title: Demonstration of a new mammalian isoleucine catabolic pathway yielding an Rseries of metabolites.
abstract: 1. Normal human urine contains small amounts (less than 4 mg/g of creatinine) of 2-ethylhydracrylic acid, formed, we believe, by a previously undisclosed endogenous catabolic pathway for the oxidation of a newly described series of R metabolites of isoleucine. 2. Urinary excretion of 2-ethylhydracrylic acid is variably increased in defects of isoleucine oxidation at distal steps in the catabolic pathway (3-oxoacyl-CoA thiolase deficiency and methylmalonyl-CoA mutase deficiency) and is diminished when proximal steps of the oxidative pathway are blocked as in branched-chain oxo acid decarboxylase deficiency ('maple-syrup-urine' disease). 3. Precursors of R-pathway metabolites [R(-)-2-methylbutyrate and 2-ethylacrylate ] lead to increased 2-ethylhydracrylate excretion in the mammal(rat, rabbit and dog); the corresponding S metabolites [S(+)-2-methylbutyric acid and tiglic acid ], when given in equimolar amounts, have little effect on its excretion, suggesting that little or no interconversion between S and R metabolites occurs in vivo. 4. Studies with 2H-labelled precursors indicate that conversion of R 2-methylbutyrate into 2-ethylhydracrylic acid occurs by a direct pathway (apparently via 2-ethylacrylic acid). 5. The further oxidation of 2-ethylhydracrylic acid to ethylmalonic acid was demonstrated, and may be analogous to S-metabolite oxidation via methyl malonate. 6. Valine metabolites do not interact with the R=isoleucine pathway under the conditions of these experiments in vivo.
mesh_terms: D000179:Acrylates / Q000652:urine; D000818:Animals; D002087:Butyrates / Q000378:metabolism; D004285:Dogs; D005260:Female; D006801:Humans; D006880:Hydroxy Acids / Q000652:urine; D007532:Isoleucine / Q000378:metabolism*; D008297:Male; D008314:Malonates / Q000652:urine; D011817:Rabbits; D051381:Rats; D013997:Time Factors; D014631:Valerates / Q000652:urine
chemical_list: D000179:Acrylates; D002087:Butyrates; D006880:Hydroxy Acids; D008314:Malonates; D014631:Valerates; D007532:Isoleucine; C007674:2-ethylhydracrylic acid