Detection of Lipoprotein X (LpX): A challenge in patients with severe hypercholesterolaemia

Ćwiklińska, Agnieszka; Mickiewicz, Agnieszka; Kowalski, Robert; Kortas-Stempak, Barbara; Kuchta, Agnieszka; Mucha, Krzysztof; Makowiecki, M; Gliwińska, Anna; Lewandowski, Konrad; Pęczek, Łukasz; Fijałkowski, Marcin; M, Gruchała; Jankowski, Michał

doi:10.1530/ey.18.12.15

Cited by 5 publications

(9 citation statements)

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“…− were their major fragment, which was in line with the fragmentation patterns of free 12HBAs (Figures 2D,E and S8A). 16 Also, characteristic fragments could be observed in the MS/MS spectra of the remaining 9 potential 12HBAs (Figure S9). In contrast, such a fragmentation mechanism was not present for non-12HBAs, as exemplified by peak 12 that was verified to be αMCA (3α,6β,7α-hydroxyl) by standards (Figure S8B).…”

Section: Development Of 12α-hsdh-driven Lc−hrms Approach For Identify...mentioning

confidence: 97%

“…As previous described, the unique fragmentation pattern occurs only in free 12HBAs, whereas for conjugated 12HBAs the amide modification of the 24-carboxylgroups would submerge the effect fragmentations of 12-hydroxyl groups. 16 In this regard, our strategy was not subject to such limitations, as evidenced by TDCA (3α,12α-hydroxyl) (Figure S10). The validation results of the 48 12HBAs candidates were summarized in Table S6.…”

Section: Development Of 12α-hsdh-driven Lc−hrms Approach For Identify...mentioning

confidence: 99%

“…− for free 12HBAs. 16 Unfortunately, such a mechanism is not observed in conjugated types, which account for approximately half of the total BAs pool. Chemical derivatization 17−20 represents another approach for the separation and identification of structural analogues, but the difficulty lies in finding a chemoselective reagent that demonstrates specificality toward the functional group at a particular site.…”

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confidence: 99%

“…13,14 In this regard, the distinct fragmentation mechanism provides an important reference for their distinguishment. 15,16 Previous studies have reported well-defined characteristic fragmentations of…”

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confidence: 99%

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Enzyme-Driven LC–HRMS Approach for Specific Recognition of 12α-Hydroxy Bile Acids

Zhao,

Zheng,

Chen

et al. 2024

Anal. Chem.

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The synthesis of 12α-hydroxylated bile acids (12HBAs) and non-12α-hydroxylated bile acids (non-12HBAs) occurs via classical and alternative pathways, respectively. The composition of these BAs is a crucial index for pathophysiologic assessment. However, accurately differentiating 12HBAs and non-12HBAs is highly challenging due to the limited standard substances. Here, we innovatively introduce 12α-hydroxysteroid dehydrogenase (12α-HSDH) as an enzymatic probe synthesized by heterologous expression in Escherichia coli, which can specifically and efficiently convert 12HBAs in vitro under mild conditions. Coupled to the conversion rate determined by liquid chromatography-high resolution mass spectrometry (LC−HRMS), this enzymatic probe allows for the straightforward distinguishing of 210 12HBAs and 312 non-12HBAs from complex biological matrices, resulting in a BAs profile with a well-defined hydroxyl feature at the C12 site. Notably, this enzyme-driven LC-HRMS approach can be extended to any molecule with explicit knowledge of enzymatic transformation. We demonstrate the practicality of this BAs profile in terms of both revealing cross-species BAs heterogeneity and monitoring the alterations of 12HBAs and non-12HBAs under asthma disease. We envisage that this work will provide a novel pattern to recognize the shift of BA metabolism from classical to alternative synthesis pathways in different pathophysiological states, thereby offering valuable insights into the management of related diseases.

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Section: Development Of 12α-hsdh-driven Lc−hrms Approach For Identify...mentioning

confidence: 97%

Section: Development Of 12α-hsdh-driven Lc−hrms Approach For Identify...mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Enzyme-Driven LC–HRMS Approach for Specific Recognition of 12α-Hydroxy Bile Acids

Zhao,

Zheng,

Chen

et al. 2024

Anal. Chem.

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“…OXA1 is a member of the Oxa1/YidC/Alb3 protein family, which was originally identified in yeast (Bauer et al, 1994;Hell et al, 2001). Yeast Oxa1 and its human homologue OXA1L are integral proteins in the IMM, which interact with the mitoribosome through their C-terminal domain (Jia et al, 2003;Szyrach et al, 2003). This interaction docks the ribosome to the membrane, facilitating the insertion of the nascent polypeptides in the IMM.…”

Section: Co-translational Insertion Of the Peptides In The Inner Mito...mentioning

confidence: 99%

Molecular pathways in mitochondrial disorders due to a defective mitochondrial protein synthesis

Antolínez-Fernández,

Esteban-Ramos,

Fernández-Moreno

et al. 2024

Front. Cell Dev. Biol.

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Mitochondria play a central role in cellular metabolism producing the necessary ATP through oxidative phosphorylation. As a remnant of their prokaryotic past, mitochondria contain their own genome, which encodes 13 subunits of the oxidative phosphorylation system, as well as the tRNAs and rRNAs necessary for their translation in the organelle. Mitochondrial protein synthesis depends on the import of a vast array of nuclear-encoded proteins including the mitochondrial ribosome protein components, translation factors, aminoacyl-tRNA synthetases or assembly factors among others. Cryo-EM studies have improved our understanding of the composition of the mitochondrial ribosome and the factors required for mitochondrial protein synthesis and the advances in next-generation sequencing techniques have allowed for the identification of a growing number of genes involved in mitochondrial pathologies with a defective translation. These disorders are often multisystemic, affecting those tissues with a higher energy demand, and often present with neurodegenerative phenotypes. In this article, we review the known proteins required for mitochondrial translation, the disorders that derive from a defective mitochondrial protein synthesis and the animal models that have been established for their study.

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Ligands as a Tool to Tune the Toxicity of Cu on Bacteria: from Boosting to Silencing

Zuily,

Lahrach,

Falcone

et al. 2023

Copper Bioinorganic Chemistry

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Copper is an essential micronutrient for most living beings including bacteria. This is mainly due to essential roles of catalytic Cu-centers in enzymes. However, an excess of Cu is toxic and thereby used over centuries as a powerful antimicrobial agent. Bacteria developed several systems to detect Cu and protect themselves from high intracellular Cu concentration, namely via Cu-extrusion and/or Custorage. Several Cu-detoxification systems have been described and new ones are still being discovered. Progress has also been made in understanding the molecular mechanism of Cu-toxicity by identifying target macromolecules. Nevertheless, the importance of each mechanism is bacteria-and environment-dependent paving the way for new findings. The chemical reactivity of Cu can be modulated by its coordination environment in a complex with a ligand (L) and this opens large opportunities to tune the Cu-ligand complexes (Cu-L) via ligand design. For instance, boosting the toxicity of Cu ions toward bacteria was promoted by several small organic ligands. These ligands can make Cu-L complexes with different properties in terms of coordinating atoms (S, N, O), Cu to L stoichiometry, ligand denticity, thermodynamic stability, kinetic inertia and redox potential. However, one common feature shared by Cu-L complexes which efficiently boost Cu-toxicity is the ability of Cu-L to cross the two bacterial membranes and to release the Cu in the cytosol. If this property is required to improve bacteria killing is not clear yet, but considering the ever-growing resistance of bacteria, it would be interesting in the future to try to boost Cu-toxicity via unprecedented mechanisms.

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Detection of Lipoprotein X (LpX): A challenge in patients with severe hypercholesterolaemia

Cited by 5 publications

References 0 publications

Enzyme-Driven LC–HRMS Approach for Specific Recognition of 12α-Hydroxy Bile Acids

Enzyme-Driven LC–HRMS Approach for Specific Recognition of 12α-Hydroxy Bile Acids

Molecular pathways in mitochondrial disorders due to a defective mitochondrial protein synthesis

Ligands as a Tool to Tune the Toxicity of Cu on Bacteria: from Boosting to Silencing

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