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Family-wide Annotation of Enzymatic Pathways by Parallel In Vivo Metabolomics.


ABSTRACT: Enzymes catalyze fundamental biochemical reactions that control cellular and organismal homeostasis. Here we present an approach for de novo biochemical pathway discovery across entire mammalian enzyme families using parallel viral transduction in mice and untargeted liquid chromatography-mass spectrometry. Applying this method to the M20 peptidases uncovers both known pathways of amino acid metabolism as well as a previously unknown CNDP2-regulated pathway for threonyl dipeptide catabolism. Ablation of CNDP2 in mice elevates threonyl dipeptides across multiple tissues, establishing the physiologic relevance of our biochemical assignments. Taken together, these data underscore the utility of parallel in vivo metabolomics for the family-wide discovery of enzymatic pathways.

SUBMITTER: Kim JT 

PROVIDER: S-EPMC6874721 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Family-wide Annotation of Enzymatic Pathways by Parallel In Vivo Metabolomics.

Kim Joon T JT   Li Veronica L VL   Terrell Stephanie M SM   Fischer Curt R CR   Long Jonathan Z JZ  

Cell chemical biology 20191003 11


Enzymes catalyze fundamental biochemical reactions that control cellular and organismal homeostasis. Here we present an approach for de novo biochemical pathway discovery across entire mammalian enzyme families using parallel viral transduction in mice and untargeted liquid chromatography-mass spectrometry. Applying this method to the M20 peptidases uncovers both known pathways of amino acid metabolism as well as a previously unknown CNDP2-regulated pathway for threonyl dipeptide catabolism. Abl  ...[more]

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