Short Chain Dehydrogenase/Reductase Rdhe2 Is a Novel Retinol Dehydrogenase Essential for Frog Embryonic Development

Abstract

Background: Retinoic acid regulates expression of numerous genes, but the enzymes required for its biosynthesis are not fully defined. Results: Rdhe2 oxidizes retinol for retinoic acid biosynthesis, and its down-regulation is lethal for frog embryos. Conclusion: Rdhe2 is a previously unrecognized retinol dehydrogenase required for retinoic acid biosynthesis. Significance: Enzymes homologous to frog rdhe2 may carry out similar functions in other species.

Enzymology of retinoic acid biosynthesis and degradation

“…Proteins encoded by the mouse orthologs of human RDHE2 and RDHE2S genes (SDR16C11 and SDR16C12, respectively) function as all-trans -retinol dehydrogenases in vitro and increase the rate of atRA biosynthesis from retinol when expressed in living cells ( 49,50 ). Whether these two enzymes contribute to atRA biosynthesis during development or adulthood is not yet known, but studies in frogs indicate that the frog ortholog of these enzymes is essential for frog embryonic development ( 50 ). Frogs have a single gene, rdhe2 ( sdr16c90 ), in position orthologous to mouse Rdhe2 ( Sdr16c11 ) and Rdhe2s ( Sdr16c12 ) genes.…”

“…Frogs have a single gene, rdhe2 ( sdr16c90 ), in position orthologous to mouse Rdhe2 ( Sdr16c11 ) and Rdhe2s ( Sdr16c12 ) genes. The enzyme encoded by the frog gene acts as a highly active retinol dehydrogenase that promotes atRA biosynthesis in living cells ( 50 ). Thus, the retinol dehydrogenase activity of RDHE2/RDHE2S enzymes is conserved in lower vertebrates.…”

The Retinol Dehydrogenase Rdh10 Localizes to Lipid Droplets during Acyl Ester Biosynthesis

“…In mammalian cells, Dhrs9 seems to function as a tumor suppressor, consistent with its poor expression in colon cancer cell lines accompanied by insubstantial atRA biosynthesis, relative to normal colon cells (9). In the frog, overexpression of Rdhe2 produces posteriorization defects, similar to those caused by atRA toxicity, whereas substantial knock-down causes embryonic lethality (10). Rdh10 was identified initially as a visual cycle enzyme (11).…”

Human DHRS7, promising enzyme in metabolism of steroids and retinoids?

“…Using the Michaelis-Menten model the following kinetic parameters were calculated: K m = 24.3 mM, V max = 270.3 nmol  min À1  mg À1 ; k cat = 10.22 min À1 , k cat /K m = 410 mM À1  min À1 . The levels of active retinoids are strictly regulated in the organism [36], as altered expression leads to various types of serious damage. This strict regulation is important especially during fetal development.…”