Identities and differences in the metabolism of tocotrienols and tocopherols in HepG2 cells

Abstract

The metabolism of α- and γ-tocotrienol was investigated in HepG2 cells. Metabolites were identified by HPLC and gas chromatography/mass spectrometry. γ-Tocotrienol was degraded to γ-CEHC (carboxyethyl hydroxychroman), γ-CMBHC (carboxymethylbutyl hydroxychroman), γ-CMHenHC (carboxymethylhexenyl hydroxychroman), γ-CDMOenHC (carboxydimethyloctenyl hydroxychroman) and γ-CDMD(en)2HC (carboxydimethyldecadienyl hydroxychroman). α-Tocotrienol yielded α-CEHC, α-CMBHC, α-CMHenHC and α-CDMOenHC, whereas α-CDMD(en)2HC could not be detected. These findings demonstrate that the trienols are metabolized essentially like tocopherols, i.e., by ω-oxidation followed by β-oxidation of the side chain. The failure to detect CMBHC with the original double bond in the side chain reveals that auxiliary enzymes are involved, as in the metabolism of unsaturated fatty acids. CMBHC were the most abundant metabolites obtained from the tocotrienols as well as from α-tocopherol. Quantitatively, the tocotrienols were degraded to a larger extent than their counterparts with saturated side chains. The pronounced quantitative differences in the metabolism between individual tocopherols as well as between tocotrienols and tocopherols in vitro suggest a corresponding lack of equivalence in vivo.