The metabolic effect of α-ketoisocaproic acid: in vivo and in vitro studies

Farias, Hémelin Resende; Gabriel, Joice R; Cecconi, M.; Lemos, Isabela S; Rezende, Victória Linden De; Wessler, Leticia B.; Duarte, Mariane Bernardo; Scaini, Giselli; Oliveira, Jade de; Streck, Emílio L.

doi:10.1007/s11011-020-00626-y

Cited by 11 publications

(10 citation statements)

References 31 publications

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“…Results for the pediatric groups (oral/enteral vs IV) were: percentage reaching normalization (83.1%, n = 54 vs 85.7%, n = 12); mean (±SD) time to first leucine normalization (68.3 hours [±53.4] vs 84.1 hours [±59.8]); and mean (±SD) time to episode resolution (8.8 days (±6) vs 6.8 days (±3.6), P = NS). In the Kaplan-Meier analysis (Figure 3A), median (95% CI) time to episode resolution was 7 days (6-9) for the oral/enteral group and 5 days (5)(6)(7)(8)(9)(10)(11) for the IV group (log-rank test P = .24). The duration of hospitalization was the same in both treatment groups (mean 6.6 days).…”

Section: Age-category Analysismentioning

confidence: 99%

“…2,3 Although the clinical phenotype can vary in severity, generally MSUD is characterized by feeding difficulties soon after birth, which, if untreated, result in seizures, coma, development delays, and irreversible neurologic damage or death. [4][5][6] The neurotoxicity is caused by accumulation of leucine and its metabolite, α-ketoisocaproic acid, 7,8 which causes profound metabolic alterations and impairs energy homeostasis. [9][10][11] If diagnosed and treated early, prognosis is generally good.…”

Section: Introductionmentioning

confidence: 99%

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Real‐world management of maple syrup urine disease (MSUD) metabolic decompensations with branched chain amino acid‐free formulas in France and Germany: A retrospective observational study

et al. 2021

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Maple syrup urine disease (MSUD) is a rare inborn metabolic disorder, managed with a strict protein‐restricted diet. At any time or age patients may still experience metabolic decompensations, requiring administration of branched chain amino acid (BCAA)‐free formula to reduce leucine levels. This retrospective observational study of 126 decompensation episodes from 54 MSUD patients treated at five centers in France and Germany from 2010 to 2016, describes episodes and outcomes for patients stratified into groups who received enteral/oral or intravenous (IV) BCAA‐free formula, and by pediatric or adult age categories. IV administration of BCAA‐free formula was required in cases of gastric intolerance (33%), refusal to undergo nasogastric tubing (31%), “emergency” (14%) or coma patients (8%), and as prophylaxis before surgery (6%). Overall, mean duration of hospitalization was 6.6 days with oral/enteral BCAA‐free formula and 5.4 days with IV formula. Leucine levels at discharge decreased by a mean of 548.5 μmol/L (69.3%) in the oral/enteral group and 657.2 μmol/L (71.3%) in the IV group. In the pediatric subgroup, there were no marked differences between administration groups on any outcome. In the adult subgroup, mean time to episode resolution was 15.8 days in the oral/enteral group and 7.7 days in the IV group (P = .008); mean duration of hospitalization was 6 days in the oral/enteral group and 4.6 days in the IV group (P = NS). Overall, seven serious adverse events in two patients were reported, of which only nausea and vomiting were treatment related.

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Section: Age-category Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Real‐world management of maple syrup urine disease (MSUD) metabolic decompensations with branched chain amino acid‐free formulas in France and Germany: A retrospective observational study

et al. 2021

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“…Ketoleucine is an abnormal metabolite caused by incomplete breakdown of branched‐chain amino acids and is a metabolic toxin. Previous studies have focused on maple syrup urine disease (MSUD) 51 . In this study, we found for the first time that ketoleucine levels were downregulated in the FF of EM patients, which may suggest a new related pathway.…”

Section: Discussionmentioning

confidence: 51%

Nontargeted metabolomics analysis of follicular fluid in patients with endometriosis provides a new direction for the study of oocyte quality

Wei

Zhang

et al. 2023

MedComm

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Endometriosis is a common, estrogen‐dependent chronic gynecological disease that endangers the reproductive system and systemic metabolism of patients. We aimed to investigate the differences in metabolic profiles in the follicular fluid between infertile patients with endometriosis and controls. A total of 25 infertile patients with endometriosis and 25 infertile controls who were similar in age, BMI, fertilization method and ovulation induction treatment were recruited in this study. Metabolomics analysis of follicular fluid was performed by two methods of high‐performance liquid chromatography tandem mass spectrometry. There were 36 upregulated and 17 downregulated metabolites in the follicular fluid of patients in the endometriosis group. KEGG pathway analysis revealed that these metabolites were enriched in phenylalanine, tyrosine and tryptophan biosynthesis, aminoacyl‐tRNA biosynthesis, phenylalanine metabolism and pyrimidine metabolism pathways. A biomarker panel consisting of 20 metabolites was constructed by random forest, with an accuracy of 0.946 and an AUC of 0.988. This study characterizes differences in follicular fluid metabolites and associated pathway profiles in infertile patients with endometriosis. These findings can provide a better comprehensive understanding of the disease and a new direction for the study of oocyte quality, as well as potential metabolic markers for the prognosis of endometriosis.

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“…KIC is a neurotoxic factor, the acute accumulation of which reduces brain-derived neurotrophic factor and nerve growth factor, meanwhile causing damage to mitochondrial homeostasis and even leading to long-term cognitive deficits. 64 A similar increase of KIC was also observed in patients with Parkinson's disease, 65 reflecting an ongoing process of neurotoxicity and degeneration. Together, we concluded that a specific metabolic signature existed in NMOSD, which has been verified in other CNS disorders such as traumatic brain injury, 11 seizures, 66 glioblastoma, 67 Parkinson's disease, 65 and schizophrenia.…”

Section: Resultsmentioning

confidence: 58%

Comprehensive Metabolic Fingerprints Characterize Neuromyelitis Optica Spectrum Disorder by Nanoparticle-Enhanced Laser Desorption/Ionization Mass Spectrometry

Chen,

Yu,

Hao

et al. 2023

ACS Nano

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Timely screening of neuromyelitis optica spectrum disorder (NMOSD) and differential diagnosis from myelin oligodendrocyte glycoprotein associated disorder (MOGAD) are the keys to improving the quality of life of patients. Metabolic disturbance occurs with the development of NMOSD. Still, advanced tools are required to probe the metabolic phenotype of NMOSD. Here, we developed a fast nanoparticle-enhanced laser desorption/ionization mass spectrometry assay for multiplexing metabolic fingerprints (MFs) from trace plasma and cerebrospinal fluid (CSF) samples in 30 s. Machine learning of the plasma MFs achieved the timely screening of NMOSD from healthy donors with an area under receiver operator characteristic curve (AUROC) of 0.998, and it comprehensively revealed the dysregulated neurotransmitter and energy metabolisms. Combining comprehensive MFs from both plasma and CSF, we constructed an integrated panel for differential diagnosis of NMOSD versus MOGAD with an AUROC of 0.923. This approach demonstrated performance superior to that of human experts in classifying two diseases, especially in antibody assay-limited regions. Together, this approach provides an advanced nanomaterial-based tool for identifying vulnerable populations below the antibody threshold of aquaporin-4 positivity.

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The metabolic effect of α-ketoisocaproic acid: in vivo and in vitro studies

Cited by 11 publications

References 31 publications

Real‐world management of maple syrup urine disease (MSUD) metabolic decompensations with branched chain amino acid‐free formulas in France and Germany: A retrospective observational study

Real‐world management of maple syrup urine disease (MSUD) metabolic decompensations with branched chain amino acid‐free formulas in France and Germany: A retrospective observational study

Nontargeted metabolomics analysis of follicular fluid in patients with endometriosis provides a new direction for the study of oocyte quality

Comprehensive Metabolic Fingerprints Characterize Neuromyelitis Optica Spectrum Disorder by Nanoparticle-Enhanced Laser Desorption/Ionization Mass Spectrometry

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