当前位置： SCI文献检索 > MOLECULAR GENETICS AND METABOLISM期刊下所有文献 > Systems biology study of mucopolysaccharidosis using a human metabolic reconstruction network.

Systems biology study of mucopolysaccharidosis using a human metabolic reconstruction network.

Abstract：

:Mucopolysaccharidosis (MPS) is a group of lysosomal storage diseases (LSD), characterized by the deficiency of a lysosomal enzyme responsible for the degradation of glycosaminoglycans (GAG). This deficiency leads to the lysosomal accumulation of partially degraded GAG. Nevertheless, deficiency of a single lysosomal enzyme has been associated with impairment in other cell mechanism, such as apoptosis and redox balance. Although GAG analysis represents the main biomarker for MPS diagnosis, it has several limitations that can lead to a misdiagnosis, whereby the identification of new biomarkers represents an important issue for MPS. In this study, we used a system biology approach, through the use of a genome-scale human metabolic reconstruction to understand the effect of metabolism alterations in cell homeostasis and to identify potential new biomarkers in MPS. In-silico MPS models were generated by silencing of MPS-related enzymes, and were analyzed through a flux balance and variability analysis. We found that MPS models used approximately 2286 reactions to satisfy the objective function. Impaired reactions were mainly involved in cellular respiration, mitochondrial process, amino acid and lipid metabolism, and ion exchange. Metabolic changes were similar for MPS I and II, and MPS III A to C; while the remaining MPS showed unique metabolic profiles. Eight and thirteen potential high-confidence biomarkers were identified for MPS IVB and VII, respectively, which were associated with the secondary pathologic process of LSD. In vivo evaluation of predicted intermediate confidence biomarkers (β-hexosaminidase and β-glucoronidase) for MPS IVA and VI correlated with the in-silico prediction. These results show the potential of a computational human metabolic reconstruction to understand the molecular mechanisms this group of diseases, which can be used to identify new biomarkers for MPS.

journal_name

Mol Genet Metab

journal_title

Molecular genetics and metabolism

authors

Salazar DA,Rodríguez-López A,Herreño A,Barbosa H,Herrera J,Ardila A,Barreto GE,González J,Alméciga-Díaz CJ

doi

10.1016/j.ymgme.2015.08.001

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

129-39

issue

2

eissn

1096-7192

issn

1096-7206

pii

S1096-7192(15)30036-6

journal_volume

117

pub_type

杂志文章

相关文献

MOLECULAR GENETICS AND METABOLISM文献大全
  • Impact of premature birth and critical illness on neonatal range of plasma amino acid concentrations determined by LC-MS/MS.

    abstract：BACKGROUND:The number of newborns and the number of disorders detected by large-scale screening programs has increased dramatically in the last decade. Newborn screening is a multi-step process requiring confirmatory testing to establish and refine a diagnosis. Whereas screening cutoffs are established to detect all ca...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2011.08.020

    authors： Oladipo OO,Weindel AL,Saunders AN,Dietzen DJ

    更新日期：2011-12-01 00:00:00

  • Krabbe disease: clinical, biochemical and molecular information on six new patients and successful retrospective diagnosis using stored newborn screening cards.

    abstract：PURPOSE:To present clinical, biochemical and molecular information on six new clinically diagnosed Krabbe disease patients and assess the sensitivity of retrospective galactocerebrosidase measurement in their newborn screening samples. METHODS:Medical records were reviewed. Galactocerebrosidase activity was measured i...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2011.10.010

    authors： Puckett RL,Orsini JJ,Pastores GM,Wang RY,Chang R,Saavedra-Matiz CA,Torres PA,Zeng B,Caggana M,Lorey F,Abdenur JE

    更新日期：2012-01-01 00:00:00

  • Novel missense mutations in PNPLA2 causing late onset and clinical heterogeneity of neutral lipid storage disease with myopathy in three siblings.

    abstract：:Neutral lipid storage disease with myopathy (NLSD-M) is a rare autosomal recessive disorder characterised by an abnormal accumulation of triacylglycerol into cytoplasmic lipid droplets (LDs). NLSD-M patients are mainly affected by progressive myopathy, cardiomyopathy and hepatomegaly. Mutations in the PNPLA2 gene caus...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2015.05.001

    authors： Missaglia S,Tasca E,Angelini C,Moro L,Tavian D

    更新日期：2015-06-01 00:00:00

  • Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis.

    abstract：:Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality. Two genes have been identified for the X-linked forms (dystrophin and tafazzin), while mutations in multiple genes cause autosomal dominant DCM. Muscle LIM protein (MLP) is a member of the cysteine-rich protein (CRP) family and has been implicat...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/s1096-7192(03)00142-2

    authors： Mohapatra B,Jimenez S,Lin JH,Bowles KR,Coveler KJ,Marx JG,Chrisco MA,Murphy RT,Lurie PR,Schwartz RJ,Elliott PM,Vatta M,McKenna W,Towbin JA,Bowles NE

    更新日期：2003-09-01 00:00:00

  • Urinary glycosaminoglycans as a potential biomarker for evaluating treatment efficacy in subjects with mucopolysaccharidoses.

    abstract：:Accumulations of glycosaminoglycans (GAGs) that result from deficiencies in lysosomal hydrolases are characteristic of mucopolysaccharidoses (MPS). Enzyme replacement therapies (ERTs) are now available for several MPS diseases (MPS I, MPS II, MPS IVA, MPS VI, and MPS VII), but assessment of the efficacy of treatment c...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1016/j.ymgme.2020.02.006

    authors： Kakkis E,Marsden D

    更新日期：2020-05-01 00:00:00

  • Aripiprazole and trazodone cause elevations of 7-dehydrocholesterol in the absence of Smith-Lemli-Opitz Syndrome.

    abstract：:Screening for Smith-Lemli-Opitz Syndrome (SLOS) using elevated 7-dehydrocholesterol (7DHC) as a marker is sensitive, but not always specific. Elevations of 7DHC can be seen in patients who do not have a defect in 7-dehydrocholesterol reductase. These results have often been attributed to medication artifacts, but spec...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2013.04.004

    authors： Hall P,Michels V,Gavrilov D,Matern D,Oglesbee D,Raymond K,Rinaldo P,Tortorelli S

    更新日期：2013-09-01 00:00:00

  • Fluxomic assay-assisted diagnosis orientation in a cohort of 11 patients with myopathic form of CPT2 deficiency.

    abstract：:Carnitine palmitoyltransferase type 2 (CPT2) deficiency, a mitochondrial fatty acid oxidation disorder (MFAOD), is a cause of myopathy in its late clinical presentation. As for other MFAODs, its diagnosis may be evocated when blood acylcarnitine profile is abnormal. However, a lack of abnormalities or specificity in t...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2018.02.005

    authors： Fontaine M,Kim I,Dessein AF,Mention-Mulliez K,Dobbelaere D,Douillard C,Sole G,Schiff M,Jaussaud R,Espil-Taris C,Boutron A,Wuyts W,Acquaviva C,Vianey-Saban C,Roland D,Joncquel-Chevalier Curt M,Vamecq J

    更新日期：2018-04-01 00:00:00

  • Clinical, molecular, and cell biological aspects of Chediak-Higashi syndrome.

    abstract：:Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by variable degrees of oculocutaneous albinism, easy bruisability, and bleeding as a result of deficient platelet dense bodies, and recurrent infections, with neutropenia, impaired chemotaxis and bactericidal activity, and abnormal NK ...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1006/mgme.1999.2927

    authors： Introne W,Boissy RE,Gahl WA

    更新日期：1999-10-01 00:00:00

  • A newly generated neuronal cell model of CLN7 disease reveals aberrant lysosome motility and impaired cell survival.

    abstract：:Mutations in the CLN7/MFSD8 gene encoding the lysosomal membrane protein CLN7 are causative of CLN7 disease, an inherited neurodegenerative disorder that typically affects children. To gain insight into the pathomechanisms of CLN7 disease, we established an immortalized cell line based on cerebellar (Cb) granule neuro...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2018.09.009

    authors： von Kleist L,Ariunbat K,Braren I,Stauber T,Storch S,Danyukova T

    更新日期：2019-02-01 00:00:00

  • Combined alpha-delta platelet storage pool deficiency is associated with mutations in GFI1B.

    abstract：:Combined alpha-delta platelet storage pool deficiency is characterized by the absence or reduction in the number of both alpha granules and dense bodies. This disorder can have variable severity as well as a variable inheritance pattern. We describe two patients from unrelated families with combined alpha-delta storag...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2016.12.006

    authors： Ferreira CR,Chen D,Abraham SM,Adams DR,Simon KL,Malicdan MC,Markello TC,Gunay-Aygun M,Gahl WA

    更新日期：2017-03-01 00:00:00

  • Nonexpressing homozygotes for C282Y hemochromatosis: minority or majority of cases?

    abstract：:Genetic testing for the C282Y mutation of the HFE gene has been a major advance in the diagnosis of hereditary hemochromatosis. In most studies, more than 90% of typical hemochromatosis patients are homozygous for the C282Y mutation. Large-scale population screening studies in predominantly Caucasian populations have ...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1006/mgme.2000.3037

    authors： Adams PC

    更新日期：2000-09-01 00:00:00

  • ELMO1 variants and susceptibility to diabetic nephropathy in American Indians.

    abstract：:Variants in the engulfment and cell motility 1 gene, ELMO1, have previously been associated with kidney disease attributed to type 2 diabetes. The Pima Indians of Arizona have high rates of diabetic nephropathy, which is strongly dependent on genetic determinants; thus, we sought to investigate the role of ELMO1 polym...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2010.08.014

    authors： Hanson RL,Millis MP,Young NJ,Kobes S,Nelson RG,Knowler WC,DiStefano JK

    更新日期：2010-12-01 00:00:00

  • Dietary treatment in phenylketonuria does not lead to increased risk of obesity or metabolic syndrome.

    abstract：BACKGROUND:Little is known about the consequences of the special energy enriched diet used to treat patients with phenylketonuria (PKU) in terms of obesity and metabolic syndrome (MetSyn) development. OBJECTIVE:To investigate the prevalence of overweight and obesity, and its consequences in terms of body composition a...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2012.10.006

    authors： Rocha JC,van Spronsen FJ,Almeida MF,Soares G,Quelhas D,Ramos E,Guimarães JT,Borges N

    更新日期：2012-12-01 00:00:00

  • Developmental changes in the expression of neuronal ceroid lipofuscinoses-linked proteins.

    abstract：:Neuronal ceroid lipofuscinoses (NCL) form a distinct group of storage diseases where the normal development of the central nervous system is interrupted and neurons of the neocortex begin to degenerate. Mutations in genes encoding three lysosomal enzymes are the causes for three early-onset forms of NCLs: palmitoyl-pr...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1006/mgme.2000.3071

    authors： Suopanki J,Partanen S,Ezaki J,Baumann M,Kominami E,Tyynelä J

    更新日期：2000-09-01 00:00:00

  • Novel variants of the human flavin-containing monooxygenase 3 (FMO3) gene associated with trimethylaminuria.

    abstract：:The disorder trimethylaminuria (TMAu) often manifests itself in a body odor for individuals affected. TMAu is due to decreased metabolism of dietary-derived trimethylamine (TMA). In a healthy individual, 95% or more of TMA is converted by the flavin-containing monooxygenase 3 (FMO3, EC 1.14.13.8) to non-odorous trimet...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2009.02.006

    authors： Motika MS,Zhang J,Zheng X,Riedler K,Cashman JR

    更新日期：2009-06-01 00:00:00

  • Genetic and epigenetic regulation schemes: need for an alternative paradigm.

    abstract：:Self-organization of living cells results from the tangle of positive and negative feedback developed to ensure their homeostasis and/or their differentiation. There are three major means cellular regulation operates: the genetic, the epigenetic, and the metabolic ones. The regulation type in each of them has been ove...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1006/mgme.2000.3048

    authors： Roux-Rouquie M

    更新日期：2000-09-01 00:00:00

  • Problems in the management of urea cycle disorders.

    abstract：:Several recent reviews describe the management of urea cycle disorders. There is much agreement on diet, alternative pathway therapy, maintenance of arginine and ornithine levels in acute and chronic management, sick-day regimens, and some aspects of monitoring. However, differences remain in several areas, and physic...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1016/j.ymgme.2003.10.016

    authors： Wilcken B

    更新日期：2004-04-01 00:00:00

  • Bacterial species identification after DNA amplification with a universal primer pair.

    abstract：:The diagnosis of bacterial infections can be difficult and time consuming. Rapid and reliable molecular triage of potentially infected patients, particularly the young and the elderly, would prevent unnecessary hospitalizations, reduce associated medical costs, and improve the quality of care. Polymerase chain reactio...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.1998.2795

    authors： McCabe KM,Zhang YH,Huang BL,Wagar EA,McCabe ER

    更新日期：1999-03-01 00:00:00

  • CYP gene polymorphisms and early menarche.

    abstract：:Early age at menarche is a risk factor for breast cancer. A previous study reported a significant positive association between the CYP3A4*1B variant allele and early puberty. We investigated whether polymorphisms of the CYP3A4, CYP17, CYP1B1, and CYP1A2 genes predict the age at onset of menarche. Five hundred eighty-t...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.2001.3260

    authors： Lai J,Vesprini D,Chu W,Jernström H,Narod SA

    更新日期：2001-12-01 00:00:00

  • Rapid diagnosis of late-onset Pompe disease by fluorometric assay of alpha-glucosidase activities in dried blood spots.

    abstract：:The enzymatic defect in Pompe disease is insufficient lysosomal acid alpha-glucosidase (GAA) activity which leads to lysosomal glycogen accumulation. We recently introduced a simple and reliable method to measure GAA activity in dried blood spots using Acarbose, a highly selective alpha-glucosidase inhibitor, to elimi...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2006.12.006

    authors： Kallwass H,Carr C,Gerrein J,Titlow M,Pomponio R,Bali D,Dai J,Kishnani P,Skrinar A,Corzo D,Keutzer J

    更新日期：2007-04-01 00:00:00

  • Use of TaqI digestion may lead to incorrect molecular diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

    abstract：:Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase (CYP21) gene. For reliable and accurate mutation detection in the CYP21 gene it is important to separate the CYP21 gene from the highly homologous CYP21P pseudogene. For this, several di...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.2000.3023

    authors： Lee HH,de Wijs IJ,Sistermans EA

    更新日期：2000-08-01 00:00:00

  • Improvement in behaviour after substrate deprivation therapy with rhodamine B in a mouse model of MPS IIIA.

    abstract：:Mucopolysaccharidosis type IIIA (MPS IIIA) is a specific lysosomal storage disorder caused by an enzyme deficiency in sulphamidase, which is required for the degradation of heparan sulphate glycosaminoglycan (gag). This deficiency results in widespread gag storage and leads to severe CNS degeneration and mild somatic ...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2007.06.016

    authors： Roberts AL,Rees MH,Klebe S,Fletcher JM,Byers S

    更新日期：2007-09-01 00:00:00

  • Thoroughly modern medicine.

    abstract：:Personalized medicine is receiving increasing attention in the medical literature and lay press as one way to optimize therapy and reduce complications of treatment for almost any disorder. However, understanding the systemic complexities necessary to implement the ambitious goals of personalized medicine is unlikely ...

    journal_title：Molecular genetics and metabolism

    pub_type：

    doi：10.1016/j.ymgme.2011.07.011

    authors： Arnold GL,Vockley J

    更新日期：2011-09-01 00:00:00

  • Induction of oxidative stress in brain of glutaryl-CoA dehydrogenase deficient mice by acute lysine administration.

    abstract：:In the present work we evaluated a variety of indicators of oxidative stress in distinct brain regions (striatum, cerebral cortex and hippocampus), the liver, and heart of 30-day-old glutaryl-CoA dehydrogenase deficient (Gcdh(-/-)) mice. The parameters evaluated included thiobarbituric acid-reactive substances (TBA-RS...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2012.03.002

    authors： Seminotti B,da Rosa MS,Fernandes CG,Amaral AU,Braga LM,Leipnitz G,de Souza DO,Woontner M,Koeller DM,Goodman S,Wajner M

    更新日期：2012-05-01 00:00:00

  • P53 and IGFBP-3: apoptosis and cancer protection.

    abstract：:p53, perhaps the single most important human tumor suppressor, is commonly mutated in human cancers. Normally genotoxic stress and hypoxia activate p53, which, through DNA-specific transcription activation, transcriptional repression, and protein-protein interactions, triggers cell cycle arrest and apoptosis. One of t...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1006/mgme.2000.3008

    authors： Grimberg A

    更新日期：2000-06-01 00:00:00

  • Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1⁻/⁻ mice.

    abstract：:Lung dysfunction is an important part of the pathology of the neurodegenerative disorder, Niemann-Pick C1 (NPC1). We have studied the pulmonary disease in the Npc1(NIH/NIH) mouse model. On histology, we find large numbers of alveolar foamy macrophages but no alveolar proteinosis. Lung weight as percent of body weight ...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2011.03.001

    authors： Muralidhar A,Borbon IA,Esharif DM,Ke W,Manacheril R,Daines M,Erickson RP

    更新日期：2011-06-01 00:00:00

  • Neurocognitive functioning in adults with phenylketonuria: Report of a 10-year follow-up.

    abstract：BACKGROUND:The long-term prognosis of early treated phenylketonuria (PKU) is still under discussion. Aim of this controlled long-term study was to assess the neurological and neuropsychological outcome in adult patients with early-treated PKU. METHODS:We investigated 35 patients with early-treated classical PKU aged 2...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2018.12.011

    authors： Feldmann R,Osterloh J,Onon S,Fromm J,Rutsch F,Weglage J

    更新日期：2019-03-01 00:00:00

  • Dysregulated DNA methylation of GLA gene was associated with dysfunction of autophagy.

    abstract：:Lysosomes are an essential organ for cellular metabolism and play an important role in autophagy. We examined the association between methylation and autophagy in a severely affected female patient with Fabry disease, which is caused by mutation of the GLA gene on the X chromosome, and her two sisters, who had few sym...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2019.03.003

    authors： Yanagisawa H,Hossain MA,Miyajima T,Nagao K,Miyashita T,Eto Y

    更新日期：2019-04-01 00:00:00

  • Stop codon read-through of a methylmalonic aciduria mutation.

    abstract：:A stop codon defect in methylmalonyl-CoA mutase (resulting in a truncated unstable protein) accounts for up to 14% of mutations identified as causes of Methylmalonic aciduria. There are currently limited treatment regimes for patients with this inherited condition. We aimed to investigate the use of stop codon read-th...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2009.04.004

    authors： Buck NE,Wood L,Hu R,Peters HL

    更新日期：2009-08-01 00:00:00

  • Pilot study of mass screening for Wilson's disease in Korea.

    abstract：:Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism with copper accumulation in the liver as well as in the central nervous system. Treatment of WD includes oral chelating agents and diet and it is effective. However, once irreversible damage has occurred, the effect of treatment is diminishe...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/s1096-7192(02)00026-4

    authors： Hahn SH,Lee SY,Jang YJ,Kim SN,Shin HC,Park SY,Han HS,Yu ES,Yoo HW,Lee JS,Chung CS,Lee SY,Lee DH

    更新日期：2002-06-01 00:00:00