Biosynthesis of retinoic acid from beta-apo-14'-carotenal in ferret on vivo

To determine whether beta-apo-14'-carotenal (an excentric cleavage production of beta-carotene) can serve as a source of intestinally derived retinoic acid, beta-apo-14'-carotenal or retinal in micellar solution was perfused through 60-cm small bowel segments of ferrets in vivo. Both beta-apo-14'-carotenoic acid and retinoic acid were identified in the ferret intestinal mucosa by comparing retention times in HPLC and by ultraviolet/visible spectro. The in vivo perfusion of ferret intestine with 10 mu M beta-14'-carotenal for 2 hr resulted in formation of beta-apo-14'-carotenoic acid (218 +/- 28 pmol/g) and retinoic acid (51 +/- 4 pmol/g). Similarly, a 2-hr intestinal perfusion of 1 mu M 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 int he intestinal mucosa after the perfusion of 1 mu M retinal. However, retinoic acid (30 +/- 3 pmol/g) was still formed form the intestinal perfusion of beta-apo-14'-carotenal with 2 mu M citral. Furthermore, retinol was formed after the intestinal perfusion of beta-apo-14'-carotenal and increased markedly in the presence of citral. This study lends support for an excentric cleavage mechanism in the metabolism of beta-carotene into retinoic acid in vivo. (C) Elsevier Science Inc. 1997.