Biomedical subjects

P V Subbaiah

Publications and source records attributed to P V Subbaiah.

At least 37 records · Page 2Linked to original sources

PubMed1994

Hydrolysis and transesterification of platelet-activating factor by lecithin-cholesterol acyltransferase.

Purified lecithin-cholesterol acyltransferase (LCAT, EC 2.3.1.43) from human plasma was found to hydrolyze platelet-activating factor (PAF) to lyso-PAF and acetate. In addition, it catalyzed the transfer of the acetate group from PAF to lysophosphatidylcholine, forming lyso-PAF and a 1-acyl analog of PAF. In contrast to the cholesterol-esterification reaction carried out by the enzyme, the hydrolysis and transacetylation of PAF by LCAT did not require an apoprotein activator and were not inhibited by sulfhydryl inhibitors but were inhibited by serum albumin. When added to a proteoliposome substrate of LCAT or to whole plasma, PAF inhibited cholesterol esterification by LCAT competitively. PAF acetylhydrolase (EC 3.1.1.47), purified from human plasma, also catalyzed the transfer of acetate from PAF to lysophosphatidylcholine. However, the LCAT-catalyzed reactions of PAF were not due to contamination with PAF acetylhydrolase, since the ratio of acetyl transfer to acetyl hydrolysis was 3 times greater for LCAT, when compared with PAF acetylhydrolase under identical conditions. Furthermore, recombinant human LCAT secreted by baby hamster kidney cells also catalyzed the hydrolysis and transacetylation of PAF. These results demonstrate that LCAT can inactivate PAF in plasma by transacetylation and suggest that it may have a role in the metabolism of PAF, and possibly of oxidized phospholipids, in plasma.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1994

Diverse effects of essential (n-6 and n-3) fatty acids on cultured cells.

Fatty acids (FAs) have long been recognized for their nutritional value in the absence of glucose, and as necessary components of cell membranes. However, FAs have other effects on cells that may be less familiar. Polyunsaturated FAs of dietary origin (n-6 and n-3) cannot be synthesized by mammals, and are termed 'essential' because they are required for the optimal biologic function of specialized cells and tissues. However, they do not appear to be necessary for normal growth and metabolism of a variety of cells in culture. The essential fatty acids (EFAs) have received increased attention in recent years due to their presumed involvement in cardiovascular disorders and in cancers of the breast, pancreas, colon and prostate. Many in vitro systems have emerged which either examine the role of EFAs in human disease directly, or utilize EFAs to mimic the in vivo cellular environment. The effects of EFAs on cells are both direct and indirect. As components of membrane phospholipids, and due to their varying structural and physical properties, EFAs can alter membrane fluidity, at least in the local environment, and affect any process that is mediated via the membrane. EFAs containing 20 carbons and at least three double bonds can be enzymatically converted to eicosanoid hormones, which play important roles in a variety of physiological and pathological processes. Alternatively, EFAs released into cells from phospholipids can act as second messengers that activate protein kinase C. Furthermore, susceptibility to oxidative damage increases with the degree of unsaturation, a complication that merits consideration because lipid peroxidation can lead to a variety of substances with toxic and mutagenic properties. The effects of EFAs on cultured cells are illustrated using the responses of normal and tumor human mammary epithelial cells. A thorough evaluation of EFA effects on commercially important cells could be used to advantage in the biotechnology industry by identifying EFA supplements that lead to improved cell growth and/or productivity.

Animals↗

PubMed1994

Differential effects of eicosapentaenoic acid and docosahexaenoic acid on human skin fibroblasts.

To better understand the mode of action of omega 3 fatty acids in cell membranes, human foreskin fibroblasts were grown in serum-free medium supplemented with 50 microM oleic acid linoleic acid, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), and the effects on membrane composition, fluorescence polarization and enzyme activities were followed. The cells were enriched with EPA and DHA up to 7 and 13% of total lipids, respectively, of which > 95% was associated with phospholipids. In addition, the concentration of 22:5n-3 increased with both EPA and DHA to 7.5, and 2.1% of the total fatty acids, respectively. When compared to controls (oleic acid), cells treated with DHA showed a decrease in cholesterol, phospholipids, arachidonic acid (AA) and free cholesterol/phospholipid ratio (P < 0.05). In the presence of EPA, only decreases in AA and cholesterol were significant (P < 0.05). Membrane fluidity, assessed by fluorescence anisotropy, was increased 16% in cells enriched with DHA (P < 0.05), but showed no change with EPA or linoleic acid. There was an increase in membrane-associated 5'-nucleotidase (+27%) and adenylate cyclase (+19%) activities (P < 0.05), in DHA-enriched, but not in EPA-enriched cells, when compared with oleate controls. The studies show that incorporation of DHA, but not EPA, into cell membranes of fibroblasts alters membrane biophysical characteristics and function. We suggest that these two major n-3 fatty acids of fish oils have differential effects on cell membranes, and this may be related to the known differences in their physiological effects.

5'-Nucleotidase↗

PubMed1994

Abnormal acyltransferase activities and accelerated cholesteryl ester transfer in patients with nephrotic syndrome.

To determine the effects of the nephrotic syndrome (NS) on atherogenic risk, we studied the lipoprotein composition and the activities of lecithin-cholesterol acyltransferase (LCAT), lysolecithin acyltransferase (LAT), and cholesteryl ester transfer (CET) in the plasma of 11 NS patients and 10 control subjects. NS plasma had lower ratios of high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and HDL2/HDL3 and an elevated free cholesterol (FC) to phosphatidyl choline (PC) ratio (1.09 +/- 0.27 in NS and 0.72 +/- 0.21 in controls, P < .02), all of which indicate an increased atherogenic potential. LCAT activity was normal in NS plasma when assayed with an exogenous substrate, but was 40% lower than in control plasma when assayed with the endogenous substrates. However, in vitro addition of serum albumin to NS plasma failed to normalize the LCAT activity. The LAT reaction, which is catalyzed by LCAT protein in the presence of LDL, was 60% to 80% higher in NS plasma, and consequently the ratio of LAT/LCAT activities was increased twofold. CET activity was significantly increased (+160% of control), and this abnormality was attributable to changes in both the acceptor (very-low-density lipoprotein [VLDL] + LDL) and donor (HDL) lipoproteins and possibly in CET protein. These results suggest that the NS may increase the risk of atherosclerosis not only by adversely affecting the concentrations of lipoproteins, but also by altering their composition and function.

1-Acylglycerophosphocholine O-Acyltransferase↗

PubMed1994

n-3 and n-6 fatty acid processing and growth effects in neoplastic and non-cancerous human mammary epithelial cell lines.

The type rather than the amount of dietary fat may be more important in breast carcinogenesis. While animal studies support this view, little is known about the effects of essential fatty acids (EFAs) at the cellular level. The MCF-7 breast cancer and the MCF-10A non-cancerous human mammary epithelial cell lines are compared in terms of growth response to EFAs and ability to incorporate and process the EFAs. Eicosapentaenoic (EPA, n-3) and docosahexaenoic (DHA, n-3) acids, presented bound to albumin, inhibited the growth of MCF-7 cells by as much as 50% in a dose-dependent manner (6-30 microM) in medium containing 0.5% serum. alpha-Linolenic (LNA, n-3) and arachidonic (AA, n-6) acids inhibited growth less extensively, while linoleic acid (LA, n-6) had no effect. In contrast, MCF-10A cells were not inhibited by any of the EFAs at levels below 24 microM. The differential effects of AA, EPA and DHA on MCF-7 and MCF-10A cells support a protective role of highly unsaturated essential fatty acids against breast cancer. The EFAs were primarily incorporated into phosphoglycerides. MCF-7 cells showed chain elongations and possibly delta 8 desaturation, but no AA was formed from LA, nor EPA or DHA from LNA. In contrast, MCF-10A cells desaturated and elongated the exogenous EFAs via all the known pathways. These findings suggest defects in the desaturating enzymes of MCF-7 cells. LNA, DHA and AA presented to MCF-7 cells in phospholipid liposomes inhibited growth as extensively as albumin-bound free acids, but were less extensively incorporated, suggesting different mechanisms of inhibition for the two methods.

Breast↗

PubMed1993

Role of sphingomyelin in the regulation of cholesterol esterification in the plasma lipoproteins. Inhibition of lecithin-cholesterol acyltransferase reaction.

In order to determine whether sphingomyelin (SPH) affects the rate of cholesterol esterification by plasma lecithin-cholesterol acyltransferase (LCAT), we studied the effects of its incorporation in to defined proteoliposome substrates containing phosphatidyl choline (PC), unesterified cholesterol, and apoprotein A-I, on the activity of purified LCAT. Cholesterol esterification was inhibited by up to 90% in the presence of SPH, and this inhibition was reversed by treatment with bacterial sphingomyelinase. The inhibition could be overcome by increasing the concentration of PC, but not unesterified cholesterol or apoprotein A-I, in the substrate. The effect of SPH was not related to the alterations in the size of the substrate particle and was not dependent on the type of acyl donor or apoprotein activator employed. The lysolecithin acyltransferase and phospholipase reactions carried out by LCAT were also inhibited by SPH. Kinetic studies suggested that: 1) LCAT binds better to substrate vesicles which contain SPH; 2) SPH competes with PC in binding to the active site of the enzyme; and 3) SPH is a more powerful competitive inhibitor than a diether analog of PC. The ability of various lipoproteins to act as substrates for purified LCAT varied inversely with the SPH/PC ratio. Treatment of the lipoproteins with sphingomyelinase activated the LCAT reaction, the percent activation being directly proportional to the SPH concentration in the native lipoprotein. Enrichment of high density lipoproteins with SPH inhibited cholesterol esterification in them by 50%, and this inhibition could be reversed by the degradation of SPH. These results show that SPH is a physiological inhibitor of cholesterol esterification in the plasma, by virtue of its competition with PC, the acyl donor for the reaction.

Apolipoprotein A-I↗

PubMed1993

Activation of plasma lysolecithin acyltransferase reaction by apolipoproteins A-I, C-I and E.

The lysolecithin acyltransferase (LAT) activity of lecithin-cholesterol acyltransferase (LCAT) converts lysophosphatidylcholine (lyso PC) to PC, and requires low-density lipoproteins (LDL). To determine whether LDL can be replaced by defined substrates, we tested proteoliposomes containing egg PC, labeled lyso PC and apoprotein (apo) A-I at molar ratios of 250:12.5:0.8, as substrate for purified enzyme. A significant percent of lyso PC in this substrate was acylated to PC, indicating that apo A-I can substitute for apo B in LAT reaction, and that PC is the acyl donor in the reaction. Apo C-I and apo E were, respectively, 70% and 40% as effective as apo A-I. When both lyso PC and free cholesterol (FC) were incorporated into the same proteoliposome, they competed with each other for the acyl groups, with 72% of the total acylation being directed to FC and 28% to lyso PC, at equimolar concentrations. With the native lipoproteins, the esterification of lyso PC was dominant in LDL, whereas FC esterification was dominant in high-density lipoproteins (HDL). Albumin inhibited LAT and activated LCAT in both lipoproteins, but its effects were more pronounced in HDL. These results indicate that the esterification of lyso PC and FC involve the same mechanism, and that the relative predominance of LAT on LDL is due to higher affinity of lyso PC to LDL, compared to HDL.

1-Acylglycerophosphocholine O-Acyltransferase↗

PubMed1993

Accelerated cholesteryl ester transfer in noninsulin-dependent diabetes mellitus.

Alterations in core lipid composition of lipoproteins in noninsulin-dependent diabetes mellitus (NIDDM) patients have suggested that the heteroexchange of neutral lipids between HDL and the apo B-containing lipoproteins may be enhanced. For this reason, we studied cholesteryl ester transfer (CET) in ten sulfonylurea-treated patients with stable NIDDM. CET measured in all NIDDM subjects with an assay of mass transfer was significantly greater than that of controls at 1 and 2 h (P < 0.001); the transfer of radiolabeled CE also was increased in a subset of four of the NIDDM group (NIDDM k = 0.21 +/- 0.04 vs. control k = 0.10 +/- 0.05; P < 0.05). A weak correlation was demonstrable between the mass of CE transferred at 1 h and diabetic control expressed as plasma fructosamine (r = 0.58, P < 0.09). To characterize this disturbance in CET further, the donor (HDL + VHDL) and acceptor (VLDL + LDL) lipoprotein fractions were isolated by ultracentrifugation at d 1.063 g/ml from NIDDM and control plasma and a series of recombination experiments were performed. Combining NIDDM acceptor with control donor fractions that contained HDL and CETP and not the combination of NIDDM donor and control acceptor lipoproteins resulted in an accelerated CET response identical to that observed in NIDDM whole plasma. This observation indicated that the abnormality in CET in NIDDM was associated with the VLDL + LDL fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗

PubMed1993

Incorporation of dietary n-3 fatty acids into molecular species of phosphatidyl choline and cholesteryl ester in normal human plasma.

To understand the differences in the antiatherogenic actions of eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6), we determined their incorporation into molecular species of phosphatidylcholine (PC) and cholesteryl ester (CE) after feeding 12 g marine lipid concentrate/d to six normolipidemic males for 28 d. The time course of incorporation of EPA into plasma PC and CE showed a precursor-product relationship. In contrast, the DHA concentration of CE was markedly lower than that in PC, and the EPA-DHA ratio was 2-6-fold higher in CE than in PC at all time intervals. Three PC species--16:0-20:5, 16:0-22:6, and 18:0-20:5--increased, whereas 18:1-18:2, 18:0-18:2, and 16:0-20:3 decreased. In vitro formation of CE species in plasma by lecithin-cholesterol acyltransferase (LCAT) showed an increased formation of 20:5 CE but not 22:6 CE, indicating that DHA is a poor substrate for LCAT. These results demonstrate a differential incorporation of EPA and DHA into plasma lipids, which may be related to the differences in their biological effects.

Adult↗

PubMed1992

Altered positional specificity of human plasma lecithin-cholesterol acyltransferase in the presence of sn-2 arachidonoyl phosphatidyl cholines. Mechanism of formation of saturated cholesteryl esters.

The positional specificity of purified human lecithin-cholesterol acyltransferase (LCAT) was studied by analyzing the labeled cholesteryl ester (CE) species formed in the presence of proteoliposome substrates containing mixed chain phosphatidylcholine (PC) species, labeled cholesterol and apoprotein A-I. Whereas over 90% of the acyl groups used for CE synthesis were derived from the sn-2 position of most of the naturally occurring PC substrates, about 75% of the CE species formed in the presence of sn-1-myristoyl 2-arachidonoyl PC, sn-1-palmitoyl-2-arachidonoyl (PAPC) and sn-1-palmitoyl 2-docosahexaenoyl PC were derived from the sn-1-position. On the other hand, rat LCAT utilized mostly sn-2-acyl group from either PAPC or from sn-1-palmitoyl 2-linoleoyl PC. The positional specificity of the human enzyme was not affected by the alteration in the matrix fluidity, type of the apoprotein activator used, or by the free cholesterol/PC ratio in the substrate. These results show that the positional specificity of human plasma LCAT is altered in the presence of sn-2-arachidonoyl PC, or sn-2-docosahexaenoyl PC, probably due to steric restrictions at the active site, and this may account for the formation of disproportionately high concentrations of saturated CE, and low concentrations of long-chain polyunsaturated CE in human plasma, relative to the composition of sn-2-acyl groups in plasma PC.

Animals↗

PubMed1992

Effect of apoprotein B conformation on the activation of lysolecithin acyltransferase and lecithin: cholesterol acyltransferase. Studies with subfractions of low density lipoproteins.

In order to determine the role of apoprotein (apo) B conformation in the activation of the lysolecithin acyl-transferase reaction, we studied the activation of purified enzyme by various subfractions of low density lipoprotein (LDL), isolated by density gradient centrifugation. The activation of LAT correlated positively with the density of LDL and negatively with cholesterol/protein and triglyceride (TG)/protein ratios. The enzyme activation was also positively correlated with the number of trinitrobenzenesulfonic acid-reactive lysine amino groups, which increased with increasing density of LDL. The immunoaffinity of the LDL subfractions for B1B6, a monoclonal antibody directed to the receptor-binding region of apoB, increased with increasing density, while the affinity toward C1.4, a monoclonal antibody directed to the amino-terminal region of apoB, was not altered. Enrichment of normal whole LDL with TG resulted in a 45% reduction in enzyme activation, a 27% decrease in the number of trinitrobenzenesulfonic acid-reactive lysine groups, and a marked reduction in the immunoaffinity for B1B6. All these parameters reversed to normal when the TG-enriched LDL was treated with milk lipoprotein lipase, which specifically reduced the TG content of LDL. The LDL subfractions also supported cholesterol esterification by the purified enzyme, in parallel with lysolecithin esterification, indicating that apoB can also serve as an activator of the lecithin-cholesterol acyltransferase reaction. These results strongly suggest that the localized conformational change of apoB which occurs during the TG depletion of the precursor particle is critical for its activation of acyltransferase reactions, in a manner analogous to its interaction with the cellular receptors.

1-Acylglycerophosphocholine O-Acyltransferase↗

PubMed1992

Effect of marine lipids on cholesteryl ester transfer and lipoprotein composition in patients with hypercholesterolemia.

While the effects of omega-3 (n-3) fatty acids present in marine lipids on plasma lipoprotein levels have been intensively studied, less is known about their impact on reverse cholesterol transport. For this reason, for a 3-month period we studied the effects of the administration of n-3 fatty acids (6 g/day) as a dietary supplement on cholesteryl ester transfer (CET), a key step in this process, and lipoprotein composition in 12 outpatients with genetically heterogeneous forms of hypercholesterolemia. Before treatment, CET in hypercholesterolemic patients, estimated as the mass of cholesteryl ester (CE) transferred from high density lipoprotein (HDL) to very low density lipoprotein (VLDL) plus low density lipoprotein (LDL), was markedly accelerated, peaking after only 1-2 hours of incubation of whole plasma; this response differed significantly (p < 0.001) from the initial delayed curvilinear response of control subjects. Consistent with the accelerated CET occurring in vivo, their triglyceride to esterified cholesterol core lipid ratio before treatment was reduced in the intact VLDL fraction and VLDL1 but not in VLDL2 or VLDL3 and was reciprocally increased in HDL. In addition, the free (unesterified) cholesterol to lecithin ratio of VLDL1 was abnormally increased. Recombination experiments performed with individual lipoprotein fractions revealed that accelerated CET was specifically associated with the VLDL1 subfraction and not LDL, HDL, and cholesteryl ester transfer protein (CETP), although pretreatment levels of CETP were significantly increased (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Accelerated cholesteryl ester transfer in patients with insulin-dependent diabetes mellitus.

Abnormalities in cholesteryl ester transfer (CET) may play a role in the development of diabetic arterial vascular complications. To assess this important step systematically in reverse cholesterol transport, we have studied 20 treated, clinically stable, normolipidaemic patients. Contrary to the impairment in CET described previously in NIDDM, the mass of CE transferred from HDL to VLDL + LDL was significantly greater in IDDM patients than in controls at 1,2, and 4 h (P less than 0.001). When the d less than 1.063 plasma fractions from IDDM subjects were combined with controls d less than 1.063 fractions, an accelerated CET response was observed which was identical to that found in intact IDDM plasma. This finding, which indicates that this disturbance in CET was associated with the acceptor lipoproteins, was confirmed when we found that it was reproduced by the addition of IDDM VLDL and not LDL to control d greater than 1.063 fractions. Changes observed in lipoprotein core lipid composition were consistent with accelerated CET occurring in IDDM in vivo: the TG/CE core lipid ratio was decreased in VLDL from six subjects (diabetic 9.5 +/- 0.8 vs control 12.9 +/- 3.4; P less than 0.1) and increased in their HDL (diabetic 0.55 +/- 0.11 vs control 0.42 +/- 0.04; P less than 0.025). No correlation was demonstrable between estimates of diabetic control (glycoalbumin, fasting glucose) and CET. These data indicate that CET may be abnormally increased in normolipidaemic IDDM patients. A defect of this type may be atherogenic because it increases the number of lipoprotein particles in plasma which resemble cholesteryl ester-enriched chylomicron and VLDL remnants but whose normal receptor-mediated catabolism may be altered.

Adult↗

PubMed1991

Accelerated cholesteryl ester transfer in plasma of patients with hypercholesterolemia.

To discern the mechanism(s) that underlie abnormal cholesteryl ester transfer (CET) in patients with hypercholesterolemia, we have studied this dysfunctional step in reverse cholesterol transport in 13 subjects with genetically heterogeneous forms of hypercholesterolemia (HC). In all HC patients, the mass of CE transferred in whole plasma from HDL to VLDL and LDL increased rapidly initially and was significantly greater than in controls at 1, 2, and 4 h (P less than 0.005). To further characterize this disturbance, we performed a series of recombination experiments. Combining HC d less than 1.063 containing acceptor VLDL + LDL with the d greater than 1.063 fraction from controls containing donor HDL + CE-transfer protein (CETP) and not the converse combination showed the same characteristics of accelerated CET noted with intact HC plasma, indicating that abnormal transfer was associated with the HC acceptor lipoproteins. When HC VLDL and its subfractions and LDL were isolated separately and then combined with control d greater than 1.063 fractions, accelerated CET was only associated with VLDL1. Consistent with an acceleration of the neutral lipid transfer reaction occurring between HDL and VLDL1 in HC in vivo, we found that the triglyceride/CE ratio was decreased in HC VLDL1 (P less than 0.001), and increased in HDL (P less than 0.25). CETP mass was significantly increased in HC plasma (HC 2.3 +/- 4 micrograms/ml vs. control 1.3 +/- 0.3 micrograms/ml; mean +/- SD; P less than 0.025). This series of observations demonstrate that CET is accelerated in the plasma of HC patients, and this disturbance results from dysfunction of the VLDL1 subfraction rather than an elevation of CETP levels. Since an abnormality of this type in vivo can lead to the accumulation of potentially atherogenic CE-enriched apoB-containing lipoproteins in plasma, it may be an additional previously unrecognized factor that increases cardiovascular risk in HC patients.

Apolipoproteins B↗

PubMed1991

Effects of estropipate treatment on plasma lipids and lipoprotein lipid composition in postmenopausal women.

It is generally believed that the cardioprotective benefit of long term treatment of postmenopausal women with estrogen results in part from its capacity to increase high density lipoprotein (HDL) and lower low density lipoprotein (LDL) concentrations. The extent to which the various estrogens employed in replacement treatment affect the composition of lipoproteins, however, is not known. For this reason, we have examined the impact of one such preparation, the synthetic estrone estropipate (1.25 mg/day), on lipoprotein levels and composition in six postmenopausal women. After 6 months of treatment, whole plasma triglyceride (pretreatment, 135 +/- 63; posttreatment, 143 +/- 56 mg/dL), cholesterol (pretreatment, 232 +/- 14; posttreatment, 216 +/- 29 mg/dL), and HDL-C (pretreatment, 57.8 +/- 14.8; posttreatment, 55.6 +/- 13.2) were unchanged. However, plasma free (unesterified) cholesterol (FC) fell (pretreatment, 73.4 +/- 6.2; posttreatment, 53.7 +/- 9.3 mg/dL; P less than 0.05) and lecithin (L) rose significantly (pretreatment, 2.12 +/- 0.29; posttreatment, 2.47 +/- 0.34 mumol/mL; P less than 0.01). The consequence of these changes was a significant decline in the plasma FC/L ratio (pretreatment, 0.91 +/- 0.17; posttreatment, 0.68 +/- 0.12; P less than 0.01) to levels observed in healthy menstruating women. The calculated lipoprotein particle size was unchanged in very low density lipoproteins and increased significantly (P less than 0.05) in LDL after estropipate therapy. Since qualitatively altered lipoproteins enriched in FC and an increased FC/L ratio in plasma are both associated with increased coronary risk, the improvement noted in these parameters after estropipate therapy indicates that its use may be beneficial despite the lack of change in whole plasma lipids.

Cholesterol↗

PubMed1991

Effect of apolipoprotein activators on the specificity of lecithin:cholesterol acyltransferase: determination of cholesteryl esters formed in A-I/C-III deficiency.

Although it is known that plasma lecithin:cholesterol acyltransferase (LCAT) is activated by several apolipoproteins (apo) including A-I, C-I, D, A-IV, and E, it is not clear what the physiological importance of having different apolipoprotein activators is. One possible explanation is that the activation by different apolipoproteins may result in the utilization of different species of phosphatidylcholine (PC), leading to the formation of different species of cholesteryl esters (CE). In order to determine this possibility, we analyzed the molecular species composition of PC and CE in two patients with familial deficiency of apoA-I and apoC-III. The LCAT activity, assayed by three different procedures, was found to be 36-63% of the control value. The lower LCAT activity, however, was due to deficiency of the enzyme rather than the absence of apoA-I. The patients' plasma was relatively enriched with sn-2 18:2 PC species reflecting the partial deficiency of LCAT activity. The fatty acid composition of plasma CE was not significantly different from that of controls. HPLC analysis of labeled CE formed after incubation of plasma with [C14]cholesterol showed no significant difference in the species of CE synthesized by the LCAT reaction. The transfer of pre-existing as well as newly formed CE from HDL to the apoB-containing lipoproteins was accelerated compared to control plasma. These results show that the absence of apoA-I does not significantly affect either the activity or the specificity of LCAT, and that the other apolipoprotein activators can substitute adequately for it.

Adult↗

PubMed1991

Lipoprotein composition and HDL particle size distribution in women with non-insulin-dependent diabetes mellitus and the effects of probucol treatment.

To further characterize the spectrum of potentially atherogenic disturbances in lipoprotein composition in non-insulin-dependent diabetes mellitus (NIDDM), we have studied a subset of women with NIDDM before and after treatment with the lipophilic lipid-lowering drug probucol (1 gm day), which we have shown corrects certain compositional abnormalities these women share with subjects who have hypercholesterolemia. Before treatment, the NIDDM group had a somewhat higher plasma triglyceride level (154 +/- 58.3 mg/dl, vs control, 80.0 +/- 21 mg/dl [mean +/- SD]; p less than 0.025) than controls but their cholesterol and high-density lipoprotein cholesterol (HDL-C) levels did not differ from control levels. A number of significant disturbances, however, were present in the surface and core lipid composition of their lipoproteins. Although the cholesterol content of NIDDM low-density lipoprotein (LDL) was similar to that of controls, its content of sphingomyelin and phosphatidylinositol plus phosphatidylserine and sphingomyelin-to-lecithin ratio all were significantly reduced. Moreover, their very-low-density lipoprotein (VLDL) and HDL2 tended to have reduced amounts of free (unesterified) cholesterol (FC) relative to lecithin, and their HDL2 and HDL3 tended to be triglyceride enriched. Probucol therapy resulted in significant decreases in total plasma cholesterol (-15%), FC (-28%), HDL-C (-22%), and triglyceride (-16%) and in apoproteins A-I, B, and E (apo A-I, B, and E), without changing diabetic control (before probucol: hemoglobin A1, cholesterol, 10.7% +/- 2.7%; after probucol: 10.9% +/- 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Marine oil capsule therapy for the treatment of hyperlipidemia.

Because marine oil capsules may vary widely in their content of omega-3 fatty acids, saturated fat, and cholesterol composition and, therefore, their biologic potency, we compared the lipid-lowering effects of three representative preparations in patients with different forms of hyperlipidemia. The ester and triglyceride forms of marine oil both effectively lowered triglyceride, but the response of low-density lipoprotein cholesterol was variable; it declined modestly in patients with hypercholesterolemia and was either unchanged or increased in those with hypertriglyceridemia. The saturated fat and cholesterol content of the marine oil preparation appeared to influence the low-density lipoprotein cholesterol response. Therefore, marine oil capsules are useful for lowering levels of very-low-density lipoprotein cholesterol, but the large dose required to achieve and sustain this effect (4.5 g of omega-3 fatty acids, or nine to 18 capsules daily) may limit long-term compliance.

Docosahexaenoic Acids↗