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Quantification of Propionate
Author(s) -
Doan Mary,
Trefely Sophie,
Xu Jimmy,
Polanco Juan,
Snyder Nathaniel
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.536.3
Subject(s) - propionate , methylmalonic acidemia , metabolism , chemistry , propionic acidemia , catabolism , biochemistry , metabolic pathway , citric acid cycle , metabolomics , propionates , methylmalonic acid , fatty acid metabolism , biology , chromatography , endocrinology , organic chemistry , homocysteine
The metabolism of propionate, a 3‐carbon short chain fatty acid, via propionyl‐CoA to 2‐methyl‐2‐pentenoic acid (2M2PE), a 6‐carbon intermediate, was recently and unexpectedly reported to occur in humans. The enzymology and further metabolism of this pathway remains unclear, but investigations into the metabolism of 2M2PE are an untested avenue in anabolic and catabolic handlings of propionate. To elucidate and quantify this pathway, we employed both targeted and untargeted liquid chromatography‐mass spectrometry. Kinetic and dose response studies in human hepatocellular carcinoma HepG2 cells indicated that 2‐methyl‐2‐pentenoic acid was generated in a propionate‐dependent manner and underwent further metabolism over time. Fibroblasts cells from apparently healthy controls, as well as propionic acidemia and methylmalonic acidemia patients demonstrated similar results confirming this pathway is not dependent on entrance of carbon into the Krebs cycle. In these experiments, surprisingly, simultaneous untargeted metabolomics did not detect any propionate derived metabolites larger than 2M2PE. To extend this work to study human metabolism, we developed a method to quantify propionate and 2M2PE from media, plasma, serum and urine. Support or Funding Information This work was supported by NIH grants R03HD092630 and K22ES026235 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .