Biosynthesis of retinoic acid from β-apo-14′-carotenal in ferret in vivo

Abstract

To determine whether β-apo-14′-carotenal (an excentric cleavage product of β-carotene) can serve as a source of intestinally derived retinoic acid, β-apo-14′-carotenal or retinal in micellar solution was perfused through 60-cm small bowel segments of ferrets in vivo. Both β-apo-14′-carotenoic acid and retinoic acid were identified in the ferret intestinal mucosa by comparing retention times in HPLC and by ultraviolet/visible spectra. The in vivo perfusion of ferret intestine with 10 μM β-14′-carotenal for 2 hr resulted in formation of β-apo-14′-carotenoic acid (218 ± 28 pmol/g) and retinoic acid (51 ± 4 pmol/g). Similarly, a 2-hr intestinal perfusion of 1 μM retinal resulted in formation of retinoic acid (30 ± 2 pmol/g). When coperfusing an inhibitor of retinal oxidation, 2 mM citral, retinoic acid was not detected in the intestinal mucosa after the perfusion of 1 μM retinal. However, retinoic acid (30 ± 3 pmol/g) was still formed from the intestinal perfusion of β-apo-14′-carotenal with 2 μM citral. Furthermore, retinol was formed after the intestinal perfusion of β-apo-14′-carotenal and increased markedly in the presence of citral. This study lends support for an excentric cleavage mechanism in the metabolism of β-carotene into retinoic acid in vivo.