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A K Lala

Publications and source records attributed to A K Lala.

29 records · Page 2Linked to original sources

Sterol-phospholipid interaction in model membranes: role of C5-C6 double bond in cholesterol.

Several double-bond isomers of cholesterol where the normal C5-C6 double bond (delta 5) has been moved to different positions in the ring skeleton, i.e., delta 1, delta 4, delta 7, delta 8(9), delta 8(14), and delta 14, have been synthesized and incorporated in phosphotidylcholine vesicles. In addition, dienes like delta 5,7, delta 7,14, and delta 8,14 have also been studied. Many of these cholesterol analogues are intermediates in the sterol biosynthesis in different organisms. The incorporation studied indicated that more than 90% of the sterol was present in the vesicles. The effect of these cholesterol analogues was studied by glucose permeability, electron spin resonance, and fluorescence polarization spectroscopy. These studies indicated that delta 14-cholesten-3 beta-ol was most effective in restricting glucose permeability or in increasing the order parameter but was still not as effective as cholesterol. This was followed by delta 8(14)- and delta 8(9)-cholesten-3 beta-ol. The delta 1, delta 4, and delta 7 analogues and the dienols were relatively less effective in condensing the membrane. These studies indicate that the double bond at C5-C6 in cholesterol is most effective for optimal sterol-phospholipid interaction and may have formed the basis of the migration of the double bond from rings C and D in sterols to C5-C6 during the evolution of cholesterol.

Cholesterol↗

The effect of the sterol oxygen function on the interaction with phospholipids.

The effect of cholesteryl ethers (namely cholesteryl methyl ether, cholesteryl ethyl ether, cholesteryl n-propyl ether, cholesteryl isopropyl ether, cholesteryl butyl ether, cholesteryl methoxymethyl ether, cholesteryl (2'-hydroxy)-3-ethyl ether) and cholesteryl ester (namely cholesteryl acetate) is tested on the interaction with phosphatidylcholines in liquid-crystalline and crystalline state. The interfacial properties of sterols are tested at the air-water interface. The cholesteryl ethers show a reduced interfacial stability with increasing hydrophobicity of the ether-linked moiety. The interaction between the sterol derivatives and phospholipids in mixed monolayers is indicated by measuring the deviation from the simple addivity rule (condensing effect). An interaction is found only for cholesteryl (2'-hydroxy)-3-ethyl ether, cholesteryl methyl ether and cholesteryl ethyl ether. These sterols also reduce the glucose permeability of liposomal membranes in this order. In this respect cholesteryl (2'-hydroxy)-3-ethyl ether is as effective as cholesterol. Cholesteryl methyl ether and cholesteryl ethyl ether show 62 and 33 percent of the effect observed with cholesterol. The effect of the sterol derivatives on the gel-to-liquid-crystalline phase transition of dipalmitoylphosphatidylcholine is measured by differential scanning calorimetry. Cholesteryl methyl ether, cholesteryl ethyl ether, and cholesteryl (2'-hydroxy)-3-ethyl ether reduce the energy content of the phase transition nearly as effective as cholesterol, cholesteryl n-propyl ether has only a small effect. Although cholesteryl acetate, and cholesteryl methoxymethyl ether have no condensing or permeability-reducing effect, they have a considerable effect on the gel-to-liquid-crystalline phase transition. Cholesteryl isopropyl ether and cholesteryl butyl ether have no effect. It is concluded that a free 3 beta-hydroxy group is not a prerequisite to observe a sterol-like effect in membranes. However, the interfacial stability and the orientation of the sterol and oxygen moiety at the sterol 3-position are important.

Calorimetry, Differential Scanning↗

On the role of the sterol hydroxyl group in membranes.

The adequacy of sterol derivatives containing a blocked 3-hydroxyl group for sustaining the growth of two sterol auxotrophs has been investigated. Mycoplasma capricolum, a cholesterol-requiring bacterium, grows nearly as well on media supplemented with cholesteryl methyl ether or cholesteryl acetate as on free cholesterol. The two derivatives are recovered unchanged from the bacterial cells. Similarly, cholesteryl methyl ether or ergosteryl methyl ether replace cholesterol or ergosterol as sterol sources for a yeast mutant, strain GL7, defective in 2,3-oxidosqualene-lanosterol cyclization. During aerobic or semianaerobic growth, yeast cells demethylate some of the cholesteryl methyl ether to free cholesterol. However, cells growing on cholesterol methyl ether under strict anaerobic conditions do not produce free sterol. The bearing of these results on the postulated requirement of a free sterol hydroxyl group for membrane function is discussed. Sterol esterification does not appear to be essential for the two microbial systems.

Cell Membrane↗

A proton magnetic resonance study of the conformation of methionine-enkephalin as a function of pH.

It is found that methionine-enkephalin has at least two different conformations in aqueous solution, one at low and one at high pH. From inspection of titration curves and coupling constant values, it seems reasonable to conclude that these conformations are characterized by a folding so as to bring the two ends of the molecule in close proximity. This behavior parallels that found recently in (CD3)2SO as the solvent. It follows that the Phe-Met region of the molecule constitutes a relatively rigid region, but that the chain possesses flexibility around the first Gly residue. Possible implications of this behavior with respect to the receptor site are discussed.

Hydrogen-Ion Concentration↗

Differential effects of cholesterol and lanosterol on artificial membranes.

The effects of cholesterol, 4,4-dimethylcholesterol, and lanosterol (4,4',14alpha-trimethyl-delta8,24-cholestadiene-3beta-ol) on some properties of lecithin vesicles have been compared. Unlike cholesterol, lanosterol retards the exit of trapped glucose from phospholipid vesicles only slightly. The 13C nuclear magnetic resonance spectrum of cholesterol/lecithin vesicles shows no resonances attributable to the sterol. By contrast, several resonances attributable to quaternary carbon atoms or methyl groups are seen in the 13C nuclear magnetic resonance spectrum of lanosterol/lecithin vesicles, indicating that lanosterol is much less immobilized than cholesterol. Because the membrane behavior of 4,4-dimethylcholesterol is closely similar to that of cholesterol, it is concluded that the axial 14-alpha-methyl group is responsible for the lessened membrane immobilization of lanosterol. The results emphasize the importance of a planar sterol alpha-face for interaction with phospholipid acyl chains.

Cholesterol↗

Conformational dependence on pH in tripeptides.

From the 1H-NMR study of Tyr-Gly-Gly and Phe-Gly-Gly in H2O and 2H2O as a function of pH it follows that these tripeptides display at least two and probably three conformational zones. Under slow exchange conditions of the peptidic NH-protons, coupling constants 3J(NH, CaH) may be extracted as the probe. At higher pH values shift values and 3J(a, beta) of the side chain and the titration curves are indicative for these conformational alterations.

Glycine↗

Fluorescence studies on erythrocyte membrane isolated from Plasmodium berghei infected mice.

The erythrocyte host cell plays a key role in the well defined developmental stages of the malarial parasite growth and propogation in the erythrocyte cycle of malaria. The host cell serves the parasites by supplying metabolites and removing the catabolites produced by the obligatory parasites. It has been observed that the plasma membrane of the infected cells show a substantially higher fluidity due to the depletion of cholesterol content from the host cell. The protein component of the membrane is also modulated due to the insertion of new polypeptides of the parasitic origin, which confers upon it new antigenic properties. We have studied the membrane fraction isolated from mice erythrocytes infected with Plasmodium berghei using fluorescent probes like DPH, ANS and series of fluorenyl fatty acids, which permit depth dependent analysis of membrane. We have observed that there is a marked difference in the fluorescence emission wavelength maximum, the dissociation constant Kd of ANS when bound to normal and infected erythrocytes, though relatively small differences are observed in the fluorescence polarisation values of the two cell types. The fluorenyl fatty acids also show the differences when bound to normal and infected erythrocytes, indicating that either they are in a different environment or they have differing binding properties to the two cell types.

Animals↗

Intraoperative enteroscopy in obscure gastrointestinal hemorrhage.

Forty three patients were diagnosed to have obscure gastrointestinal hemorrhage (OGH) between January 1987 and April 1996. Pre-operative diagnostic investigations were useful in localizing the site of bleeding in 28 patients (65.1%). These included small bowel enema (n = 12), erythrocyte tagged scan (n = 8), Meckel's scan (n = 2) and selective visceral angiography (n = 7). Following complete evaluation all patients underwent exploratory laparotomy. At laparotomy 31 patients were found to have gross lesions. Intraoperative enteroscopy (IOE) could detect lesions in 9 of the remaining 12 patients.

Adult↗

Diagnosis and management of gastrointestinal angiodysplasia.

Eighteen patients with gastrointestinal angiodysplasia were seen in a single surgical unit over a period of 8 years. The mean age at onset of symptoms was 33 years. The average duration of symptoms was 54 months (range 2 days-16 years). Three patients had gastric angiodysplasia, two had colonic angiodysplasia, both diagnosed endoscopically preoperatively. The remaining patients required further investigation, which included small bowel enema (SBE), erythrocyte tagged scan (ETC), selective visceral angiography and intraoperative enteroscopy (IOE). SBE was useful but not diagnostic in 3, ETC in 3 and angiography in 5. Four patients required IOE for a diagnosis. Follow up of 17 months is available on all patients. Four had recurrence of symptoms. One required re-exploration and resection of 3 feet of small bowel and right hemicolectomy, another is on hormonal therapy and maintaining normal haemoglobin. Two others are asymptomatic on oral iron therapy.

Adolescent↗