Isomerization of all-trans-retinoic acid to 9-cis-retinoic acid.
The discovery of the biological activity of 9-cis-retinoic acid raises questions as to its mode of biosynthesis. A simple mechanism involves the direct isomerization of all-trans-retinoic acid to 9-cis-retinoic acid. It is shown here that bovine liver membranes, but not supernatant fractions, can isomerize all-trans-retinoic acid into 9-cis-retinoic acid and 13-cis-retinoic acid. The concentration of 9-cis-retinoic acid generated approaches its equilibrium concentration, which is determined here to be approximately 15%. However, the isomerization process could not be shown to be saturable, and is first-order in all-trans-retinoic acid in the concentration range measured (8.3 nM to 3 microM). Isomerization reactions measured using bovine liver microsomes appear to be mediated by thiol groups, as they can be blocked by group-specific thiol-blocking reagents such as N-ethylmaleimide. It is interesting to note that the non-stereospecific behaviour observed here mimics what is observed when all-trans-retinoic acid is applied to cells. Finally, significant formation of 9-cis-retinoids was not found when the reaction was carried out with liver microsomes and either all-trans-retinol or all-trans-retinal.
Urbach
J
J
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Rando
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D000818:Animals; D002021:Buffers; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D007536:Isomerism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014212:Tretinoin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
D002021:Buffers; D014212:Tretinoin