F,

    更新日期：2017-05-01 00:00:00

  • Comparison of ornithine metabolism in hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome, lysinuric protein intolerance and gyrate atrophy fibroblasts.

    abstract：:We measured L-ornithine oxidation in cultured skin fibroblasts from seven patients with hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome (McKusick 23897), and compared it with oxidation by ornithine aminotransferase deficient gyrate atrophy (McKusick 25887) cells and lysinuric protein intolerance (M...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/BF01805528

    authors： Botschner J,Smith DW,Simell O,Scriver CR

    更新日期：1989-01-01 00:00:00

  • Therapy through chaperones: sense or antisense? Cystic fibrosis as a model disease.

    abstract：:Massive production and accumulation of a single abnormal protein may constitute a major toxic burden for the cell and even compromise the organism's long-term viability. Consequently, adaptation and survival have forced evolution to create 'quality control' mechanisms that detect, monitor, and often degrade such abnor...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章,评审

    doi：10.1007/s10545-006-0251-x

    authors： Amaral MD

    更新日期：2006-04-01 00:00:00

  • Pitfalls in diagnosing mitochondrial neurogastrointestinal encephalomyopathy.

    abstract：:Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by mutations in the gene encoding thymidine phosphorylase and is characterized by external ophthalmoparesis, gastrointestinal dysmotility, leukoencephalopathy, and neuropathy. The availability of new therapeutic opt...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-011-9332-6

    authors： Filosto M,Scarpelli M,Tonin P,Testi S,Cotelli MS,Rossi M,Salvi A,Grottolo A,Vielmi V,Todeschini A,Fabrizi GM,Padovani A,Tomelleri G

    更新日期：2011-12-01 00:00:00

  • Assessment of bone dysplasia by micro-CT and glycosaminoglycan levels in mouse models for mucopolysaccharidosis type I, IIIA, IVA, and VII.

    abstract：:Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases caused by mutations in lysosomal enzymes involved in degradation of glycosaminoglycans (GAGs). Patients with MPS grow poorly and become physically disabled due to systemic bone disease. While many of the major skeletal effects in mouse models for MP...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-012-9522-x

    authors： Rowan DJ,Tomatsu S,Grubb JH,Montaño AM,Sly WS

    更新日期：2013-03-01 00:00:00

  • Mild hyperphenylalaninemia: to treat or not to treat.

    abstract：:One of the issues to be resolved in phenylketonuria is whether patients with mild hyperphenylalaninemia need treatment, or in other words, in what patients treatment needs to be started. Do patients need treatment when phenylalanine concentrations in blood are >360 μmol/L or >600 μmol/L? This paper reviews the literat...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章,评审

    doi：10.1007/s10545-011-9283-y

    authors： van Spronsen FJ

    更新日期：2011-06-01 00:00:00

  • ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies.

    abstract：INTRODUCTION:Alpha-1,3-glucosyltransferase congenital disorder of glycosylation (ALG6-CDG) is a congenital disorder of glycosylation. The original patients were described with hypotonia, developmental disability, epilepsy, and increased bleeding tendency. METHODS:Based on Euroglycan database registration, we approache...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/s10545-016-9945-x

    authors： Morava E,Tiemes V,Thiel C,Seta N,de Lonlay P,de Klerk H,Mulder M,Rubio-Gozalbo E,Visser G,van Hasselt P,Horovitz DDG,de Souza CFM,Schwartz IVD,Green A,Al-Owain M,Uziel G,Sigaudy S,Chabrol B,van Spronsen FJ,Steinert

    更新日期：2016-09-01 00:00:00

  • Assessment of homocysteine status.

    abstract：:Plasma total homocysteine (tHcy) determination is used in the diagnosis of homocystinuria, in cobalamin and folate deficiency and in cardiovascular risk assessment. However, determination of tHcy includes many pitfalls which complicate the assessment of homocysteine status. In the present article, we review basic know...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章,评审

    doi：10.1023/a:1005321225893

    authors： Refsum H,Fiskerstrand T,Guttormsen AB,Ueland PM

    更新日期：1997-06-01 00:00:00

  • Fertility and pregnancy in women affected by glycogen storage disease type I, results of a multicenter Italian study.

    abstract：BACKGROUND:Life expectancy of patients with glycogen storage disease (GSD) type I has improved considerably, opening new problems correlated with adult age. In females polycystic ovaries (PCOs) has been described as frequently associated with the disease, however successful pregnancies have been reported. Whether or no...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s10545-012-9490-1

    authors： Sechi A,Deroma L,Lapolla A,Paci S,Melis D,Burlina A,Carubbi F,Rigoldi M,Di Rocco M

    更新日期：2013-01-01 00:00:00

  • Multiple sulphatase deficiency in homozygotic twins.

    abstract：:Multiple sulphatase deficiency was studied in 3 siblings--one pair of monozygotic twins and their sister. The children's psychomotor development was arrested at the age of 18 to 24 months, and the hypotonic syndrome combined with signs of spasticity appeared. There was marked hepatosplenomegaly, conspicuously dry scal...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章

    doi：10.1007/BF01805620

    authors： Nevsímalová S,Elleder M,Smíd F,Zemánková M

    更新日期：1984-01-01 00:00:00

  • Propofol administration in patients with methylmalonic acidemia and intracellular cobalamin metabolism disorders: a review of theoretical concerns and clinical experiences in 28 patients.

    abstract：BACKGROUND:Methylmalonic acidemia and intracellular cobalamin metabolism disorders represent a heterogeneous group of inborn errors of metabolism. Most patients will require diagnostic and/or therapeutic procedures frequently requiring sedation or anesthetic management due to neurological and neurocognitive impairments...

    journal_title：Journal of inherited metabolic disease

    pub_type： 杂志文章,评审

    doi：10.1007/s10545-015-9816-x

    authors： Ktena YP,Ramstad T,Baker EH,Sloan JL,Mannes AJ,Manoli I,Venditti CP

    更新日期：2015-09-01 00:00:00