Alloisoleucine differentiates the branched-chain aminoacidemia of Zucker and dietary obese rats.
Bottom Line: This elevation was greater than that of other BCAAs (107-124%).Cytotoxic branched-chain ketoacids (BCKAs) accumulate in genetic disorders affecting BCKDC.BCKAs increase reactive oxygen species, stress kinase activation, and mitochondrial dysfunction.
Affiliation: Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania, USA.Show MeSH
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Mentions: BCAAs, Phe and alloisoleucine were measured in plasma by UPLC-MS. Compared to lean rats, obesity elevated BCAAs by 107–124% on average in plasma from obese Zucker rats (lean vs obese: Ile, 42 ± 3 vs 87 ± 3 μM; Leu, 85 ± 5 vs 190 ± 10 μM; Val, 125 ± 7 vs 266 ± 9 μM; n=9/group, p<0.001). Phenylalanine was elevated 24% (67 ± 1 vs 83 ± 2 μM, p<0.001). Alloisoleucine is the R-epimer of Ile, formed as a rare side reaction during the reversible transamination of Ile or S-ketomethlyvalerate (S-KMV) 20. The mechanism of its formation is schematically shown in Fig 1. In obese Zucker rats, alloisoleucine was elevated 238% (Fig 2A), with some individual values between 1.3 and 1.8 μM (not shown). No significant correlation was observed between plasma Ile and alloisoleucine concentrations in either lean or obese rats (data not shown).
Affiliation: Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania, USA.