Metabolites are prone to damage, either via enzymatic side reactions, which collectively form the underground metabolism, or via spontaneous chemical reactions. The resulting non-canonical metabolites that can be toxic, are mended by dedicated "metabolite repair enzymes." Deficiencies in the latter can cause severe disease in humans, whereas inclusion of repair enzymes in metabolically engineered systems can improve the production yield of value-added chemicals. The metabolite damage and repair loops are typically not yet included in metabolic reconstructions and it is likely that many remain to be discovered. Here, we review strategies and associated challenges for unveiling non-canonical metabolites and metabolite repair enzymes, including systematic approaches based on high-resolution mass spectrometry, metabolome-wide side-activity prediction, as well as high-throughput substrate and phenotypic screens.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669784 | PMC |
| http://dx.doi.org/10.1016/j.coisb.2021.100379 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis.
Anim Microbiome
January 2025
Department of Large Animal Clinical Sciences, University of Florida, Gainesville, FL, 32610, USA.
Background: Cows that develop metritis experience dysbiosis of their uterine microbiome, where opportunistic pathogens overtake uterine commensals. An effective immune response is critical for maintaining uterine health. Nonetheless, periparturient cows experience immune dysregulation, which seems to be intensified by prepartum over-condition.
View Article and Find Full Text PDFFailure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells.
Cell Mol Biol Lett
January 2025
Enzymology and Metabolism Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4367, Belvaux, Luxembourg.
Background: Metabolism is error prone. For instance, the reduced forms of the central metabolic cofactors nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), can be converted into redox-inactive products, NADHX and NADPHX, through enzymatically catalyzed or spontaneous hydration. The metabolite repair enzymes NAXD and NAXE convert these damaged compounds back to the functional NAD(P)H cofactors.
View Article and Find Full Text PDFEffect of Dietary Ketosis and Nicotinamide Riboside on Hippocampal Krebs Cycle Intermediates and Mitochondrial Energetics in a DNA Repair-Deficient 3xTg/POLβ Alzheimer Disease Mouse Model.
J Neurochem
January 2025
The Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Alzheimer disease is a neurodegenerative pathology-modifying mitochondrial metabolism with energy impairments where the effects of biological sex and DNA repair deficiencies are unclear. We investigated the therapeutic potential of dietary ketosis alone or with supplemental nicotinamide riboside (NR) on hippocampal intermediary metabolism and mitochondrial bioenergetics in older male and female wild-type (Wt) and 3xTgAD-DNA polymerase-β-deficient (3xTg/POLβ) (AD) mice. DNA polymerase-β is a key enzyme in DNA base excision repair (BER) of oxidative damage that may also contribute to mitochondrial DNA repair.
View Article and Find Full Text PDFExploration of the Fasting Hypoglycemic Mechanism of Casein Hydrolysate Enriched with Glu/Gln and Glu/Gln-Containing Peptides in db/db Diabetic-like Mice Using Multiomics Analysis.
J Agric Food Chem
January 2025
School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China.
The fasting hypoglycemic effect of casein hydrolysate (CH) was investigated in db/db diabetic-like mice using a multiomics integrated analysis of peptidome, transcriptome, and metabolome. Results showed that the oral administration of CH at a dose of 600 mg/kg/day for 4 weeks reduced the fasting blood glucose levels by 14.73 ± 9.
View Article and Find Full Text PDFBeyond the Hayflick Limit: How Microbes Influence Cellular Aging.
Ageing Res Rev
January 2025
Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, The Islamic Republic of Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, The Islamic Republic of Iran. Electronic address:
Cellular senescence, a complex biological process resulting in permanent cell-cycle arrest, is central to aging and age-related diseases. A key concept in understanding cellular senescence is the Hayflick Limit, which refers to the limited capacity of normal human cells to divide, after which they become senescent. Senescent cells (SC) accumulate with age, releasing pro-inflammatory and tissue-remodeling factors collectively known as the senescence-associated secretory phenotype (SASP).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!