Ask about this productRelated genes to: GCDH Blocking Peptide
- Gene:
- GCDH NIH gene
- Name:
- glutaryl-CoA dehydrogenase
- Previous symbol:
- -
- Synonyms:
- ACAD5
- Chromosome:
- 19p13.13
- Locus Type:
- gene with protein product
- Date approved:
- 1992-12-17
- Date modifiied:
- 2017-12-15
Related products to: GCDH Blocking Peptide
Related articles to: GCDH Blocking Peptide
- Chronic kidney disease is largely driven by environmental exposure such as per- and polyfluoroalkyl substances (PFAS). Mitochondrial proteins, whose homeostasis can be affected by PFAS, largely participate in the progression of renal damage. Despite this connection, the direct mitochondria-xenobiotics interaction and linking mechanisms are still lacking. In this study, integrative thermal proteome profiling and limited proteolysis-mass spectrometry was used to identify the direct protein targets of sodium p-perfluorous nonenoxybenzenesulfonate (OBS), a typical emerging PFAS, to pose nephrotoxicity. OBS elicited distinct renal injury phenotype in mice. Dihydrolipoamide succinyltransferase (DLST) and glutaryl-CoA dehydrogenase (GCDH) were identified as critical targets of OBS. Validation through cellular thermal shift assay, surface plasmon resonance and molecular docking confirmed that OBS bound with these two proteins. As a result, their expressions were significantly downregulated. Metabolomics revealed that the decrease in DLST and GCDH expressions subsequently inhibited tricarboxylic acid cycle and lysine degradation, which synergistically suppressed mitochondrial respiratory chain to hinder ATP production and depress methionine metabolism, eventually leading to the damage phenotype. Upon in situ overexpression of DLST and GCDH in kidney, mice exposed to OBS exhibited reduced level of mitochondrial damage and metabolic abnormalities, as well as mitigated kidney injury. This study discloses that OBS directly targets on mitochondrial proteins to disrupt the cascade of multiple metabolism processes and promotes renal impairment, proving evidence on the direct interaction between mitochondria and pollutants, and certifying mitochondrial proteins as potential therapeutic targets against environmental exposure induced toxicities. - Source: PubMed
Publication date: 2026/05/14
Lyu YangGuo RuyuGui BingxinZhong WenjueZhu Lingyan - Glutaric acidemia type 1 (GA-1) is a severe, life-threatening organic acidemia. This study aimed to evaluate fetal ultrasound findings as early clues for GA-1. - Source: PubMed
Publication date: 2026/05/10
Wang ShunanMeng XiangliZhang XiaoxiaoLi LuluTang YueKong YuanyuanWu Qingqing - Glutaric acidemia type 1 (GA1) is an autosomal recessive neurometabolic disorder caused by pathogenic variants in glutaryl-CoA dehydrogenase (GCDH), with variable clinical severity despite early biochemical detectability. Population-specific mutational spectra and genotype-phenotype correlations remain insufficiently defined in infantile-onset disease. Therefore, this study aimed to define the GCDH variant spectrum in GA1 patients with mild hepatopathy and assess genotype-phenotype correlations. We performed integrated clinical, biochemical, and molecular characterization of 15 unrelated patients with infantile-onset GA1. Whole-exome sequencing (WES) was performed for all participants, and the resulting data were compared with the reference sequence of the GCDH gene. All patients presented within the first 6 months of life with macrocephaly, seizures, dystonia, and feeding difficulties. Neurological impairment and mild hepatopathy were variably observed, and one patient developed an acute encephalopathic crisis. Six homozygous GCDH variants were identified, predominantly missense. A common variant, c.541G>C (p.Glu181Gln), accounted for 73.3% of cases and defined a consistent phenotype of early macrocephaly and movement disorder with frequent mild hepatic involvement, suggesting regional enrichment and raising the possibility of a founder effect that warrants confirmation in future haplotype studies. A truncating variant, c.382C>T (p.Arg128Ter), was associated with severe early encephalopathy. Exon 6 represented a mutational hotspot. Biochemically, all patients showed elevated urinary glutaric and 3-hydroxyglutaric acids, increased glutarylcarnitine, and low-to-normal free carnitine, with higher metabolite levels in clinically more severe cases. All variants were pathogenic or likely pathogenic and extremely rare in population databases. This cohort reveals a striking predominance of the GCDH c.541G>C variant and establishes a clear biochemical signature with genotype-associated clinical patterns in infantile-onset GA1. These findings support a population-specific mutational spectrum, refine genotype-phenotype correlations, and underscore the importance of early molecular diagnosis to guide targeted neurological and hepatic monitoring as well as regional screening strategies. - Source: PubMed
Publication date: 2026/04/18
Beyzaei ZahraGeramizadeh BitaDehghani Seyed MohsenInaloo SorourWeiskirchen Ralf - Inborn errors of metabolism (IEM) are frequently underdiagnosed in low-resource settings due to limited diagnostic infrastructure. We hypothesized that an integrated clinical-genomic approach could improve diagnosis and management of these conditions. Nineteen Pakistani families with clinically suspected IEM underwent systematic clinical assessment, available biochemical testing, and whole-exome sequencing (WES). Variants were classified according to ACMG/AMP guidelines using evidence from population databases, in silico prediction tools, segregation analysis, and genotype-phenotype correlation. Clinical diagnoses and management strategies were reassessed based on molecular findings. WES provided a molecular diagnosis in 90% (17/19) of families and enabled targeted therapeutic interventions in 70% (13/19). However, clinical outcomes were variable due to advanced disease in some cases and limited follow-up. Seven novel variants were identified in CYP27B1, DYM, MTTP, ALDH3A2, USP53, BRAF, and JAG1, while twelve recurrent mutations were detected in PIGN, GCDH, CLCN7, RNASEH2C, ABCB11, MPV17, IDUA, SMPD1, FBP1, SLC37A4, ACADM, and UGT1A1. Integrating genomic findings with clinical reassessment improved diagnostic precision. An integrated clinical-genomic approach enabled accurate diagnosis of pediatric IEM in resource-limited settings, with particular utility in children with metabolic disorders in a consanguineous population. Identification of both novel and recurrent variants expanded the genotypic and phenotypic spectrum of these disorders and highlighted the clinical utility of genomic diagnostics in optimizing patient care. - Source: PubMed
Publication date: 2026/04/13
Mansoor SumreenaAbid SabeenImran MuhammadMalik Munir IqbalAli QamarHussain ShanawazAli Hafiz AsimMasood YasserChoudhry ShehlaQamar RaheelAzam Maleeha - Glutaric aciduria type 1 is caused by inherited deficiency of glutaryl-CoA dehydrogenase and subsequent accumulation of neurotoxic metabolites. Clinically, the disease is characterized by striatal damage and dystonic movement disorder in untreated infants. Despite newborn screening and pre-symptomatic therapy start, about one-third of patients still develop neurological symptoms. Furthermore, progressive white matter changes and chronic kidney disease highlights the need for improved therapies. To elucidate the potential of substrate reduction therapy for GA1 we investigated whether aminoadipate-semialdehyde synthetase, the first enzyme of the lysine oxidation pathway, could serve as therapeutic target. Therefore, we studied whether knockout (KO) mice, a known animal model for GA1, were rescued by additional knockout of . KO mice were clinically indistinguishable from wild-type mice and showed a marked reduction of glutaric acid in brain (20.9 µg/mg protein vs. 59.2 µg/mg protein; = 0.001), liver (23.5 µg/mg protein vs. 104.8 µg/mg protein; = 0.001), and urine (11.9 mol/mol creatinine vs. 166.5 mol/mol creatinine; = 0.001). The effect was less pronounced for 3-hydroxyglutaric acid. Unlike KO mice, KO mice did not develop a severe phenotype under high-lysine diet. In conclusion, knockout of partially rescues the severe phenotype of KO mice, providing a potential therapeutic target. - Source: PubMed
Publication date: 2026/03/31
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