Abstract:
:Propionyl-CoA carboxylase (PCC, EC 6.4.1.3) is a mitochondrial, biotin-dependent enzyme that functions in the catabolism of branched-chain amino acids, fatty acids with odd-numbered chain lengths, and other metabolites. It catalyzes the ATP-dependent carboxylation of propionyl-CoA to d-methylmalonyl-CoA. PCC is composed of two types of subunits, likely as alpha4beta4 or alpha6beta6, with the alpha subunit containing the covalently bound biotin prosthetic group. A genetic deficiency of PCC activity causes propionic acidemia, a potentially fatal disease with onset in severe cases in the newborn period. Affected patients may have mutations of either the PCCA or PCCB gene. In this study, we have determined the structure of the human PCCA gene which, at the present time, is only partially represented in the databases. Based on reported ESTs and confirmed by RT-PCR, we also redefine the translation initiation codon to a position 75 nucleotides upstream of the currently accepted initiation codon. We show the distribution of mutations, including three identified in this study, and renumber all reported mutations to count from the new initiation codon. The gene spans more than 360 kb and consists of 24 exons ranging from 37 to 335 bp in length. The introns range in size from 104.bp to 66 kb. We have also determined the nucleotide sequence of approximately 1 kb of the 5'-flanking region upstream of the ATG translation initiation site. The proximal 400 bp of the 5'-flanking region shows a high G + C content (67%) and is part of a putative 1-kb CpG island that extends into exon 1 and part of intron 1. The putative promoter lacks a TATA box but contains two AP-1 sites and a conservatively defined consensus GC box, the latter characteristic of the core binding sequence of the Sp1 transcription factor.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Campeau E,Desviat LR,Leclerc D,Wu X,Pérez B,Ugarte M,Gravel RAdoi
10.1006/mgme.2001.3210subject
Has Abstractpub_date
2001-09-01 00:00:00pages
238-47issue
1-2eissn
1096-7192issn
1096-7206pii
S1096-7192(01)93210-Xjournal_volume
74pub_type
杂志文章abstract::Quantification of ammonia in whole blood has applications in the diagnosis and management of many hepatic diseases, including cirrhosis and rare urea cycle disorders, amounting to more than 5 million patients in the United States. Current techniques for ammonia measurement suffer from limited range, poor resolution, f...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2015.04.004
更新日期:2015-06-01 00:00:00
abstract::We report here the isolation, characterization, and chromosomal localization of the genes encoding the human and corresponding murine orthologue of solute carrier family 19A member 3 (SLC19A3). Human SLC19A3 encodes a 496-amino-acid residue protein with a predicted molecular weight of 56 kDa that shares sequence simil...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.2000.3112
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:In children with phenylketonuria (PKU), it is possible that high carbohydrate protein substitutes may adversely affect blood phenylalanine control. We evaluated if a low carbohydrate, 'ready-to-drink' protein substitute would impact on short term blood phenylalanine control, weight and appetite in children w...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ymgme.2011.09.014
更新日期:2011-01-01 00:00:00
abstract::Severe neurological deficits and mental retardation are frequently associated with disrupted ganglioside metabolism in a variety of gangliosidoses and lysosomal storage disorders. Accumulation of glycosphingolipids (GSLs) in the central nervous system (CNS) of humans and animals affected with several types of mucopoly...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.2000.3139
更新日期:2001-03-01 00:00:00
abstract::Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by pigment dilution, nystagmus, decreased visual acuity, a bleeding diathesis, and lysosomal accumulation of ceroid lipofuscin. Electron microscopic evidence demonstrating lack of platelet-dense bodies provides the sine qua non for diagno...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1006/mgme.1998.2729
更新日期:1998-10-01 00:00:00
abstract::Oxidative stress plays an important role in the pathophysiology of neurodegenerative diseases, including X-linked adrenoleukodystrophy (X-ALD). In the present work, we evaluated lipid (malondialdehyde [MDA] content) and protein (sulfhydryl and carbonyl contents) oxidative damage parameters in plasma from X-ALD patient...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.03.019
更新日期:2012-06-01 00:00:00
abstract::Cobalamin (Cbl, B(12)) is an essential micronutrient required to fulfill the enzymatic reactions of cytosolic methylcobalamin-dependent methionine synthase and mitochondrial adenosylcobalamin-dependent methylmalonyl-CoA mutase. Mutations in the MMACHC gene (cblC complementation group) disrupt processing of the upper-a...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2011.03.008
更新日期:2011-07-01 00:00:00
abstract::Pompe disease results from inherited deficiency of the enzyme acid alpha-glucosidase resulting in lysosomal accumulation of glycogen primarily in skeletal muscle. Reported is the first case in which a donor with late onset Pompe disease (LOPD) was successfully used for deceased donor liver and kidney transplantation. ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2015.05.007
更新日期:2015-08-01 00:00:00
abstract::Orthotopic liver transplant (OLT) significantly improves patient outcomes in maple syrup urine disease (MSUD; OMIM: 248600), yet organ shortages point to the need for alternative therapies. Hepatocyte transplantation has shown both clinical and preclinical efficacy as an intervention for metabolic liver diseases, yet ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2013.02.011
更新日期:2013-06-01 00:00:00
abstract::Globoid cell leukodystrophy (GLD, Krabbe disease), is an autosomal recessive, neurodegenerative disease caused by the deficiency of the lysosomal enzyme galactocerebrosidase (GALC). In the absence of GALC, the toxic metabolite psychosine accumulates in the brain and causes the death of the myelin-producing cells, olig...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.05.021
更新日期:2012-09-01 00:00:00
abstract:RATIONALE:We previously reported that mitogen-activated protein kinase phosphatase-1 (MKP-1) expression is necessary for oxidized phospholipids to induce monocyte chemoattractant protein-1 (MCP-1) secretion by human aortic endothelial cells. We also reported that inhibition of tyrosine phosphatases including MKP-1 amel...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.05.009
更新日期:2010-09-01 00:00:00
abstract::Human reproductive function is regulated mainly by luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Mutations of the human LH/ chorionic gonadotropin receptor (LHR) and the FSH receptor (FSHR) leading to either constitutive activation or inactivation of the receptors have been identified. All activatin...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1006/mgme.1997.2650
更新日期:1998-02-01 00:00:00
abstract::Mutations in DGUOK result in mitochondrial DNA (mtDNA) depletion and may present as neonatal liver failure. Neonatal hemochromatosis (NH(1)) is a liver disorder of uncertain and varied etiology characterized by hepatic and non-reticuloendothelial siderosis. To date, deoxyguanosine kinase (dGK(2)) deficiency has not be...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2011.03.006
更新日期:2011-07-01 00:00:00
abstract::Classic phenylketonuria (PKU) is characterized by severe mental retardation in untreated individuals and mild neurocognitive abnormalities in some early treated adults. The exact biochemical mechanisms underlying this neurotoxicity remain undetermined. Several theories implicate abnormal cerebral energy utilization an...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2005.06.010
更新日期:2006-03-01 00:00:00
abstract::Inborn defects of cholesterol biosynthesis are metabolic disorders presenting with multi-organ and tissue anomalies. An autosomal recessive defect involving the demethylating enzyme C4-methyl sterol (SC4MOL) has been reported in only 4 patients so far. In infancy, all patients were affected by microcephaly, bilateral ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2017.06.013
更新日期:2017-08-01 00:00:00
abstract::Thymidine kinase 2 (TK2), encoded by the TK2 gene on chromosome 16q22, is one of the deoxyribonucleoside kinases responsible for the maintenance of mitochondrial deoxyribonucleotide pools. Defects in TK2 mainly cause a myopathic form of the mitochondrial DNA depletion syndrome (MDDS). Currently, only point mutations a...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2009.09.003
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Telomeres may be considered markers of biological aging, shorter telomere length is associated with some age-related diseases; in several studies short telomere length has also been associated to obesity in adults and adolescents. However the relationship between telomere complex functions and obesity is s...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2016.04.003
更新日期:2016-06-01 00:00:00
abstract::In Duchenne muscular dystrophy (DMD), identification of one nonsense mutation in the DMD gene has been considered an endpoint of genetic diagnosis. Here, we identified two closely spaced nonsense mutations in the DMD gene. In a Malaysian DMD patient two nonsense mutations (p.234S>X and p.249Q>X, respectively) were ide...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2011.04.002
更新日期:2011-07-01 00:00:00
abstract::Resistance to thyroid hormone (RTH) is an inherited syndrome of reduced tissue responsiveness to thyroid hormone (T3) caused by mutations in the thyroid hormone receptor beta (TRbeta). The index patient of the family reported here, a 17-year-old woman, came to medical attention because of a diffuse goiter, short statu...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.2000.3088
更新日期:2000-11-01 00:00:00
abstract::Isolated methylmalonic aciduria (MMA) results either from a defect in the mitochondrial enzyme methylmalonylCoA mutase (MCM), or in the intracellular conversion of vitamin B12 (cobalamin) into its active coenzyme adenosylcobalamin (AdoCbl). Mutations in the MMAB gene affect the function of the enzyme ATP:cob(I)alamin ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2013.04.020
更新日期:2013-09-01 00:00:00
abstract::Infantile hepatopathies are life-threatening liver disorders that manifest in the first few months of life. We report on a consanguineous Irish Traveller family that includes six individuals presenting with acute liver failure in the first few months of life. Additional symptoms include anaemia, renal tubulopathy, dev...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.04.017
更新日期:2012-07-01 00:00:00
abstract::Multiple sulfatase deficiency (MSD) is an ultra-rare neurodegenerative disorder that results in defective sulfatase post-translational modification. Sulfatases in the body are activated by a unique protein, formylglycine-generating enzyme (FGE) that is encoded by SUMF1. When FGE is absent or insufficient, all 17 known...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2018.01.005
更新日期:2018-03-01 00:00:00
abstract::Mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) is a rare mitochondrial disorder that has previously been associated with mutations in PUS1 and YARS2. In the present report, we describe a 6-year old male with an MLASA plus phenotype. This patient had features of MLASA in the setting of develop...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2014.06.004
更新日期:2014-11-01 00:00:00
abstract::Glut-1 facilitates the diffusion of glucose across the blood-brain barrier and is responsible for glucose entry into the brain. Impaired glucose transport across the blood-brain barrier results in Glut-1 deficiency syndrome (Glut-1 DS, OMIM 606777), characterized in its most severe form by infantile seizures, developm...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.03.007
更新日期:2010-06-01 00:00:00
abstract::Saposin A is a post-translation product of the prosaposin (PSAP) gene that serves as an activator protein of the galactocerebrosidase (GALC) enzyme, and is necessary for the degradation of certain glycosphingolipids. Deficiency of saposin A leads to a clinical picture identical to that of early-infantile Krabbe diseas...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2019.08.001
更新日期:2020-02-01 00:00:00
abstract::To elucidate the basis of mucopolysaccharidosis type VI (MPS VI) from the point of view of enzyme structure, we built structural models of mutant N-acetylgalactosamine-4-sulfatase (4S) resulting from 34 missense mutations (17 severe and 17 attenuated), and analyzed the influence of each amino acid replacement on the s...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2007.11.017
更新日期:2008-04-01 00:00:00
abstract::Inherited defects in glutaryl-CoA dehydrogenase cause the neurometabolic disease, glutaric acidemia type I. Five of over 80 mutations that have been identified are located in a carboxyl-terminal domain. The five mutations were generated by site directed mutagenesis and expressed in Escherichia coli. The mutant dehydro...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/s1096-7192(03)00109-4
更新日期:2003-08-01 00:00:00
abstract::Gaucher disease is caused by the defective catabolism of the simple glycosphingolipid, glucosylceramide (GlcCer), due to mutations in the GBA1 gene which encodes for acid β-glucosidase (GCase), the lysosomal enzyme that degrades GlcCer. Today, Gaucher disease patients are routinely treated with recombinant GCase, in a...
journal_title:Molecular genetics and metabolism
pub_type: 传,历史文章,杂志文章,评审
doi:10.1016/j.ymgme.2016.11.390
更新日期:2017-01-01 00:00:00
abstract::In about 20-30% of phenylketonuria (PKU) patients, phenylalanine (Phe) levels can be controlled by cofactor 6R-tetrahydrobiopterin (BH(4)) administration. The phenylalanine hydroxylase (PAH) genotype has a predictive value concerning BH(4)-response and therefore a correct assessment of the mutation molecular pathology...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.05.013
更新日期:2012-08-01 00:00:00
abstract::This study describes the phenotype/genotype analyses of 56 probands with a juvenile onset, some of which had atypical features of neuronal ceroid lipofuscinosis, collected at the New York State Institute for Basic Research (IBR). In this group, we found probands with abundant curvilinear profiles in lysosomal storage ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.1999.2814
更新日期:1999-04-01 00:00:00