Role In Fatty Acid Metabolism Research Articles

Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal

Acetyl-CoA carboxylases (ACC1 and ACC2) catalyze the carboxylation of acetyl-CoA to form malonyl-CoA, an intermediate metabolite that plays a pivotal role in the regulation of fatty acid metabolism. We previously reported that ACC2 null mice are viable, and that ACC2 plays an important role in the regulation of fatty acid oxidation through the inhibition of carnitine palmitoyltransferase I, a mitochondrial component of the fatty-acyl shuttle system. Herein, we used gene targeting to knock out the ACC1 gene. The heterozygous mutant mice (Acc1(+/-)) had normal fertility and lifespans and maintained a similar body weight to that of their wild-type cohorts. The mRNA level of ACC1 in the tissues of Acc1(+/-) mice was half that of the wild type; however, the protein level of ACC1 and the total malonyl-CoA level were similar. In addition, there was no difference in the acetate incorporation into fatty acids nor in the fatty acid oxidation between the hepatocytes of Acc1(+/-) mice and those of the wild type. In contrast to Acc2(-/-) mice, Acc1(-/-) mice were not detected after mating. Timed pregnancies of heterozygotes revealed that Acc(-/-) embryos are already undeveloped at embryonic day (E)7.5, they die by E8.5, and are completely resorbed at E11.5. Our previous results of the ACC2 knockout mice and current studies of ACC1 knockout mice further confirm our hypotheses that malonyl-CoA exists in two independent pools, and that ACC1 and ACC2 have distinct roles in fatty acid metabolism.

Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery

Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism in most living organisms. Mice deficient in ACC2 have continuous fatty acid oxidation and reduced body fat and body weight, validating this enzyme as a target for drug development against obesity, diabetes and other symptoms of the metabolic syndrome. ACC is a biotin-dependent enzyme and catalyzes the carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is a multi-subunit enzyme in most prokaryotes, whereas it is a large, multi-domain enzyme in most eukaryotes. The activity of the enzyme can be controlled at the transcriptional level as well as by small molecule modulators and covalent modification. This review will summarize the structural information that is now available for both the BC and CT enzymes, as well as the molecular mechanism of action of potent ACC inhibitors. The current intense research on these enzymes could lead to the development of novel therapies against metabolic syndrome and other diseases.

Fatty acid metabolism as a target for obesity treatment

Although metabolites and energy balance have long been known to play roles in the regulation of food intake, the potential role of fatty acid metabolism in this process has been considered only recently. Fatty acid synthase (FAS) catalyzes the condensation of acetyl-CoA and malonyl-CoA to generate long-chain fatty acids in the cytoplasm, while the breakdown of fatty acids (β-oxidation) occurs in mitochondria and is regulated by carnitine palmitoyltransferase-1 (CPT-1), the rate-limiting step for the entry of fatty acids into the mitochondria. Inhibition of FAS using cerulenin or synthetic FAS inhibitors such as C75 reduces food intake and induces profound reversible weight loss. Subsequent studies reveal that C75 also stimulates CPT-1 and increases β-oxidation. Hypotheses as to the mechanisms by which C75 and cerulenin mediate their effects have been proposed. Centrally, these compounds alter the expression profiles of feeding-related neuropeptides, often inhibiting the expression of orexigenic peptides. Whether through centrally mediated or peripheral mechanisms, C75 also increases energy consumption, which contributes to weight loss. In vitro and in vivo studies demonstrate that at least part of C75's effects is mediated by modulation of AMP-activated protein kinase (AMPK), a known peripheral energy-sensing kinase. Collectively, these data suggest a role for fatty acid metabolism in the perception and regulation of energy balance.

Fatty acid transport proteins and insulin resistance

Disturbed fatty acid metabolism and homeostasis is associated with insulin resistance. The aim of this review, therefore, is to summarize recent developments relating to the relevance and importance of the fatty acid transport proteins (FATPs) in the aetiology of insulin resistance. In particular, the potential differences between the six members of the FATP family will be considered. FATP1 knockout mice failed to develop insulin resistance associated with lipid infusion or a high-fat diet, as wild-type mice did. FATP1-mediated fatty acid uptake may cause intramuscular lipid accumulation leading to insulin resistance in muscle if the fatty acids are not oxidized. While mouse models demonstrated an absolute requirement for FATP4 for survival, they provided no direct evidence for a role of FATP4 in insulin resistance. However, expression of FATP4 in human adipose tissue was increased in obesity (independent of genetic factors). While other members of the FATP family have important roles in fatty acid metabolism, they have not been clearly linked to insulin resistance. FATP-mediated fatty acid uptake may be driven by intrinsic acyl-CoA synthase activity. Any role in the development of insulin resistance is likely to be different for each member of the FATP family. So far, both FATP1 and FATP4 have been associated with parameters related to insulin resistance. Whether increased FATP-mediated fatty acid uptake is beneficial or detrimental may be dependent on the tissue in question and on the subsequent fate of the fatty acids. These issues remain to be resolved.

A Mechanism for the Potent Inhibition of Eukaryotic Acetyl-Coenzyme A Carboxylase by Soraphen A, a Macrocyclic Polyketide Natural Product

Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism. Soraphen A, a macrocyclic polyketide natural product, is a nanomolar inhibitor against the biotin carboxylase (BC) domain of human, yeast, and other eukaryotic ACCs. Here we report the crystal structures of the yeast BC domain, alone and in complex with soraphen A. Soraphen has extensive interactions with an allosteric site, about 25 Å from the active site. The specificity of soraphen is explained by large structural differences between the eukaryotic and prokaryotic BC in its binding site, confirmed by our studies on the effects of single-site mutations in this binding site. Unexpectedly, our structures suggest that soraphen may bind in the BC dimer interface and inhibit the BC activity by disrupting the oligomerization of this domain. Observations from native gel electrophoresis confirm this structural insight. The structural information provides a foundation for structure-based design of new inhibitors against these enzymes.

Roles of peroxisome proliferator-activated receptor delta (PPARδ) in the control of fatty acid catabolism. A new target for the treatment of metabolic syndrome

Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors playing important regulatory functions in development and metabolism. PPARα and PPARγ are the most extensively examined and characterized, mainly because they are activated by marketed hypolipidemic and insulin sensitizer compounds, such as fibrates and thiazolidinediones. It has been established that the third member of the family, PPARδ is implicated in developmental regulations, but until recently, its role in metabolism remained unclear. The availability of specific PPARδ agonists and of appropriate cellular and animal models revealed that PPARδ plays a crucial role in fatty acid metabolism in several tissues. Treatment of obese animals with PPARδ agonists results in normalization of metabolic parameters and reduction of adiposity. Activation of the nuclear receptor promotes fatty acid burning in skeletal muscle and adipose tissue by upregulation of fatty acid uptake, β-oxidation and energy uncoupling. PPARδ is also involved in the adaptive metabolic responses of skeletal muscle to environmental changes, such as long-term fasting or physical exercise, by controlling the number of oxidative myofibers. These observations strongly suggest that PPARδ agonists may have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption and decreasing obesity.

Carnitine system in uremic patients: Molecular and clinical aspects

Carnitine is a small water-soluble molecule that is present in almost all animal species. It plays an indispensable role in fatty acid metabolism, where it is involved in the transport of activated fatty acids between different cellular compartments. Uremic patients, as well as patients with chronic renal failure, appear to have abnormal renal handling of carnitine leading to dyslipidemia, lethargy, muscular weakness, hypotension, cardiac dysfunction and arrhythmias, and recurrent cramps. It often is difficult to distinguish these symptoms from similar ones related to uremia and dialysis. Many investigators have advocated L-carnitine supplementation in an attempt to alleviate carnitine deficiencies, and good results from this therapy have been reported. Moreover, several studies have shown that L-carnitine supplementation improves the response to erythropoietin. Chronic inflammation is another particular aspect affecting these patients. Anti-inflammatory properties of L-carnitine in hemodialysis patients have been shown by our group. Treatment with L-carnitine (20 mg/kg, given intravenously at the end of each dialysis session for 6 mo), significantly decreased serum C-reactive protein (CRP) levels, a proinflammatory cytokine known to inhibit erythropoiesis. Moreover, data from published literature are indicative of L-carnitine modulation of the immune system by the activation of glucocorticoid receptors and the modulation of the transcription of glucocorticoid-responsive genes. Our study showed that in these patients, treatment with L-carnitine has been able to improve their body mass index, likely by promoting a positive protein balance. This aspect is strictly correlated with the status of insulin resistance, which is well described in patients with renal diseases. Many studies showed that carnitine allowed mitochondrial fatty acid usage to link to the rate of glucose usage, thus improving insulin resistance. In conclusion, clinical beneficial effects of L-carnitine treatment on patients suffering from renal diseases are supported by molecular evidence involving both inflammatory and metabolic aspects of the disease.

Stress‐ (and Diet‐) Related Regulation of Hepatic Nuclear Receptors and Its Relevance for ABC‐Transporter Functions

Nuclear receptors (NRs) play an important role in maintaining cellular homeostasis. With clearly established roles in fatty acid metabolism and inflammation, peroxisome proliferator activated receptors (PPARs) and other nuclear receptors are essential in liver functioning. However, much less is known about the regulation of NRs themselves during inflammatory processes in the liver. Interestingly PPARs and other NRs are negative acute phase proteins because they become rapidly downregulated during the acute phase response. However, PPARs have important roles in modulating inflammatory responses. One of the mechanisms by which dietary or inflammatory stress is relieved involves the hepatic adenosine triphosphate‐binding cassette (ABC) transporter proteins, which import and export a wide variety of substrates. These ABC transporters are under close control of several NRs. Because NRs play important roles in fatty acid metabolism and inflammation as well as in the regulation of bile production, they are reviewed here with respect to their role in dietary and stress‐related responses of the liver and their impact on the regulation and function of hepatic ABC transporters.

Changes in the Fatty Acid Composition of Hepatopancreas of the Mollusk Mytilus trossulus Fed on Microalgae

The influence of diet on the fatty acid composition of the hepatopancreas of Mytilus trossulus was studied. Three groups of mollusks were fed monocultures of the microalgae Phaeodactylum tricornutum, Chaetoceros muelleri (Bacillariophyceae), and Nannochloropsis sp. (Eustigmatophyceae) for 10 days. After 10 days, the proportion of polyunsaturated fatty acids, mainly eicosapentaenoic and docosahexaenoic, increased in the total lipids of the hepatopancreas in all mollusk groups. The content of saturated fatty acids in the mussel tissues decreased and was not dependent on the amount in the algal diet. Toward the end of the experiment, the fatty acid composition of the hepatopancreas of mussels was similar irrespective of the fatty acid composition of their food. The fatty acid analysis of M. trossulus feces suggests a selective assimilation by mussels of predominantly the n-3 polyunsaturated fatty acids. The role of fatty acid metabolism in M. trossulus is discussed.

The Acyl-CoA Synthetase “Bubblegum” (Lipidosin): FURTHER CHARACTERIZATION AND ROLE IN NEURONAL FATTY ACID β-OXIDATION

Acyl-CoA synthetases play a pivotal role in fatty acid metabolism, providing activated substrates for fatty acid catabolic and anabolic pathways. Acyl-CoA synthetases comprise numerous proteins with diverse substrate specificities, tissue expression patterns, and subcellular localizations, suggesting that each enzyme directs fatty acids toward a specific metabolic fate. We reported that hBG1, the human homolog of the acyl-CoA synthetase mutated in the Drosophila mutant "bubblegum," belongs to a previously unidentified enzyme family and is capable of activating both long- and very long-chain fatty acid substrates. We now report that when overexpressed, hBG1 can activate diverse saturated, monosaturated, and polyunsaturated fatty acids. Using in situ hybridization and immunohistochemistry, we detected expression of mBG1, the mouse homolog of hBG1, in cerebral cortical and cerebellar neurons and in steroidogenic cells of the adrenal gland, testis, and ovary. The expression pattern and ability of BG1 to activate very long-chain fatty acids implicates this enzyme in the pathogenesis of X-linked adrenoleukodystrophy. In neuron-derived Neuro2a cells, mBG1 co-sedimented with mitochondria and was found in small vesicular structures located in close proximity to mitochondria. RNA interference was used to decrease mBG1 expression in Neuro2a cells and led to a 30-35% decrease in activation and beta-oxidation of the long-chain fatty acid, palmitate. These results suggest that in Neuro2a cells, mBG1-activated long-chain fatty acids are directed toward mitochondrial degradation. mBG1 appears to play a minor role in very long-chain fatty acid activation in these cells, indicating that other acyl-CoA synthetases are necessary for very long-chain fatty acid metabolism in Neuro2a cells.

Book review

Acyl-CoA Δ9-desaturases play essential roles in fatty acid metabolism and the regulation of cell membrane fluidity. In this research, a cDNA sequence was obtained from Trichoplusia ni adult fat body mRNA by using RT–PCR with degenerate primers based on other characterized Δ9-desaturase sequences. The remainder of the sequence was amplified using 3′- and 5′-RACE. A 1439 bp cDNA reconstructed from three overlapping PCR products contains an ORF encoding a 353-amino acids (aa) protein that shows clear homology (greater than 50% aa identity and greater than 65% aa similarity to characterized insect and vertebrate desaturases). The ORF of this cDNA was subcloned into an expression vector, which relieved the unsaturated fatty acid (UFA) auxotrophy of a desaturase-deficient yeast strain following genetic transformation. The newly characterized desaturase from T. ni produced fatty acids Δ9-16 and Δ9-18 in a 1:6 ratio, compared to a 5:1 ratio, respectively, with the yeast Δ9 desaturase. A Northern blot hybridization and a RT–PCR experiment showed that temporal and tissue-specific patterns of expression of the corresponding mRNA are distinct from those of the Δ11-desaturase mRNA present in the pheromone glands of adult females. Based on its homology to other desaturases, the widespread distribution of its corresponding mRNA in various tissues, and its functional assay, we conclude that this cDNA encodes the apoprotein corresponding to the desaturase component of the metabolic Δ9-desaturase complex of T. ni.

Lipids and insulin resistance: what we've learned at the Fourth International Smolenice Symposium.

A summary of the Fourth International Smolenice Symposium on Lipids and Insulin Resistance focusing on "The Role of Fatty Acid Metabolism and Fuel Partitioning" is provided. Highlights and issues of the conference are mentioned, as well as strategies for the future.

Preface

Annals of the New York Academy of SciencesVolume 967, Issue 1 p. xiii-xv Preface IWAR KLIMEŠ, Corresponding Author IWAR KLIMEŠ Diabetes and Nutrition Research Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, SK-83306 Bratislava, Slovak RepublicAddress for correspondence: Iwar Klimeš, Diabetes and Nutrition Research Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlárska 3, SK-83306 Bratislava, Slovak Republic. Voice/fax: 421-7-5466-2687; ueeniwar@savba.savba.sk.Search for more papers by this authorELENA ŠEBÖKOVÁ, ELENA ŠEBÖKOVÁ Diabetes and Nutrition Research Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, SK-83306 Bratislava, Slovak RepublicSearch for more papers by this author IWAR KLIMEŠ, Corresponding Author IWAR KLIMEŠ Diabetes and Nutrition Research Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, SK-83306 Bratislava, Slovak RepublicAddress for correspondence: Iwar Klimeš, Diabetes and Nutrition Research Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlárska 3, SK-83306 Bratislava, Slovak Republic. Voice/fax: 421-7-5466-2687; ueeniwar@savba.savba.sk.Search for more papers by this authorELENA ŠEBÖKOVÁ, ELENA ŠEBÖKOVÁ Diabetes and Nutrition Research Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, SK-83306 Bratislava, Slovak RepublicSearch for more papers by this author First published: 24 January 2006 https://doi.org/10.1111/j.1749-6632.2002.tb04256.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume967, Issue1LIPIDS AND INSULIN RESISTANCE: THE ROLE OF FATTY ACID METABOLISM AND FUEL PARTITIONINGJune 2002Pages xiii-xv RelatedInformation

Induction of human liver X receptor alpha gene expression via an autoregulatory loop mechanism.

The liver X receptors (LXRs), members of the nuclear receptor superfamily, play an important role in controlling lipid homeostasis by activating several genes involved in reverse cholesterol transport. These include members of the ATP binding cassette (ABC) superfamily of transporter proteins ABCA1 and ABCG1, surface constituents of plasma lipoproteins like apolipoprotein E, and cholesterol ester transport protein. They also play an important role in fatty acid metabolism by activating the sterol regulatory element-binding protein 1c gene. Here, we identify human LXRalpha (hLXRalpha) as an autoinducible gene. Induction in response to LXR ligands is observed in multiple human cell types including macrophages and occurs within 2--4 h. Analysis of the hLXRalpha promoter revealed three LXR response elements (LXREs); one exhibits strong affinity for both LXRalpha:RXR and LXRbeta:RXR (a type I LXRE), and deletion and mutational studies indicate it plays a critical role in LXR-mediated induction. The other two LXREs are identical to each other, exist within highly conserved Alu repeats, and exhibit selective binding to LXRalpha:RXR (type II LXREs). In transfections, the type I LXRE acts as a strong mediator of both LXRalpha and LXRbeta activity, whereas the type II LXRE acts as a weaker and selective mediator of LXRalpha activity. Our data suggest a model in which LXR ligands trigger an autoregulatory loop leading to selective induction of hLXRalpha gene expression. This would lead to increased hLXRalpha levels and transcription of its downstream target genes such as ABCA1, providing a simple yet exquisite mechanism for cells to respond to LXR ligands and cholesterol loading.

Age and Sex Dependency of Carnitine Concentration in Human Serum and Skeletal Muscle

Carnitine plays an essential role in fatty acid metabolism. It can be synthesized in the liver, but additional intestinal resorption is necessary (1). Carnitine mediates the transport of activated acyl residues via the carnitine palmityl transferase system into mitochondria for β-oxidation (2). Whereas primary carnitine deficiency is attributable to mutations in OCTN2 [a carnitine transporter of plasma membranes (3)], several other conditions can cause secondary deficiency (4). The leading symptom of either primary or secondary carnitine deficiency is weakness of skeletal muscles. In addition to these pathologic conditions in some animal models, a physiologic decline of carnitine concentration with aging has been reported (5)(6). In addition to increasing muscular carnitine concentrations (6), oral treatment with l-carnitine or its acetyl ester has also been shown to restore many of physiologic impairments that accompany aging (7)(8)(9)(10). These data indicate the important role of carnitine in the aging process, at least in mice and rats. For human skeletal muscle, confusing results exist with respect to the age dependency of carnitine content: Whereas Costell et al. (5) found a “drastic” age-dependent decrease of carnitine in human skeletal muscle and Gonzalez-Crespo et al. (11) detected reduced free carnitine concentrations in elderly patients undergoing hip surgery, an age-dependent decrease in carnitine concentration could not be confirmed by Starling et al. (12). The answer to the question of whether carnitine in human muscle is also age dependent is hampered by the different populations investigated and the different methods used. No reliable data exist concerning the sex dependency of a possible age-dependent variation. The present study seeks to clarify whether carnitine concentrations in human skeletal muscle and serum depend on age and sex. The physiologic relevance is discussed. Analysis of carnitine in serum was performed in samples from healthy …

Genomic organization and transcription units of the human acyl-CoA synthetase 3 gene

Acyl-CoA synthetases (ACSs) play an essential role in fatty acid metabolism. ACS3 is an arachidonate-preferring enzyme expressed in a wide range of human tissues including brain, heart, placenta, prostate, skeletal muscle, testis and thymus. As an initial step to understanding the transcriptional regulation of the human ACS3 gene, we analyzed the genomic organization and transcription units of the human ACS3 gene. Sequence analysis of genomic clones demonstrates that the human ACS3 gene spans at least 80.6 kb and contains 17 exons. The human ACS3 gene was mapped between the sequence-tagged site markers D2S360 and WI-21901. Sequence inspection of the 5′-flanking region revealed potential DNA elements including CCAAT, AP-1, Oct-1, GATAs, SRY, CdxA, Nkx-2.5, c-Myb, HSF2, NF-AT, AP-2, NF-Y, and p300. A minimal promoter region required for the expression of the human ACS3 gene in melanoma G361 cells was determined.

Binding site differences revealed by crystal structures of Plasmodium falciparum and bovine acyl-CoA binding protein

Acyl-CoA binding protein (ACBP) maintains a pool of fatty acyl-CoA molecules in the cell and plays a role in fatty acid metabolism. The biochemical properties of Plasmodium falciparum ACBP are described together with the 2.0 Å resolution crystal structures of a P. falciparum ACBP-acyl-CoA complex and of bovine ACBP in two crystal forms. Overall, the bovine ACBP crystal structures are similar to the NMR structures published previously; however, the bovine and parasite ACBP structures are less similar. The parasite ACBP is shown to have a different ligand-binding pocket, leading to an acyl-CoA binding specificity different from that of bovine ACBP. Several non-conservative differences in residues that interact with the ligand were identified between the mammalian and parasite ACBPs. These, together with measured binding-specificity differences, suggest that there is a potential for the design of molecules that might selectively block the acyl-CoA binding site.

Physiological and pharmacological function of PPARs

The finding of nuclear receptors has greatly enhanced our understanding of gene regulation by lipophilic hormones such as steroids, thyroxine, vitamin D and retinoids. These receptors comprise a superfamily of transcription factors containing highly related DNA-binding domains. In mammals, the peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors consists of three subtypes by separate genes: PPAR alpha, PPAR delta (also referred to as hNUC1 or PPAR beta), and PPAR gamma. PPARs have been associated with several distinct biological programs. PPARs function as a heterodimer with the retinoid X receptor. This complex binds to sequences termed direct repeat-1 response element in enhancer sites of regulated genes and activates transcription upon ligand and coactivator binding. Three different PPAR subtypes have specific roles in different organs. PPAR alpha, mainly expressed in liver, plays an important role in fatty acid metabolism. PPAR gamma predominantly is expressed in adipose cells. PPAR delta displays a high level of expression in lipid-metabolizing organs such as small intestine, heart and adipose tissue. Naturally occurring and synthetic molecules (anti-hyperlipidemia and diabetic drugs) that are ligands for these nuclear receptors control transcriptional activity of PPARs. We believe that the pharmacological and genomic researches on PPAR will develop powerful tools for prevention and medical care against common diseases.

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.

Role of fatty acid metabolism in hepatocyte proliferation

Role of fatty acid metabolism in hepatocyte proliferation