Branched-chain alpha-keto acid dehydrogenase (BCKDH), a multienzyme complex, plays a key role in branched-chain amino acid catabolism. However, it remains unclear whether expression of each subunit is coordinately regulated in plants, which should be important for the efficient assembly of subunits into a functional multienzyme complex. We show that the transcripts from the Arabidopsis E1alpha subunit gene accumulated in dark-adapted leaves and in sugar-starved suspension cells. These results are complementary to our previous report that the transcripts for the E1beta and E2 subunit genes accumulated in sugar-starved cells. Expression of the E1alpha gene is likely to be regulated by hexokinase-mediated sugar signaling, indicating that sugar plays a regulatory role in the coordinated expression of BCKDH subunit genes. Furthermore, Leu and its metabolite alpha-ketoisocaproate have synergistic effects on the enhanced expression of BCKDH subunit genes under sugar starvation. We hence suggest that branched-chain amino acids activate their own degradation pathway in sugar-starved cells through co-induction of each subunit gene of BCKDH.
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http://dx.doi.org/10.1016/s0014-5793(01)02536-4 | DOI Listing |
Alzheimers Dement
December 2024
NeuroGenomics & Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.
Background: Brain, cerebrospinal fluid (CSF), and plasma metabolomics have been informative in identifying disrupted metabolism pathways in Alzheimer's disease (AD). However, many AD-focused metabolomics studies profiled a relatively small number of individuals and metabolites, especially for CSF. In addition, past studies were limited to one or two tissues.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Background: Alzheimer's disease (AD) is a neurodegenerative disorder with significant environmental factors, including diet, that influence its onset and progression. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored the KD's molecular impact for markers of AD therapeutic potential. The BEAM diet study simultaneously profiled the KD's effect on the lipidome, blood and cerebrospinal metabolome, and microbiome of both cognitively impaired and cognitively normal individuals.
View Article and Find Full Text PDFBackground: Blood-based biomarkers for dementia are gaining attention due to their non-invasive nature and feasibility in regular healthcare settings. Here, we explored the associations between 249 metabolites with all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) and assessed their predictive potential.
Method: This study included 274,160 participants from the UK Biobank.
Alzheimers Dement
December 2024
University of California, Los Angeles, Los Angeles, CA, USA.
Background: Alzheimer's Disease (AD) is a chronic, incurable neurodegenerative condition characterized by extensive systemic, cellular, and molecular abnormalities. One such aspect recent studies have highlighted is the reduction in plasma branched-chain amino acid (BCAA) concentrations, identifying them as a potential emerging marker for the disease. Although BCAAs have been implicated in the pathogenesis of AD, their utility in clinical prognosis remains unexplored.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
NYU Grossman School of Medicine, New York, NY, USA.
Background: Non-human primates (NHP) serve as an important bridge for testing therapeutic agents that have been previously shown to be effective in transgenic mouse models. Our earlier published data using an NHP model of sporadic AD-related pathology that develops abundant cerebral amyloid angiopathy (CAA), squirrel monkeys (SQMs), indicates that chronic treatment with TLR9 agonist, class B CpG ODN, safely ameliorates CAA while promoting cognitive benefits. In the present study, we intended to delineate alterations in brain metabolome induced by chronic CpG ODN administration in order to provide further insight into CpG ODN immunomodulatory capabilities.
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