α-Ketoadipic aciduria — a new inborn defect of lysine degradation

1976 ◽  
pp. 271-285 ◽  
Author(s):  
H. J. Bremer ◽  
S. K. Wadman ◽  
Hildegard Przyrembel ◽  
U. Wendel ◽  
Ingrid Lombeck
Keyword(s):  
Lysine Degradation ◽  
Inborn Defect

Identification of circular RNA expression profiles and potential biomarkers for intracerebral hemorrhage

Epigenomics ◽  
2021 ◽  
Author(s):  
Congxia Bai ◽  
Tingting Liu ◽  
Yingying Sun ◽  
Hao Li ◽  
Ning Xiao ◽  
...  
Keyword(s):  
Immune System ◽  
Intracerebral Hemorrhage ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Circular Rna ◽  
Rna Expression ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Lysine Degradation ◽  
Potential Biomarkers

Aim: To investigate the expression profiles of circRNAs after intracerebral hemorrhage (ICH). Materials & methods: RNA sequencing and qRT-PCR were used to investigate and validate circRNA expression levels. Bioinformatics analysis was performed to explore potential functions of the circRNAs. Results: Expression levels of 15 circRNAs were consistently altered in patients with ICH compared with their expression levels in hypertension. Three circRNAs, hsa_circ_0001240, hsa_circ_0001947 and hsa_circ_0001386, individually or combined, were confirmed as promising biomarkers for predicting and diagnosing ICH. The circRNAs were involved mainly in lysine degradation and the immune system. Conclusion: This is the first study to report expression profiles of circRNAs after ICH and to propose that three circRNAs are potential biomarkers for ICH.

scholarly journals DHTKD1 and OGDH display substrate overlap in cultured cells and form a hybrid 2-oxo acid dehydrogenase complex in vivo

2020 ◽  
Vol 29 (7) ◽  
pp. 1168-1179 ◽  
Author(s):  
João Leandro ◽  
Tetyana Dodatko ◽  
Jan Aten ◽  
Natalia S Nemeria ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Cell Model ◽  
Glutaric Aciduria Type ◽  
Glutaric Aciduria Type 1 ◽  
Hek 293 ◽  
Acid Dehydrogenase ◽  
Lysine Degradation ◽  
Acid Dehydrogenase Complex ◽  
Dehydrogenase Complex

Abstract Glutaric aciduria type 1 (GA1) is an inborn error of lysine degradation characterized by a specific encephalopathy that is caused by toxic accumulation of lysine degradation intermediates. Substrate reduction through inhibition of DHTKD1, an enzyme upstream of the defective glutaryl-CoA dehydrogenase, has been investigated as a potential therapy, but revealed the existence of an alternative enzymatic source of glutaryl-CoA. Here, we show that loss of DHTKD1 in glutaryl-CoA dehydrogenase-deficient HEK-293 cells leads to a 2-fold decrease in the established GA1 clinical biomarker glutarylcarnitine and demonstrate that oxoglutarate dehydrogenase (OGDH) is responsible for this remaining glutarylcarnitine production. We furthermore show that DHTKD1 interacts with OGDH, dihydrolipoyl succinyltransferase and dihydrolipoamide dehydrogenase to form a hybrid 2-oxoglutaric and 2-oxoadipic acid dehydrogenase complex. In summary, 2-oxoadipic acid is a substrate for DHTKD1, but also for OGDH in a cell model system. The classical 2-oxoglutaric dehydrogenase complex can exist as a previously undiscovered hybrid containing DHTKD1 displaying improved kinetics towards 2-oxoadipic acid.

scholarly journals Functional Genomics Differentiate Inherent and Environmentally Influenced Traits in Dinoflagellate and Diatom Communities

2020 ◽  
Vol 8 (4) ◽  
pp. 567 ◽  
Author(s):  
Stephanie Elferink ◽  
Uwe John ◽  
Stefan Neuhaus ◽  
Sylke Wohlrab
Keyword(s):  
Signal Transduction ◽  
Functional Traits ◽  
Species Interactions ◽  
Marine Ecosystem ◽  
Biotic Interactions ◽  
Sulfur Cycle ◽  
Functional Responses ◽  
Physiological Importance ◽  
Metabolic Interactions ◽  
Lysine Degradation

Dinoflagellates and diatoms are among the most prominent microeukaryotic plankton groups, and they have evolved different functional traits reflecting their roles within ecosystems. However, links between their metabolic processes and functional traits within different environmental contexts warrant further study. The functional biodiversity of dinoflagellates and diatoms was accessed with metatranscriptomics using Pfam protein domains as proxies for functional processes. Despite the overall geographic similarity of functional responses, abiotic (i.e., temperature and salinity; ~800 Pfam domains) and biotic (i.e., taxonomic group; ~1500 Pfam domains) factors influencing particular functional responses were identified. Salinity and temperature were identified as the main drivers of community composition. Higher temperatures were associated with an increase of Pfam domains involved in energy metabolism and a decrease of processes associated with translation and the sulfur cycle. Salinity changes were correlated with the biosynthesis of secondary metabolites (e.g., terpenoids and polyketides) and signal transduction processes, indicating an overall strong effect on the biota. The abundance of dinoflagellates was positively correlated with nitrogen metabolism, vesicular transport and signal transduction, highlighting their link to biotic interactions (more so than diatoms) and suggesting the central role of species interactions in the evolution of dinoflagellates. Diatoms were associated with metabolites (e.g., isoprenoids and carotenoids), as well as lysine degradation, which highlights their ecological role as important primary producers and indicates the physiological importance of these metabolic pathways for diatoms in their natural environment. These approaches and gathered information will support ecological questions concerning the marine ecosystem state and metabolic interactions in the marine environment.

DEFECTIVE THYROID HORMONE BIOSYNTHESIS WITH ANOMALOUS REACTION TO THYROID THERAPY: REPORT OF A CASE

1963 ◽  
Vol 42 (3) ◽  
pp. 412-422 ◽  
Author(s):  
J. D. Wiener ◽  
G. A. Lindeboom
Keyword(s):  
Turnover Rate ◽  
Exchange Resin ◽  
Test Dose ◽  
Ion Exchange Resin ◽  
Adsorbed Protein ◽  
Thyroid Hormone Biosynthesis ◽  
Hormone Biosynthesis ◽  
Anomalous Reaction ◽  
Large Goitre ◽  
Inborn Defect

A case is presented of an euthyroid woman with an excessively large goitre, present since childhood. A distinct discrepancy was found between total protein bound iodine and butanol extractable iodine in the serum, and an elevated part of the plasma radioactivity after a test dose of 131I was not adsorbed on ion exchange resin. However, this non-adsorbed (»protein-like«) 131I was at least partly extractable with acid butanol. The fractional turnover rate of radiothyroxine was high. The possibility is raised that the pathological component was brought into the circulation as a result of an inborn defect in the thyroidal synthesis or proteolysis of thyroglobulin, and that it was composed of a number of more or less simple peptides, possibly not without some hormonal activity. The uptake of radioiodine by the thyroid was only partly suppressed by desiccated thyroid therapy, but most of the trapped radioactivity did not appear to be incorporated into organic compounds.

scholarly journals ROLE OF THE NOTCH1 GENE IN FORMATION OF AORTIC ANEURYSM

2018 ◽  
pp. 53-59
Author(s):  
O. V. Irtyuga ◽  
O. A. Freilichman ◽  
D. S. Krivonosov ◽  
A. B. Malashicheva ◽  
S. I. Tarnovskaya ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Direct Sequencing ◽  
Mutation Screening ◽  
Protein Protein Interactions ◽  
Highly Pathogenic ◽  
Targeted Mutation ◽  
Aortic Pathology ◽  
Inborn Defects ◽  
The Impact ◽  
Inborn Defect

Aim. To evaluate the impact of genetics in development of thoracic aneurysm in patients with tricuspid valve (TAV) and bicuspid aortic valve (BAV) based on the analysis and search for mutations in NOTCH1.Material and methods. In the study, 60 patients included with the dilation of thoracic aorta more than 40 mm and 200 patients with no aortic pathology, included in the comparison group. All patients underwent echocardiographic assessment on Vivid 7 (GE, USA) equipment, by standard protocol. For molecular genetics we utilized the strategy of targeted mutation screening, including the analysis of 10 of 34 exones of the gene NOTCH1, performed with the direct sequencing.Results. Patients with BAV were younger than those with no inborn defect. Arterial hypertension was verified only in every second BAV patient. Also, maximal rates of blood pressure were significantly lower in patients with inborn defects (р<0,02). As a result of genetic analysis in the studied group, in 9 patients with inborn defect and 2 patients with TAV there were 10 variants found of aminoacid replacement in 6 among 10 analyzed exones, of those 5 replacements — synonimic, and the mutation S2449R was found first time. Mutations P1227S, E1305K, R1279H and D1267N were found at the site of Notch1 protein binding with DLL4, of those 3 are highly pathogenic, that could influence the protein-protein interactions Notch1 with DLL4 leading to formation on aneurysm.Conclusion. Mutations P1227S D1267, E1305K in the gene NOTCH1, being highly pathogenic, may lead to the changes of protein functioning via Notch signalling disorder, that is more characteristic for BAV patients.

scholarly journals Massively parallel fitness profiling reveals multiple novel enzymes inPseudomonas putidalysine metabolism

2018 ◽  
Author(s):  
Mitchell G. Thompson ◽  
Jacquelyn M. Blake-Hedges ◽  
Pablo Cruz-Morales ◽  
Jesus F. Barajas ◽  
Samuel C. Curran ◽  
...  
Keyword(s):  
Tca Cycle ◽  
Central Metabolism ◽  
It Use ◽  
Catabolic Genes ◽  
Genome Wide ◽  
The Tca Cycle ◽  
A Genome ◽  
Domains Of Life ◽  
Lysine Degradation ◽  
Lysine Metabolism

AbstractDespite intensive study for 50 years, the biochemical and genetic links between lysine metabolism and central metabolism inPseudomonas putidaremain unresolved. To establish these biochemical links, we leveraged Random Barcode Transposon Sequencing (RB-TnSeq), a genome-wide assay measuring the fitness of thousands of genes in parallel, to identify multiple novel enzymes in both L- and D-lysine metabolism. We first describe three pathway enzymes that catabolize L-2-aminoadipate (L-2AA) to 2-ketoglutarate (2KG), connecting D-lysine to the TCA cycle. One of these enzymes, PP_5260, contains a DUF1338 domain, a family with no previously described biological function. Our work also identified the recently described CoA independent route of L-lysine degradation that metabolizes to succinate. We expanded on previous findings by demonstrating that glutarate hydroxylase CsiD is promiscuous in its 2-oxoacid selectivity. Proteomics of select pathway enzymes revealed that expression of catabolic genes is highly sensitive to particular pathway metabolites, implying intensive local and global regulation. This work demonstrates the utility of RB-TnSeq for discovering novel metabolic pathways in even well-studied bacteria, as well as a powerful tool for validating previous research.ImportanceP. putidalysine metabolism can produce multiple commodity chemicals, conferring great biotechnological value. Despite much research, connecting lysine catabolism to central metabolism inP. putidaremained undefined. Herein we use Random Barcode Transposon Sequencing to fill in the gaps of lysine metabolism inP. putida. We describe a route of 2-oxoadipate (2OA) catabolism in bacteria, which utilizes DUF1338 containing protein PP_5260. Despite its prevalence in many domains of life, DUF1338 containing proteins had no known biochemical function. We demonstrate PP_5260 is a metalloenzyme which catalyzes an unusual 2OA to D-2HG decarboxylation. Our screen also identified a recently described novel glutarate metabolic pathway. We validate previous results, and expand the understanding of glutarate hydroxylase CsiD by showing can it use either 2OA or 2KG as a cosubstrate. Our work demonstrates biological novelty can be rapidly identified using unbiased experimental genetics, and that RB-TnSeq can be used to rapidly validate previous results.

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