Biomedical subjects

E J Murphy

Publications and source records attributed to E J Murphy.

At least 19 recordsLinked to original sources

PubMed2006

Dissociation between adipose tissue fluxes and lipogenic gene expression in ob/ob mice.

Recent evidence has been presented that expression of lipogenic genes is downregulated in adipose tissue of ob/ob mice as well as in human obesity, suggesting a functionally lipoatrophic state. Using (2)H(2)O labeling, we measured three adipose tissue biosynthetic processes concurrently: triglyceride (TG) synthesis, palmitate de novo lipogenesis (DNL), and cell proliferation (adipogenesis). To determine the effect of the ob/ob mutation (leptin deficiency) on these parameters, adipose dynamics were compared in ob/ob, leptin-treated ob/ob, food-restricted ob/ob, and lean control mice. Adipose tissue fluxes for TG synthesis, de novo lipogenesis (DNL), and adipogenesis were dramatically increased in ob/ob mice compared with lean controls. Low-dose leptin treatment (2 microg/day) via miniosmotic pump suppressed all fluxes to control levels or below. Food restriction in ob/ob mice only modestly reduced DNL, with no change in TG synthesis or adipogenesis. Measurement of mRNA levels in age-matched ob/ob mice showed generally normal expression levels for most of the selected lipid anabolic genes, and leptin treatment had, with few exceptions, only modest effects on their expression. We conclude that leptin deficiency per se results in marked elevations in flux through diverse lipid anabolic pathways in adipose tissue (DNL, TG synthesis, and cell proliferation), independent of food intake, but that gene expression fails to reflect these changes in flux.

Adipogenesis↗

PubMed2006

Modelling Southern Ocean ecosystems: krill, the food-web, and the impacts of harvesting.

The ecosystem approach to fisheries recognises the interdependence between harvested species and other ecosystem components. It aims to account for the propagation of the effects of harvesting through the food-web. The formulation and evaluation of ecosystem-based management strategies requires reliable models of ecosystem dynamics to predict these effects. The krill-based system in the Southern Ocean was the focus of some of the earliest models exploring such effects. It is also a suitable example for the development of models to support the ecosystem approach to fisheries because it has a relatively simple food-web structure and progress has been made in developing models of the key species and interactions, some of which has been motivated by the need to develop ecosystem-based management. Antarctic krill, Euphausia superba, is the main target species for the fishery and the main prey of many top predators. It is therefore critical to capture the processes affecting the dynamics and distribution of krill in ecosystem dynamics models. These processes include environmental influences on recruitment and the spatially variable influence of advection. Models must also capture the interactions between krill and its consumers, which are mediated by the spatial structure of the environment. Various models have explored predator-prey population dynamics with simplistic representations of these interactions, while others have focused on specific details of the interactions. There is now a pressing need to develop plausible and practical models of ecosystem dynamics that link processes occurring at these different scales. Many studies have highlighted uncertainties in our understanding of the system, which indicates future priorities in terms of both data collection and developing methods to evaluate the effects of these uncertainties on model predictions. We propose a modelling approach that focuses on harvested species and their monitored consumers and that evaluates model uncertainty by using alternative structures and functional forms in a Monte Carlo framework.

Animals↗

PubMed2006

Stable isotope methods for the in vivo measurement of lipogenesis and triglyceride metabolism.

Synthesis of fatty acids (via de novo lipogenesis) and triglycerides are important factors in fat accumulation and the efficiency of animal production. Recently, new stable isotope methods using heavy water (2H2O) have made possible the safe, and relatively easy, measurement of both of these processes in vivo in animals and humans over prolonged periods. These methods also provide information on the relative contribution of glycolysis and glyceroneogenesis to triglyceride synthesis under different physiological settings. The data suggest that numerous dietary factors, including nutrient composition and caloric content, may affect de novo lipogenesis. Significant differences in de novo lipogenesis have also been seen across species and in different tissues. The rates of triglyceride synthesis have been shown to be affected by diet and to differ significantly between different adipose depots, with metabolically active depots (e.g., visceral fat) having much more rapid triglyceride turnover than subcutaneous depots. Dietary fat and the peroxisome proliferator-activated-gamma agonist rosiglitazone have both been shown to influence triglyceride synthesis rates and to increase glyceroneogenesis. A significant portion of triglyceride synthesis is not related to triglyceride accumulation but rather is secondary to active lipolysis and reesterification. The application of these new techniques to animals other than rodents will undoubtedly enhance our understanding of adipose tissue biology and could lead to new methods for improving animal production.

Animals↗

PubMed2006

Effect of processing flax in beef feedlot diets on performance, carcass characteristics, and trained sensory panel ratings.

To assess the effects of flax addition and flax processing on feedlot performance and carcass characteristics, 128 yearling beef heifers (360 +/- 14 kg of initial BW) were blocked by weight and assigned randomly to feedlot diets that included no flax (control), whole flax (WHL), rolled flax (RLD; 1,300 microm), or ground flax (GRD; 700 microm). Heifers were fed a growth diet (31% corn, 30% corn silage, 18% barley malt pellets, 14% alfalfa, 4% linseed meal, and 3% supplement; DM basis) for 56 d, after which they were adapted to a finishing diet (79% corn, 7% corn silage, 7% alfalfa, 4.75% linseed meal, and 2.25% supplement; DM basis). In WHL, RLD, and GRD, flax replaced all linseed meal and partially replaced corn at 8% of diet DM. All diets provided 0.5 mg of melengestrol acetate, 2,000 IU of vitamin E, and 232 mg of monensin per heifer daily. Cattle were slaughtered by block after 96, 97, and 124 (2 blocks) d on feed. At 24 h postmortem, carcass data were collected, and a portion of the loin was removed, vacuum-packaged, and aged for 14 d. After aging, 2 steaks were removed from each loin for Warner-Bratzler shear force measurement, sensory panel evaluation, and fatty acid analysis (approximately 100 g of muscle was collected). Flax inclusion (WHL, RLD, and GRD vs. control) did not affect DMI (P = 0.79), fat thickness over the 12th rib (P = 0.32), or LM area (P = 0.23). Flax inclusion increased ADG (P = 0.006), G:F (P = 0.006), and USDA yield grade (P = 0.01). Flax processing (RLD and GRD vs. WHL) increased ADG (P = 0.05), G:F (P = 0.08), and apparent dietary NEm and NEg (P = 0.003). Muscle from heifers fed flax had greater phospholipid 18:3n-3 (P < 0.001), 20:5n-3 (P < 0.001), 22:5n-3 (P < 0.001), and 22:6n-3 (P = 0.02) fractions, and greater neutral lipid 18:3n-3 (P < 0.001). Feeding 8% flax to feedlot heifers increased gain and efficiency, and processing flax increased available energy and resulted in increased efficiency of gain. Feeding 8% flax also increased levels of n-3 fatty acids in fresh beef.

Animal Feed↗

PubMed2005

Fatty acid incorporation is decreased in astrocytes cultured from alpha-synuclein gene-ablated mice.

Because alpha-synuclein may function as a fatty acid binding protein, we measured fatty acid incorporation into astrocytes isolated from wild-type and alpha-synuclein gene-ablated mice. alpha-Synuclein deficiency decreased palmitic acid (16:0) incorporation 31% and arachidonic acid [20:4 (n-6)] incorporation 39%, whereas 22:6 (n-3) incorporation was unaffected. In neutral lipids, fatty acid targeting of 20:4 (n-6) and 22:6 (n-3) (docosahexaenoic acid) to the neutral lipid fraction was increased 1.7-fold and 1.6-fold, respectively, with an increase in each of the major neutral lipids. This was consistent with a 3.4- to 3.8-fold increase in cholesteryl ester and triacylglycerol mass. In the phospholipid fraction, alpha-synuclein deficiency decreased 16:0 esterification 39% and 20:4 (n-6) esterification 43% and decreased the distribution of these fatty acids, including 22:6 (n-3), into this lipid pool. alpha-Synuclein gene-ablation significantly decreased the trafficking of these fatty acids to phosphatidylinositol. This observation is consistent with changes in phospholipid fatty acid composition in the alpha-synuclein-deficient astrocytes, including decreased 22:6 (n-3) content in the four major phospholipid classes. In summary, these studies demonstrate that alpha-synuclein deficiency significantly disrupted astrocyte fatty acid uptake and trafficking, with a marked increase in fatty acid trafficking to cholesteryl esters and triacylglycerols and decreased trafficking to phospholipids, including phosphatidylinositol.

Animals↗

PubMed2005

Acute pain management pharmacology for the patient with concurrent renal or hepatic disease.

The clinical utility of most analgesic drugs is altered in the presence of patients with impaired renal or hepatic function not simply because of altered clearance of the parent drug, but also through production and accumulation of toxic or therapeutically active metabolites. Some analgesic agents may also aggravate pre-existing renal and hepatic disease. A search was performed, taking in published articles and pharmaceutical data to determine available evidence for managing acute pain effectively and safely in these two patient groups. The resulting information consisted mainly of small group pharmacokinetic studies or case reports, which included a large variation in degree of organ dysfunction. In the presence of renal impairment, those drugs which exhibit the safest pharmacological profile are alfentanil, buprenorphine, fentanyl, ketamine, paracetamol (except with compound analgesics), remifentanil and sufentanil. none of these deliver a high active metabolite load, or suffer from significantly prolonged clearance. Amitriptyline, bupivacaine, clonidine, gabapentin, hydromorphone, levobupivacaine, lignocaine, methadone, mexiletine, morphine, oxycodone and tramadol have been used in the presence of renal failure, but do require specific precautions, usually dose reduction. Aspirin, dextropropoxyphene, non-steroidal anti-inflammatory drugs and pethidine, should not be used in the presence of chronic renal failure due to the risk of significant toxicity. In the presence of hepatic impairment, most drugs are subject to significantly impaired clearance and increased oral bioavailability, but are poorly studied in the clinical setting. The agent least subject to alteration in this context is remifentanil; however the drugs' potency has other inherent dangers. Other agents must only be used with caution and close patient monitoring. Amitriptyline, carbamazepine and valproate should be avoided as the risk of fulminant hepatic failure is higher in this population, and methadone is contraindicated in the presence of severe liver disease.

Analgesics↗

PubMed2003

Measurement of TG synthesis and turnover in vivo by 2H2O incorporation into the glycerol moiety and application of MIDA.

A method is presented for measurement of triglyceride (TG) synthesis that can be applied to slow-turnover lipids. The glycerol moiety of TG is labeled from 2H2O, and mass isotopomer distribution analysis (MIDA) is applied. Mice and rats were given 4-8% 2H2O in drinking water; TG-glycerol was isolated from adipose and liver during < or =12-wk of 2H2O labeling. Mass isotopomer abundances in the glycerol moiety of TG were measured by GC-MS. The combinatorial pattern of isotopomers revealed the number of H atoms in glycerol incorporating label from 2H2O (n) to be 3.8-4.0 of a possible 5 for adipose tissue and 4.6-4.8 for liver TG. Hepatic TG-glycerol in fact reached 97% predicted maximal value of label incorporation (4.4-4.6 x body 2H2O enrichment), indicating near-complete replacement of the liver TG pool. Label incorporation into adipose tissue revealed turnover of mesenteric TG to be faster (k = 0.21 day-1) than other depots (k = 0.04-0.06 day-1) in mice. TG isolated from subcutaneous depots of growing adult rats plateaued at 85-90% of calculated maximal values at 12 wk (k = 0.05 day-1), excluding significant dilution by unlabeled alpha-glycerol phosphate. Turnover of plasma TG, modeled from 2H incorporation over 60 min, was 0.06 min-1 (half-life 11.5 min). In summary, use of 2H2O labeling with MIDA of TG-glycerol allows measurement of new alpha-glycerol phosphate-derived TG synthesis and turnover. The hypothesis that mesenteric TG is more lipolytically active than other depots, previously difficult to prove by isotope dilution techniques, was confirmed by this label incorporation approach.

Adipose Tissue↗

PubMed2002

Environmental change and Antarctic seabird populations.

Recent changes in Antarctic seabird populations may reflect direct and indirect responses to regional climate change. The best long-term data for high-latitude Antarctic seabirds (Adélie and Emperor penguins and snow petrels) indicate that winter sea-ice has a profound influence. However, some effects are inconsistent between species and areas, some in opposite directions at different stages of breeding and life cycles, and others remain paradoxical. The combination of recent harvest driven changes and those caused by global warming may produce rapid shifts rather than gradual changes.

Animals↗

PubMed2002

Intra-arterial injection of metoclopramide, midazolam, propofol and pethidine.

A case is reported in which metoclopramide, midazolam, propofol, and pethidine were injected arterially during the course of anaesthesia, resulting in oedema and discolouration of the hand initially, but no long-term sequelae. An AVI 470 pump (3M Corporation) was used to control the infusion, andprevented backflow through a cannula which was unintentionally sited in an artery rather than a vein. Few anaesthetic drugs have their effects well documented when given arterially, and in particular, there were no previous reported cases involving metoclopramide in this context. The pharmacology of metoclopramide is discussed with reference to the drug's known effects on vascular beds and platelet function.

Abdominal Wall↗

PubMed2001

High-dose methylprednisolone treatment in experimental focal cerebral ischemia.

Previous studies using steroids for experimental focal stroke have demonstrated conflicting results, possibly related to dose used or ischemic models employed. In this study we examined high-dose methylprednisolone treatment following permanent and temporary focal cerebral ischemia in the rat. Focal stroke was induced in spontaneously hypertensive rats by permanent right common carotid and either permanent or 3 h of temporary middle cerebral artery (MCA) occlusion. Methylprednisolone (105 mg/kg) was administered intra-arterially. Infarct volume was measured at 24 h after permanent and temporary MCA occlusion. Cerebral edema was determined by measuring right and left hemispheric volumes and water content 24 h after permanent MCA occlusion in one experiment. Methylprednisolone, whether administered in divided doses over 12 h (n = 15 in each group) or a single bolus (n = 9 per group), had no effect on infarct volume after permanent MCA occlusion. Methylprednisolone treatment also had no influence on cerebral edema (n = 9 per group). In two different experiments, methylprednisolone given in divided doses over 12 h (n = 11, n = 25) after temporary MCA occlusion decreased infarct volume (P < 0.05) by 20% compared with saline controls (n = 10, n = 25). High dose methylprednisolone decreased infarct volume following temporary, but not permanent, focal ischemia. The benefit suggests that high dose methylprednisolone may prove useful clinically if reperfusion can be established with thrombolytic agents. Furthermore, the differential treatment effect in the setting of comparable ischemic insults implies that different modifiable biochemical processes may be present during temporary but not permanent focal ischemia, thus providing indirect evidence for reperfusion injury.

Animals↗

PubMed2000

A continuous fluorometric assay for phospholipase A(2) activity in brain cytosol.

Alterations in phospholipase A(2) (PLA(2)) activity have been implicated in Alzheimer disease and other neurological disorders, although brain PLA(2) activity is currently measured using lengthy, non-continuous assays. We describe herein a rapid, continuous assay in which we measured PLA(2) activity in mouse brain cytosol (CB-57). Brains were homogenized in HEPES buffer (pH 7.5) and the cytosolic fraction was prepared by centrifugation at 25000xg for 20 min, followed by centrifugation of the supernatant at 100000xg for 60 min. Cytosolic protein content was determined using the Bradford assay. Pyrene labeled phosphatidylcholine was added to 50 microg of cytosolic protein in Tris buffer (pH 8.0) containing fatty acid free-bovine serum albumin for a final assay volume of 2 ml. Assay temperature was maintained at 30+/-1 degrees C. The excitation wavelength was 345 nm and emission was measured at 377 nm. Fluorescence intensity was converted to molar concentrations using a standard curve. Under these conditions, bromoenol lactone inhibited up to 58% of the PLA(2) activity with an IC(50) of 0.5 microM. In a separate experiment, lack of appreciable alternative acylhydrolase activity was verified chromatographically. Using this method, brain PLA(2) activity can be measured in a continuous, rapid, and sensitive manner.

Animals↗

PubMed2000

Phospholipase A2 activity is decreased selectively in the hippocampus of aged apolipoprotein E deficient mice.

Because apolipoprotein E (ApoE) deficient mice have cognitive deficits (Neurosci. Lett., 199 (1995) 1-4; Neuroscience, 92 (1999) 1273-1286; Brain Res., 752 (1997) 189-196) that may involve decreased phospholipase A(2) (PLA(2)) activity (Neuroscience, 92 (1999) 1273-1286), striatal, hippocampal, and parieto-temporal PLA(2) activity was measured in cytosol from 3 and 20-month-old ApoE deficient and control mice. Samples were homogenized and cytosol prepared by ultracentrifugation. PLA(2) activity in each cytosolic fraction was measured in triplicate using a continuous fluorometric assay (J. Neurosci. Methods (2000) in press). In 3-month-old animals, there was a trend for decreased hippocampal PLA(2) activity between groups. In 20-month-old animals, hippocampal PLA(2) activity was significantly (P=0.0304) decreased nearly 20% in ApoE deficient mice as compared to age-matched control mice. No differences were found in other brain regions, although activity in the striatal samples were nearly 65% less than in the other two regions.

Aging↗

PubMed2000

Phospholipid composition and levels are altered in Down syndrome brain.

Phospholipid composition (mol %) and levels (nmol/mg protein) were determined in postmortem frontal cortical and cerebellar gray matter from older Down Syndrome (DS) patients (age range 38-68 years) and from control subjects. Neither DS nor control tissue exhibited any age-dependent alteration in phospholipid composition or levels. Total phospholipid content was significantly reduced approximately 20% in DS frontal cortex and cerebellum relative to these regions in control tissue. Individual phospholipid levels were also reduced in DS frontal cortex and cerebellum, including a specific 37% decrease in phosphatidylinositol (PtdIns) and a nearly 35% decrease in ethanolamine plasmalogen. Because of the large decrease in phospholipid content in DS brain, the cholesterol/phospholipid ratio was calculated for each group. There was no significant difference in this ratio between groups, indicative of compensatory changes to keep the cholesterol/phospholipid ratio constant. Despite the large changes in DS brain phospholipid levels, significant changes in composition were limited to a 18% decrease in PtdIns mol % and a 22% increase in the mol % of sphingomyelin. These results suggest either a decrease in membrane phospholipids due to a loss of dendrites and dendritic spines, or a general defect in brain lipid metabolism in older DS subjects. The proportionally greater alterations in PtdIns and PlsEtn levels, indicate that the metabolism of these two phospholipids was affected to a greater extent than the other phospholipids. Further, because these changes are found in both the frontal cortical and cerebellar gray matter, they likely are related to the Down syndrome condition rather than to Alzheimer neuropathology.

Adult↗

PubMed2000

Liver and intestinal fatty acid-binding protein expression increases phospholipid content and alters phospholipid fatty acid composition in L-cell fibroblasts.

Although fatty acid-binding proteins (FABP) differentially affect fatty acid uptake, nothing is known regarding their role(s) in determining cellular phospholipid levels and phospholipid fatty acid composition. The effects of liver (L)- and intestinal (I)-FABP expression on these parameters were determined using stably transfected L-cells. Expression of L- and I-FABP increased cellular total phospholipid mass (nmol/mg protein) 1.7- and 1.3-fold relative to controls, respectively. L-FABP expression increased the masses of choline glycerophospholipids (ChoGpl) 1.5-fold, phosphatidylserine (PtdSer) 5.6-fold, ethanolamine glycerophospholipids 1.4-fold, sphingomyelin 1.7-fold, and phosphatidylinositol 2.6-fold. In contrast, I-FABP expression only increased the masses of ChoGpl and PtdSer, 1.2- and 3.1-fold, respectively. Surprisingly, both L- and I-FABP expression increased ethanolamine plasmalogen mass 1.6- and 1.1-fold, respectively, while choline plasmalogen mass was increased 2.3- and 1.7-fold, respectively. The increase in phospholipid levels resulted in dramatic 48 and 33% decreases in the cholesterol-to-phospholipid ratio in L- and I-FABP expressing cells, respectively. L-FABP expression generally increased polyunsaturated fatty acids, primarily by increasing 20:4n-6 and 22:6n-3, while decreasing 18:1n-9 and 16:1n-7. I-FABP expression generally increased only 20:4n-6 proportions. Hence, expression of both I- and L-FABP differentially affected phospholipid mass, class composition, and acyl chain composition. Although both proteins enhanced phospholipid synthesis, the effect of L-FABP was much greater, consistent with previous work suggesting that these two FABP differentially affect lipid metabolism.

Animals↗

PubMed2000

Intravenously injected [1-14C]arachidonic acid targets phospholipids, and [1-14C]palmitic acid targets neutral lipids in hearts of awake rats.

The differential uptake and targeting of intravenously infused [1-14C]palmitic ([1-14C]16:0) and [1-14C]arachidonic ([1-14C]20:4n-6) acids into heart lipid pools were determined in awake adult male rats. The fatty acid tracers were infused (170 microCi/kg) through the femoral vein at a constant rate of 0.4 mL/min over 5 min. At 10 min postinfusion, the rats were killed using pentobarbital. The hearts were rapidly removed, washed free of exogenous blood, and frozen in dry ice. Arterial blood was withdrawn over the course of the experiment to determine plasma radiotracer levels. Lipids were extracted from heart tissue using a two-phase system, and total radioactivity was measured in the nonvolatile aqueous and organic fractions. Both fatty acid tracers had similar plasma curves, but were differentially distributed into heart lipid compartments. The extent of [1-14C]20:4n-6 esterification into heart phospholipids, primarily choline glycerophospholipids, was elevated 3.5-fold compared to [1-14C]16:0. The unilateral incorporation coefficient, k*, which represents tissue radioactivity divided by the integrated plasma radioactivity for heart phospholipid, was sevenfold greater for [1-14C]20:4n-6 than for [1-14C]16:0. In contrast, [1-14C]16:0 was esterified mainly into heart neutral lipids, primarily triacylglycerols (TG), and was also found in the nonvolatile aqueous compartment. Thus, in rat heart, [1-14C]20:4n-6 was primarily targeted for esterification into phospholipids, while [1-14C]16:0 was targeted for esterification into TG or metabolized into nonvolatile aqueous components.

Animals↗

PubMed2000

Phospholipid composition and levels are not altered in fibroblasts bearing presenilin-1 mutations.

Lipid alterations have been reported in brain regions affected by Alzheimer disease (AD). The mechanisms causing these changes are poorly understood because it is difficult to study dynamic, biochemical processes in post-mortem brain. Fibroblasts derived from AD patients offer an alternative model to study disease-related alterations in lipid metabolism. Therefore, we measured the phospholipid levels and composition of fibroblasts from individuals bearing two different presenilin-1 mutations and compared these values to appropriate control fibroblasts. There were no differences between groups in phospholipid composition or in individual phospholipid levels, including the plasmalogens. Cholesterol levels and the cholesterol/phospholipid ratio were not different between presenilin-1 mutation bearing and control fibroblasts. Although these presenilin-1 mutation bearing fibroblasts have a number of biochemical changes related to AD, the absence of a change in phospholipid levels suggests that under these conditions, these cells are not useful in studying the mechanisms underlying the alterations in brain phospholipid levels associated with AD. However, these results do not preclude the possible use of other fibroblasts bearing AD-related mutations, e.g., APP mutations, to examine AD-related changes in brain lipid metabolism, or of these fibroblasts under different conditions.

Alzheimer Disease↗

PubMed2000

Troglitazone-induced fulminant hepatic failure. Acute Liver Failure Study Group.

The three reported cases demonstrate that troglitazone is an idiosyncratic hepatotoxin that can lead to irreversible liver injury. Thus, troglitazone should be prescribed with caution and should not be used as a first-line agent in the treatment of type II DM when potentially less toxic alternatives are available. It remains to be seen whether the hepatotoxicity associated with troglitazone is a drug-class effect or specific to troglitazone. Other thiazolidinediones currently in clinical trials may be able to provide the therapeutic benefits of troglitazone without significant hepatotoxicity. If troglitazone is used, frequent monitoring of serum aminotransferases and symptoms is mandatory. However, as illustrated by these and other cases reported to date, the onset of troglitazone-induced liver injury is insidious and temporally variable. Thus, the value of close monitoring and when, if ever, it is safe to stop such monitoring are currently unclear.

Chromans↗

PubMed2000

Sterol carrier protein-2 localization in endoplasmic reticulum and role in phospholipid formation.

Although sterol carrier protein-2 (SCP-2; also called nonspecific lipid transfer protein) binds fatty acids and fatty acyl-CoAs, its role in fatty acid metabolism is not fully understood. L-cell fibroblasts stably expressing SCP-2 were used to resolve the relationship between SCP-2 intracellular location and fatty acid transacylation in the endoplasmic reticulum. Indirect immunofluorescence double labeling and laser scanning confocal microscopy detected SCP-2 in peroxisomes > endoplasmic reticulum > mitochondria > lysosomes. SCP-2 enhanced incorporation of exogenous [(3)H]oleic acid into phospholipids and triacylglycerols of overexpressing cells 1.6- and 2.5-fold, respectively, stimulated microsomal incorporation of [1-(14)C]oleoyl-CoA into phosphatidic acid in vitro 13-fold, and exhibited higher specificity for unsaturated versus saturated fatty acyl-CoA. SCP-2 enhanced the rate-limiting step in microsomal phosphatidic acid biosynthesis mediated by glycerol-3-phosphate acyltransferase. SCP-2 also enhanced microsomal acyl-chain remodeling of phosphatidylethanolamine up to fivefold and phosphatidylserine twofold, depending on the specific fatty acyl-CoA, but had no effect on other phospholipid classes. In summary, these results were consistent with a role for SCP-2 in phospholipid synthesis in the endoplasmic reticulum.

Acyl Coenzyme A↗