ArticleProceedings of the National Academy of Sciences of the United States of America2015
N-lactoyl-amino acids are ubiquitous metabolites that originate from CNDP2-mediated reverse proteolysis of lactate and amino acids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 143 citations in OpenAlex.
- The effect of blood flow restriction training on abdominal visceral fat and plasma N-lactoylphenylalanine among adults with obesity.BMC endocrine disorders · 2026Trial
- Dynamic Metabolic Changes Driven by Exercise Intensity in Acute Swimming.Medicine and science in sports and exercise · 2025Trial
- Exercise intensity determines circulating levels of Lac-Phe and other exerkines: a randomized crossover trial.Metabolomics : Official journal of the Metabolomic Society · 2025Trial
- The effect of blood flow restriction exercise on N-lactoylphenylalanine and appetite regulation in obese adults: a cross-design study.Frontiers in endocrinology · 2023Trial
- Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity.The Journal of clinical investigation · 2021Trial
- Exercise promotes host anti-infection activity through CNDP2 metabolite-mediated inflammasome hyperactivation.PLoS pathogens · 2026Article
- N-Lactoyl amino acids in fermented foods: occurrence, biosynthesis, and flavor enhancement mechanisms.Journal of the science of food and agriculture · 2026Review
- LC-MS/MS quantification of N-lactoyl-phenylalanine and N-lactoyl-tyrosine in human plasma: method validation and clinical application to metformin administration.Translational and clinical pharmacology · 2026Article
- Lactate Biology: Subcellular Routing and Chemical Form Define Function.Biochemistry · 2026Review
- Ketosis elevates plasma concentrations of D-β-hydroxybutyryl-phenylalanine (BHB-Phe) in humans.Nutrition & metabolism · 2026Article
- The blood metabolome of brain health in midlife and influences of genes, microbiome and exposome.Nature aging · 2026Article
- Tissue-dependent enzymatic control of N-acetyl-β-alanine by PTER.The Journal of biological chemistry · 2026Article
- Lactate as a Chemical Modification on Proteins and Metabolites.Annual review of biochemistry · 2026Review
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- Lac-Phe elicits anxiolytic-like effects associated with monoaminergic signaling in mice.Translational psychiatry · 2026Article
- Untargeted metabolomics reveals organism specific biomarkers of carbapenem resistance in Klebsiella pneumoniae and Escherichia coli.NPJ systems biology and applications · 2026Article
- Muscle movement and metabolism: exercise and skeletal muscle as mediators of health-a report from the 26th Annual Harvard Nutrition Obesity Symposium, 2025.The American journal of clinical nutrition · 2026Article
- The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease.Cell death & disease · 2026Article
- Untargeted Metabolomics Identifies N-Lactoyl-Amino Acids as Dose-Responsive Plasma Biomarkers of Metformin Adherence in Type 2 Diabetes.Clinical pharmacology and therapeutics · 2026Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite technological advances in metabolomics, large parts of the human metabolome are still unexplored. In an untargeted metabolomics screen aiming to identify substrates of the orphan transporter ATP-binding cassette subfamily C member 5 (ABCC5), we identified a class of mammalian metabolites, N-lactoyl-amino acids. Using parallel protein fractionation in conjunction with shotgun proteomics on fractions containing N-lactoyl-Phe-forming activity, we unexpectedly found that a protease, cytosolic nonspecific dipeptidase 2 (CNDP2), catalyzes their formation. N-lactoyl-amino acids are ubiquitous pseudodipeptides of lactic acid and amino acids that are rapidly formed by reverse proteolysis, a process previously considered to be negligible in vivo. The plasma levels of these metabolites strongly correlate with plasma levels of lactate and amino acid, as shown by increased levels after physical exercise and in patients with phenylketonuria who suffer from elevated Phe levels. Our approach to identify unknown metabolites and their biosynthesis has general applicability in the further exploration of the human metabolome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.