Retinoid metabolism and mode of action.

Vitamin A and its derivaties (retinoids) are necessary for the maintenance of normal phenotypic expression. An attempt at understanding the biochemical role of vitamin A had led to the demonstration of a new pathway for retinol. In this pathway, vitamin A is phosphorylated to retinylphosphate (RP), which is then glycosylated to retinylphosphatemannose (MRP). These two derivatives have been found in a variety of tissues in vivo and in vitro and appear to be ubiquitous components of cellular membranes. The suggestion has been made that MRP may mediate specific cellular interactions by functioning as a lipid intermediate in the biosynthesis of specific glycoconjugates. A study on spontaneously-transformed mouse fibroblasts (Balb/c 3T12-3 cells) has shown that retinoids are active in increasing the adhesive properties of these cells as measured in an EDTA-mediated detachment assay. Various retinoids were tested for their activity in the adhesion test, and this activity was found to correlate well with their biological activity in maintaining the expression of normal epithelial differentiation in other systems. Retinoic acid, 5,6-epoxyretinol, and 5,6-epoxyretinoic acid were the most active compounds. Retinoids without biological activity in other systems were also inactive in inducihg adhesive properties of 3T12-3 cells. Among these were the synthetic derivatives of retinol, anhydroretinol, and 4,5-monoeneperhydroretinol, and the phenyl derivative of retinoic acid. Beta-Ionone, abscisic acid, and juvenile hormone, which are devoid of vitamin A activity in other systems, were also inactive in this system. Retinoid-induced changes in cell surface proteins were investigated but no difference in 125I-fibronectin (MW 220,000) was detectable between retinoid-treated and untreated cells. However, these cells synthesized retinylphosphatemannose and the incorporation of 2-3H-mannose into a specific glycoprotein (gp 180) was found to be enhanced specifically by retinoid treatment. Investigations of the involvement of gp 180 in adhesion are in progress

Retinoid metabolism and mode of action

Vitamin A and its derivatives (retinoids) are necessary for the maintenance of normal phenotypic expression. An attempt at understanding the biochemical role of vitamin A has led to the demonstration of a new pathway for retinol. In this pathway, vitamin A is phosphorylated to retinylphosphate (RP), which is then glycosylated to retinylphosphatemannose (MRP). These two derivatives have been found in a variety of tissues in vivo and in vitro and appear to be ubiquitous components of cellular membranes. The suggestion has been made that MRP may mediate specific cellular interactions by functioning as a lipid intermediate in the biosynthesis of specific glycoconjugates. A study on spontaneously-transformed mouse fibroblasts (Balb/c3T12-3 cells) has shown that retinoids are active in increasing the adhesive properties of these cells as measured in an EDTA-mediated detachment assay. Various retinoids were tested for their activity in the adhesion test, and this activity was found to correlate well with their biological activity in maintaining the expression of normal epithelial differentiation in other systems. Retinoic acid, 5,6-epoxyretinol, and 5,6-epoxyretinoic acid were the most active compounds. Retinoids without biological activity in other systems were also inactive in inducing adhesive properties of 3T12-3 cells. Among these were the synthetic derivatives of retinol, anhydroretinol, and 4,5-monoeneperhydroretinol, and the phenyl derivative of retinoic acid. β-Ionine, abscisic acid, and juvenile hormone, which are devoid of vitamin A activity in other systems, were also inactive in this system. Retinoid-induced changes in cell surface proteins were investigated but no difference in 125I-fibronectin (MW 220,000) was detectable between retinoid-treated and untreated cells. However, these cells synthesized retinylphosphatemannose and the incorporation of 2-3H-mannose into a specific glycoprotein (gp 180) was found to be enhanced specifically by retinoid treatment. Investigations of the involvement of gp 180 in adhesion are in progress

Synthesis of nanocrystalline zeolite beta in supercritical fluids, characterization and catalytic activity

Nanocrystalline zeolite beta with Si/Al ratios 12.5-50 has been synthesized by applying a two-stage varying temperature synthesis and supercritical fluid aided crystallization. Low temperature nucleation of clear aluminosilicate gel and SCF aided crystallization gave quantitative yields of nanocrystalline zeolite beta in shorter crystallization time without the use of alkali cations and seeded gel. The obtained nanocrystalline zeolite beta catalysts are thoroughly characterized by X-ray diffraction, N2 adsorption, 29Si and 27Al MAS NMR, IR spectroscopy and Al incorporation in framework was studied by XPS. These nanocrystalline zeolite beta catalysts displayed good activity and high selectivity towards 4-nitro-o-xylene in the nitration of o-xylene when compared to microcrystalline zeolite beta

Not an Ordinary Killer- Just an Ordinary Guy: When men murder an intimate woman partner

The Murder in Britain Study was designed to examine in detail different types of murder. Using a subset of case files from this study, men who murder other men (MM;n = 424) are compared with men who murder an intimate partner (IP;n = 106) to reflect on the relative conventionality of each group. In terms of many of the characteristics of childhood and adulthood, the IP murder group differs from theMMgroup and appears to be more “ordinary” or “conventional.” However, the IP group is less conventional in that they are more likely to have intimate relationships that had broken down, to have used violence against a previous woman partner as well as against the victim they killed, and to “ specialize” in violence against women

Recent developments in studies on biological functions of vitamin A in normal and transformed tissues

A biochemical pathway of phosphorylation and glycosylation of vitamin A has recently been found in hepatic, intestinal and epidermal tissues. More recent work suggests that mannosylretinylphosphate functions as a donor of mannose to membrane glycoconjugates. These reactions might ultimately explain the effects of vitamin A deficiency and some of the effects of excess vitamin A on biological systems. Studies of the effect of retinoids on cellular in vitro systems showed an increase in the adhesive properties of spontaneously-transformed mouse fibroblasts in culture (Balb/c 3T12-3 cells). These cells are usually detached from the culture gish surface ig an EDTA adhesion assay. After culturing in presence of 3.3 x 10- to 3.3 x 10- M retinol or retinoic acid the cells are no longer lifted from the plate and their morphology and adhesion resemble those of normal fibroblasts. This phenomenon of increased adhesion is observed as early as two days after exposure to the retinoid and it is readily reversible upon culturing in medium without exogenous retinoid. A variety of retinoids was tested in the adhesion assay. The most active compounds were retinol, retinylphosphate, retinoic acid, 5,6-epoxyretinoic acid and the TMMP and DACP derivatives of retinoic acido All these compounds possess biological activity in other systems. Anhydroretinol, perhydromonoeneretinol, the" phenyl derivative of retinoic acid, which do not have biological activity in other systems, did not increase adhesion of 3T12 cells. Other polyprenoid compounds without vitamin A activity were also test ed in this assay. Dolichol, dolichylphosphate juvenile hormone, abscisic aCid, s-ionone, dibutyryl cyclic adenosine monophosphate and sodium butyrate did not induce adhesion. The mechanism by which retinol and retinoic acid increase the adhesive properties of 3T12 cells was investigated. Cyclic adenosine monophosphate and guanosine monophosphate levels were not significantly altered by retino~d treatment at least at 6, 24, 48 and 72 hours after treatment with 3.3 x 10- M retinoic acid, when most30f the cells remain attached. Retinoic acid stimulated the inc~rporation of (2- H) mannose into glycoproteins of 3T12 cells. (11, 12 H and carboxyl-14C)Retinoic acid was incorporated into a compound (Metabolite I) which had chromatographic properties of a glycosylretinylphosphate. The synthesis of this compound was time-dependent and was not carri ed out by formalin -fixed 3T12 cells. Mild alkaline conditiQns which release anhydroretinol from retinylphosphate, also cleaved Metabolite I to yield a product with the polarity of a hydrocarbon, but slightly more polar than anhydroretinol. It is suggested that retinoic atid can be reduced to an alcohol, probably after metabolic modification. It is further suggested that such "reti nol-l i ke" compound woul d fo" ow the same route of phosphoryl at ion and glycosylation as shown for retinol in other systems. Microsomes from 3T12 cells were active as the intact cells in synthesizing mannosylretinylphosphate and dolichyl mannosylphosphate. Exogenous retinylphosphate specifically stimulated the synthesis of mannosylretinylphosphate. Thus it appears that vitamin A is involved in glycosyl transfer reactions in the 3T12 system, as well as in normal membranes. It remains to be established whether the observed increased adhesion is the result of such involvement. A novel reaction for retinol was found in 3T12 cells. Up to 55% of exogenously supplied retinol was converted to the hydrocarbon anhydroretinol in 48 hours. The same reaction was also carried out by microsomes from 3T12 cells, which converted 7% of retinol toanhydroretinol in 30 minutes at 370C. This reaction may well represent a detoxification mechanism for the transformed cell