Showing papers on "Acyl-CoA published in 1998"
TL;DR: An expressed sequence tag clone that shared regions of similarity with acyl CoA:cholesterol acyltransferase, an enzyme that also uses fatty acyl coA as a substrate was identified, which will greatly facilitate studies of cellular glycerolipid metabolism and its regulation.
Abstract: Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells Acyl CoA:diacylglycerol acyltransferase (DGAT, EC 23120) catalyzes the terminal and only committed step in triacylglycerol synthesis, by using diacylglycerol and fatty acyl CoA as substrates DGAT plays a fundamental role in the metabolism of cellular diacylglycerol and is important in higher eukaryotes for physiologic processes involving triacylglycerol metabolism such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation DGAT is an integral membrane protein that has never been purified to homogeneity, nor has its gene been cloned We identified an expressed sequence tag clone that shared regions of similarity with acyl CoA:cholesterol acyltransferase, an enzyme that also uses fatty acyl CoA as a substrate Expression of a mouse cDNA for this expressed sequence tag in insect cells resulted in high levels of DGAT activity in cell membranes No other acyltransferase activity was detected when a variety of substrates, including cholesterol, were used as acyl acceptors The gene was expressed in all tissues examined; during differentiation of NIH 3T3-L1 cells into adipocytes, its expression increased markedly in parallel with increases in DGAT activity The identification of this cDNA encoding a DGAT will greatly facilitate studies of cellular glycerolipid metabolism and its regulation
1,117 citations
TL;DR: It is shown that long-chain fatty acids directly modulate the transcriptional activity of HNF-4α by binding as their acyl-CoA thioesters to the ligand-binding domain of H NF-4 α.
Abstract: Dietary fatty acids specifically modulate the onset and progression of various diseases, including cancer, atherogenesis, hyperlipidaemia, insulin resistances and hypertension, as well as blood coagulability and fibrinolytic defects; their effects depend on their chain length and degree of saturation Hepatocyte nuclear factor-4alpha (HNF-4alpha) is an orphan transcription factor of the superfamily of nuclear receptors and controls the expression of genes that govern the pathogenesis and course of some of these diseases Here we show that long-chain fatty acids directly modulate the transcriptional activity of HNF-4alpha by binding as their acyl-CoA thioesters to the ligand-binding domain of HNF-4alpha This binding may shift the oligomeric-dimeric equilibrium of HNF-4alpha or may modulate the affinity of HNF-4alpha for its cognate promoter element, resulting in either activation or inhibition of HNF-4alpha transcriptional activity as a function of chain length and the degree of saturation of the fatty acyl-CoA ligands In addition to their roles as substrates to yield energy, as an energy store, or as constituents of membrane phospholipids, dietary fatty acids may affect the course of a disease by modulating the expression of HNF-4alpha-controlled genes
517 citations
Journal Article•
TL;DR: In this article, the first part in a series of three articles about fat metabolism during exercise is discussed. In this part the mobilization of fatty acids and their metabolism will be discussed as well as the possible limiting steps of fat oxidation.
Abstract: This is the first part in a series of three articles about fat metabolism during exercise. In this part the mobilization of fatty acids and their metabolism will be discussed as well as the possible limiting steps of fat oxidation. It is known for a long time that fatty acids are an important fuel for contracting muscle. After lipolysis, fatty acids from adipose tissue have to be transported through the blood to the muscle. Fatty acids derived from circulating TG may also be used as a fuel but are believed to be less important during exercise. In the muscle the IMTG stores may also provide fatty acids for oxidation after stimulation of hormone sensitive lipase. In the muscle cell, fatty acids will be transported by carrier proteins (FABP), and after activation, fatty acyl CoA have to cross the mitochondrial membrane through the carnitine palmytoyl transferase system, after which the acyl CoA will be degraded to acetyl CoA for oxidation. The two steps that are most likely to limit fat oxidation are fatty acid mobilization from adipose tissue and transport of fatty acids into the mitochondria along with mitochondrial density and the muscles capacity to oxidize fatty acids.
117 citations
TL;DR: The two steps that are most likely to limit fat oxidation are fatty acid mobilization from adipose tissue and transport of fatty acids into the mitochondria along with mitochondrial density and the muscles capacity to oxidize fatty acids.
Abstract: This is the first part in a series of three articles about fat metabolism during exercise. In this part the mobilization of fatty acids and their metabolism will be discussed as well as the possible limiting steps of fat oxidation. It is known for a long time that fatty acids are an important fuel for contracting muscle. After lipolysis, fatty acids from adipose tissue have to be transported through the blood to the muscle. Fatty acids derived from circulating TG may also be used as a fuel but are believed to be less important during exercise. In the muscle the IMTG stores may also provide fatty acids for oxidation after stimulation of hormone sensitive lipase. In the muscle cell, fatty acids will be transported by carrier proteins (FABP), and after activation, fatty acyl CoA have to cross the mitochondrial membrane through the carnitine palmytoyl transferase system, after which the acyl CoA will be degraded to acetyl CoA for oxidation. The two steps that are most likely to limit fat oxidation are fatty acid mobilization from adipose tissue and transport of fatty acids into the mitochondria along with mitochondrial density and the muscles capacity to oxidize fatty acids.
105 citations
TL;DR: In this paper, a steady state, photon counting fluorescence spectroscopy directly established that rat liver ACBP bound 18-carbon cis-and trans-parinaroyl-CoA, K d = 7.03 ± 0.95 and 4.40± 0.43 nm, respectively.
66 citations
Patent•
05 Jun 1998TL;DR: In this paper, nucleic acid sequences encoding for fatty acyl-CoA: fatty alcohol acyltransferase (wax synthase) are provided, wherein said wax synthase is active in the formation of a wax ester from fatty alcohol and co-A substrates.
Abstract: By this invention, nucleic acid sequences encoding for fatty acyl-CoA: fatty alcohol acyltransferase (wax synthase) are provided, wherein said wax synthase is active in the formation of a wax ester from fatty alcohol and fatty acyl-CoA substrates. Of special interest are nucleic acid sequences obtainable from a jojoba embryo wax synthase having an apparent molecular mass of approximately 33kD. Also considered are amino acid and nucleic acid sequences obtainable from wax synthase proteins and the use of such sequences to provide transgenic host cells capable of producing wax esters.
55 citations
TL;DR: The recent cloning of a human cDNA for ACAT, together with genome sequencing projects, has led to the identification of an ACAT gene family and provided molecular tools for determining ACAT's functions in vivo.
Abstract: Acyl coenzyme A:cholesterol acyltransferase (ACAT) (EC 23126) is an enzyme, located in the endoplasmic reticulum of many types of cells, that catalyzes cholesterol ester formation from cholesterol and fatty acyl CoA substrates Sterol esterification by ACAT or homologous enzymes is conserved in evolution dating back to yeast The recent cloning of a human cDNA for ACAT, together with genome sequencing projects, has led to the identification of an ACAT gene family and provided molecular tools for determining ACAT's functions in vivo Summarized here is the current knowledge concerning the molecular genetics of ACAT
40 citations
TL;DR: The notion that changes in malonyl CoA contribute to the increases in long chain fatty acyl CoA, (LCFA CoA), diacylglycerol and triglyceride content and changes in protein kinase C activity and distribution observed in insulin-resistant muscle is reviewed.
Abstract: Malonyl CoA is an inhibitor of carnitine palmitoyl transferase 1 (CPT1), the enzyme that regulates the transfer of long chain fatty acyl CoA into mitochondria. By virtue of this effect, it is thought to play a key role in regulating fatty acid oxidation. Thus, when the supply of glucose to muscle is increased, malonyl CoA levels increase in keeping with a decreased need for fatty acid oxidation, and fatty acids are preferentially esterified to form diaglycerol and triglycerides. In contrast, during exercise, when the need for fatty acid oxidation is increased, malonyl CoA levels fall. Changes in glucose supply regulate malonyl CoA by modulating the concentration of cytosolic citrate, an allosteric activator of acetyl CoA carboxylase (ACC), the rate-limiting enzyme for malonyl CoA formation and a precursor of its substrate cytosolic acetyl CoA. Conversely, exercise lowers the concentration of malonyl CoA, by activating an AMP-activated protein kinase, which phosphorylates and inhibits ACC. A number of reports have linked sustained increases in the concentration of malonyl CoA in muscle to insulin resistance. In this paper, we review these reports, as well as the notion that changes in malonyl CoA contribute to the increases in long chain fatty acyl CoA, (LCFA CoA), diacylglycerol and triglyceride content and changes in protein kinase C activity and distribution observed in insulin-resistant muscle. We also review the implications of the malonyl CoA/LCFA CoA hypothesis to two other proposed mechanisms for insulin resistance, the glucose-fatty acid cycle and the hexosamine theory.
40 citations
TL;DR: It is demonstrated that purified rabbit brain PKC undergoes specific acylation with palmitoyl CoA that facilitates its interaction with membrane bilayers and identifies a novel mechanism which may facilitate the interaction of PKC with biologic membranes.
Abstract: Protein kinase C (PKC) translocation to specific subcellular membrane loci after cellular stimulation is mediated, in part, through its interaction with diacylglycerol, phosphatidylserine, and calcium. Herein, we present multiple lines of evidence which demonstrate that purified rabbit brain PKC undergoes specific acylation with palmitoyl CoA that facilitates its interaction with membrane bilayers. First, incubation of purified rabbit brain PKC with [14C]palmitoyl CoA (5 μM) resulted in the radiolabeling of an 80 kDa band demonstrated by SDS−PAGE and autoradiography, while incubation of PKC with other acyl CoA molecular species (e.g., [3H]myristoyl CoA or [14C]arachidonoyl CoA), fatty acids (e.g., [14C]palmitic and [14C]arachidonic acid), or [14C]diacylglycerol did not result in the incorporation of radiolabel. Second, multiple extractions of [14C]palmitoyl CoA-treated PKC with butanol did not remove the radiolabeled moiety from the 80 kDa PKC band. Third, incubation of the [14C]palmitoyl CoA-radiolabeled...
22 citations
Patent•
19 Feb 1998
TL;DR: A bacterial gene which encodes an enzyme that is an acyl-CoA reductase was identified in this article, which is able to chemically reduce acyl CoAs to their corresponding alcohols via aldehyde intermediates.
Abstract: A bacterial gene which encodes an enzyme that is an acyl-CoA reductase. The acyl-CoA reductase is able to chemically reduce acyl-CoAs to their corresponding alcohols, via aldehyde intermediates.
22 citations
TL;DR: Martin et al. as discussed by the authors reported a general synthetic approach to analogues of coenzyme A (CoA) and CoA esters using a combination of enzymatic and nonenzymatic reactions.
Abstract: We have previously reported a general synthetic approach to analogues of coenzyme A (CoA) and CoA esters using a combination of enzymatic and nonenzymatic reactions (Martin et al. J. Am. Chem. Soc....
TL;DR: It is concluded that the ligand acyl-CoA is bound via its acyl chain, which is potentially useful for the identification and purification of this specific acyltransferase.
TL;DR: It is established that the enzymes involved in turnover of arachidonic acid in phospholipids are present in tissues in the non-pregnant and pregnant guinea-pig uterus.
Abstract: Acyl-CoA synthetase (ACS), acyl-CoA:lysophospholipid acyltransferase (ACLAT) and phospholipase (PL) A2 activities were detected in guinea-pig endometrium on days 7 and 15 of the cycle, and on days 15, 29 and 36 of pregnancy. Ovariectomy of non-pregnant animals resulted in an increase in the apparent activities of these three enzymes which was reversed by treatment with oestradiol and/or progesterone. ACS, ACLAT and PLA2 activities were detected in day 15 conceptuses, and in the placenta, sub-placenta, chorion and amnion on days 29 and 36 of pregnancy. Apparent activities of the enzymes were generally higher in the fetal membranes than in the placental tissue. This study has established that the enzymes involved in turnover of arachidonic acid in phospholipids are present in tissues in the non-pregnant and pregnant guinea-pig uterus. The higher apparent activities of enzymes (ACS and ACLAT) involved in arachidonic acid uptake compared to the enzyme (PLA2) involved in arachidonic acid release is in agreement with there being very low concentrations of free arachidonic acid in tissues.
TL;DR: The data indicate that this new photoaffinity label may have application to identify and characterize lipid biosynthetic enzymes using unsaturated fatty acids as well as acyl-CoA binding proteins and the active site of these proteins.
01 Jan 1998
TL;DR: An expressed sequence tag clone that shared regions of similarity with acyl CoA:cholesterol acyltransferase, an enzyme that also uses fatty acyl coA as a substrate was identified, which will greatly facilitate studies of cellular glycerolipid metabolism and its regulation.
Abstract: Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells. Acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) cat- alyzes the terminal and only committed step in triacylglycerol synthesis, by using diacylglycerol and fatty acyl CoA as substrates. DGAT plays a fundamental role in the metabolism of cellular diacylglycerol and is important in higher eu- karyotes for physiologic processes involving triacylglycerol metabolism such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation. DGAT is an integral membrane protein that has never been purified to homogeneity, nor has its gene been cloned. We identified an expressed sequence tag clone that shared regions of similarity with acyl CoA:cholesterol acyltransferase, an enzyme that also uses fatty acyl CoA as a substrate. Expression of a mouse cDNA for this expressed sequence tag in insect cells resulted in high levels of DGAT activity in cell membranes. No other acyltransferase activity was detected when a variety of sub- strates, including cholesterol, were used as acyl acceptors. The gene was expressed in all tissues examined; during differen- tiation of NIH 3T3-L1 cells into adipocytes, its expression increased markedly in parallel with increases in DGAT activ- ity. The identification of this cDNA encoding a DGAT will greatly facilitate studies of cellular glycerolipid metabolism and its regulation.
01 Jan 1998
TL;DR: The recent research that has led to the identification and characterization of two mammalian ACAT enzymes, ACAT-1 and ACat-2, are reviewed.
Abstract: The formation of sterol esters from free sterols and fatty acyl CoAs is a fundamental pathway in lipid metabolism of eukaryotic cells. In vertebrates, the sterol esterification reaction is catalyzed by acyl CoA:cholesterol acytransferase (ACAT; EC 2.3.1.26), an enzyme located primarily in the endoplasmic reticulum. In addition to its role in cellular cholesterol homeostasis, ACAT has been hypothesized to participate in a number of processes involving mammalian cholesterol metabolism. Recent studies have provided evidence that more than one ACAT enzyme exists in mammals. Here we review the recent research that has led to the identification and characterization of two mammalian ACAT enzymes, ACAT-1 and ACAT-2.