Retinoic acid, a developmental signal implicated in the formation of the neural axis, is present at high levels in the early embryonic trunk region, where it is synthesized by a novel dehydrogenase. Here we show that the same enzyme is inducible by retinoic acid in P19 teratocarcinoma cells, and we report the cloning from P19 cells of a cDNA encoding a novel dehydrogenase, named retinaldehyde dehydrogenase-2 (RALDH-2). Expression in COS cells shows RALDH-2 to be highly effective in oxidation of retinaldehyde, with no detectable activity on any other aldehyde tested. In situ hybridization histochemistry on the embryonic trunk reveales RALDH-2 mRNA both in mesoderm and neuroectoderm, with highest neuroectodermal expression in the ventral horn of the spinal cord at two restricted locations along the anteroposterior axis, presumably the subpopulation of motoneurons that innervate the limbs.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1996.0015h.x

Molecular Identification of a Major Retinoic-Acid-Synthesizing Enzyme, a Retinaldehyde-Specific Dehydrogenase

A review of recent investigations in the retinoid field is presented. Retinoic acid exerts a prophylactic and a therapeutic effect on chemically induced benign and malignant epithelial tumors in mice. In clinical studies positive therapeutic results have been obtained in patients with preneoplastic and neoplastic epithelial lesions. However, treatment with retinoic acid is limited by serious side effects (hypervitaminosis A syndrome). Therefore, the synthesis of analogs of retinoic acid (retinoids) possessing a more favorable therapeutic ratio has been initiated. Among a large series of synthesized compounds, certain aromatic analogs proved to have a particularly favorable therapeutic ratio. The structure-activity relationship of the most active retinoids is discussed including some biological data concerning prophylaxis and therapy of epithelial tumors. The total synthesis of retinoids according to various building schemes is discussed in detail. Methods for the synthesis of the cyclic end group, of the polyene chain component, and of the full retinoid skeleton are described. Metabolic studies of retinoic acid and of the most active retinoid, as well as the synthesis of some isolated metabolites are outlined. Suggestions concerning the mechanism of action of retinoids are made. Some clinical results on the treatment of acne, psoriasis and precancerous conditions are reported.

Retinoids, a new class of compounds with prophylactic and therapeutic activities in oncology and dermatology

Background
The World Health Organization recommends routine vitamin A supplementation during pregnancy or lactation in areas with endemic vitamin Ad eficiency (where night blindness occurs), based on the expectation that supplementation will improve maternal and newborn outcomes including mortality, morbidity and prevention of anaemia or infection.
Objectives
To review the effects of supplementation of vitamin A, or one of its derivatives, during pregnancy, alone or in combination with other vitamins and micronutrients, on maternal and newborn clinical outcomes.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30March 2015) and reference lists of retrieved studies.
Selection criteria
All randomised or quasi-randomised trials, including cluster-randomised trials, evaluating the effect of vitamin A supplementation in pregnant women.
Data collection and analysis
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
Main results
We reviewed 106 reports of 35 trials, published between 1931 and 2015. We included 19 trials including over 310,000 women,
excluded 15 trials and one is ongoing. Overall, seven trials were judged to be of low risk of bias, three were high risk of bias and for nine it was unclear.

/pdf/vitamin-a-supplementation-during-pregnancy-for-maternal-and-3do0hekhtv.pdf

Vitamin A supplementation during pregnancy for maternal and newborn outcomes

Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid

Biogenesis of retinoic acid from beta-carotene. Differences between the metabolism of beta-carotene and retinal.

Preparation and properties of retinal-oxidizing enzyme from rat intestinal mucosa.

SummaryA Sephadex G-25, batchwise, semimicro, partitioning technique is presented for investigating the binding of retinol to serum components. Rat sera from normal, vitamin A-deficient, and vitamin A-supplemented animals exhibited differences in the binding of retinol. These differences were related to variations in the serum content of vitamin A and protein. The major protein fraction responsible for binding retinol was the α-globulin. Other fractions, namely γ-globulin and albumin, were also capable of binding retinol but to a lesser degree. Human and rat sera exhibited a larger amount of binding for 14C-retinol than for 3H-retinoic acid and 14C-β-carotene. Several unlabeled all-trans derivatives of vitamin A inhibited the binding of 14C-retinol.

David J. Moffa

Papers

Preparation and properties of retinal-oxidizing enzyme from rat intestinal mucosa.

Factors affecting the binding of retinol to serum and its components.