J. Ganguly

On the mechanism of hypocholesterolemic effects of polyunsaturated lipids.

Publisher Summary Cholesteryl esters represent the bulk of the lipids deposited in the aorta during atherosclerosis and an unusual increase in blood cholesterol levels and specific changes in the serum lipoprotein patterns can be directly correlated with the prevalence of coronary artery diseases and of heart attack. Such a causal relationship between elevated plasma cholesterol levels and incidence of atherosclerosis has led to extensive search for effective and safe hypolipidemic agents, and the major efforts of biochemists, clinicians, and pharmacologists have centered on various dietary manipulations and specific drugs. Available information on the hypocholesterolemic effects of polyunsaturated lipids is reviewed; rapidly accumulating evidence suggests that large amounts of cholesterol are eliminated through the bile and feces in animals given polyunsaturated lipids. Because polyunsaturated lipid intake improves the solubility of cholesterol in the bile micelles, such treatments should prevent gallstone formation.

Systemic Mode of Action of Vitamin A

Publisher Summary This chapter reviews the effects of vitamin A deficiency. Vitamin A is essential for several physiological functions in animals—namely, (1) vision, (2) growth, (3) reproduction, and (4) proper maintenance of the integrity of epithelial cells. The chapter also discusses the requirement of vitamin A in specific biological events, such as in the regeneration of the liver cells in an adult rat after partial hepatectomy and in the estrogen-induced development of chick oviduct. The effects of vitamin A deprivation on biosynthesis of RNA and proteins and on glycosylation of proteins are described. The chapter examines the transport, delivery, and mode of action of steroid hormones and the transport and delivery of retinol. An overview of the similarities between the mode of action of retinol and steroid hormones is presented. The chapter concludes that the most pronounced and characteristic effects are invariably on the epithelial cells. It is recognized that one of the typical properties of the epithelial cells is that they undergo constant in situ regeneration. Therefore it follows that vitamin A is required for their controlled division and differentiation. The chapter also focuses on the fact that the steroid hormones circulate in blood bound to proteins, from which they are removed by specific receptor proteins present in the target cells. The steroid–receptor complex in the target cells is translocated into the cell nucleus, where it binds to the chromatin and induces characteristic gene expression.

Effect of unsaturated lipids on the bile flow and biliary excretion of cholesterol and bile salts in rats.

When rats were fed safflower oil or coconut oil for 30 days, or soyalecithin (EPL) or egg phospholipids for 7 days, the rates of bile flow, concentration of cholesterol in the bile as well as unsaturation in the biliary phospholipids were markedly higher in the animals receiving the more unsaturated lipids. It is concluded that feeding of lipids containing polyunsaturated fatty acids effects an increase in the unsaturation of the biliary phospholipids and thereby causes increased excretion of cholesterol through the bile.

High cholesterol diet and esterification of cholesterol by the intestinal mucosa of rats

Young male rats maintained on a diet containing 1% cholesterol were sacrificed at the end of 1st, 2nd, 3rd, 5th, and 7th week. Acetone powders prepared from their intestinal mucosa and pancreas were tested for the synthetic and hydrolytic activities for Vitamin A and cholesterol esters. The esterifying activity of the mucosal enzymes for both Vitamin A and cholesterol increased progressively up to the end of the 5th week; the increase in esterification of cholesterol was more marked with respect to saturated fatty acids, as compared to the unsaturated ones. The pancreatic enzymes remained unaffected. It is suggested that one of the reasons for the accumulation of cholesterol esters in animal tissues may be the increased esterification of the sterol in the mucosa induced by dietary cholesterol.

The mode of absorption of vitamin A across the intestine of rats.

Abstract 1. 1. Stock male rats were starved for 24 hr. and dosed with oily or colloidal solutions of vitamin A alcohol, acetate, or palmitate; 60–90 min. later, the animals were sacrificed and the mucosae, muscles, contents and mesentery of the small intestine, blood, and liver were analyzed. 2. 2. Irrespective of the form fed, vitamin A was present as both ester and alcohol in the contents, mucosae, muscles, and mesentery of the small intestine and in the blood. 3. 3. On feeding the alcohol and the palmitate, no lower fatty acid ester of vitamin A was detectable in any of the samples, all the ester being higher fatty acid ester. Following the feeding of the acetate, the ester part of the intestinal contents was predominantly lower fatty acid ester with appreciable amounts of the higher fatty acid ester, whereas the mucosae contained only small amounts of the former ester, and the intestinal muscles, mesentery, blood, and liver contained none of it.

A simple biosynthetic method for the preparation of glycerol-labelled phosphatidylcholine

A convenient method is described for the preparation of glycerol-labelled phosphatidylcholine with very high specific activity. It involves germination of soybean seeds in the dark at 37°C for 48 h in the presence of labelled glycerol, followed by extraction and purification of the phospholipid.

Fatty acid component of vitamin A ester in sheep liver.

Vitamin A, when extracted along with other lipids from sheep liver, had an E1cm.1% value of 14.4, which was raised to 45.57 on removal of the phospholipids by cold acetone. Selective hydrolysis of triglycerides by an extract of acetone-dried sheep pancreas in the presence of HgCl2 as inhibitor of vitamin A esterase, followed by chromatography through alumina gave a product with E1cm.1% value of 276. This on chromatography through magnesium oxide raised the E1cm.1, value to 601.5, representing 64% pure vitamin A ester calculated as palmitate, and the total recovery was 23% of the starting oil. The purified ester preparation, when subjected to reverse-phase chromatography on silicone-impregnated paper, gave a single ultraviolet fluorescent band. The fluorescent band on hydrolysis gave only one fatty acid. This was conclusively identified to be palmitic acid.

Uptake, during Absorption, of Free Fatty Acids by Phospholipids of the Intestinal Mucosa of Rats

SEVERAL authors have suggested that the phospholipids may participate in the absorption of fats1–3. However, an examination of the 32P turnover in the phospholipids of the mucosa of dogs and rats led Zilversmit et al.4,5 to conclude that these compounds are of little significance in this process. More recently, from the results of 32P-turn-over in experiments with everted intestinal sacs of golden hamsters, Johnston and Bearden6 have suggested that the phosphatidic acid might be an intermediate in the transport of fatty acids during absorption. But these claims could not be confirmed by Gurr et al.7, who studied the 32P turnover of the intestinal phospholipids of living rats. It is clear that in all these experiments labelled 32P was used and no attempt was made to investigate the uptake of free fatty acids by the mucosal phospholipids; we have found that the mucosal phospholipids rapidly take up the free fatty acid from the lumen of the small intestine.

Purification of a retinol binding protein from the hen-oviduct cytosol and its immunological cross-reactivity with those from the nucleus

Cellular retinol-binding protein was purified from the cytosol of the oviducts of laying hens by ammonium sulphate fractionation and chromatography on Sephadex G-75 and DEAE-Sephadex A-50 columns. Analysis of the purified retinol-binding protein on 10% SDS-polyacrylamide gel revealed the presence of a doublet representing very similar molecular sizes. Antiserum was prepared against the purified cellular retinol-binding protein, and on the basis of (a) immunodiffusion test and (b) immunoneutralization of 3H-labelled retinol-cellular retinol-binding protein complex on a column of Sephadex G-75, the antiserum appeared to be specific. The antiserum showed cross-reactivity with the nucleosol and a 0.4 M NaCl extract of the chromatin of the oviduct nuclei, while it did not react with the major egg-white proteins such as ovalbumin, conalbumin and ovomucoid.