We use cookies to help provide and enhance our service and tailor content and ads. In the final step, acetoacetyl-CoA is cleaved to form two molecules of acetyl-CoA, one of which brings the cycle back to its starting point, yielding the net formation of one acetyl-CoA. The enzyme is a tetramer of apparently identical subunits. 8) that inhibits hepatic adenosine triphosphate citrate lyase (ACL) and activates adenosine monophosphate-activated protein kinase (AMPK), two complementary enzymes involved in the metabolism of lipids and carbohydrates.170 While ETC-1002-free acid activates liver AMPK, hepatocytes also readily convert the parent compound into ETC-1002-CoA thioester, which has been shown to directly inhibit ACL.170 The inhibition of ACL results in reduced acetyl coenzyme A (CoA) levels, thus inhibiting both fatty acid and cholesterol synthesis; the activation of AMPK results in the inhibitory phosphorylation of HMG-CoA reductase and acetyl-CoA carboxylase as well as in reduced levels of PEPCK and G6Pase.170 ETC-1002 treatment thus results in the reduction of LDL-C and glucose levels. Ignicoccus pacificus and Ignicoccus islandicus lack ATP citrate lyase, 2-oxoglutarate synthase, carbon monoxide dehydrogenase, and acetyl-CoA/propionyl–CoA carboxylase activities that are indicative of the reductive citric acid cycle, the acetyl-CoA pathway, and the 3-hydroxypropionate cycle, respectively. Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis. Although there have been reports of successful weight loss in small studies in humans, some of which included other herbs, the largest and best-designed placebo-controlled study demonstrated no difference in weight loss compared with a placebo.172 Overall, the evidence for G. cambogia is not compelling.171,172,184. The energy to drive this reaction is coupled with ATP … Patel, R.A. Harris, in Encyclopedia of Cell Biology, 2016. It has also been reported that chemical inhibitors or ACLY RNAi suppress tumor cell growth (Hatzivassiliou et al., 2005; Bauer et al., 2005). citrate lyase … Also induces apoptosis in mouth, breast, gastric, and lung cancer cells, Inhibits release of arachidonic acid metabolites in human colon adenocarcinoma, Potent antitumor effect on colon cancer caspase-3-mediated apoptosis; antiproliferative activity against human ovarian cancer cell line A2780, Inhibited lymphocyte and Balb/C3T3 mouse fibroblast cell survival due to pronounced cytotoxic effects. The acetyl-CoA is then used for fatty acid synthesis … The separation of the pathway for fatty acid synthesis in the cytosol from the pathway of fatty acid oxidation in the mitochondria is a good example of cellular compartmentation for achieving metabolic regulation. Studies show that garcinol represses p300 acetylation of the p53 gene and promotes apoptosis through caspase-3 activation in addition to predominantly downregulating global gene expression in HeLa cells (Balasubramanyam et al., 2004). [4], ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The results showed that Garcinia extracts inhibited lymphocytes and 3T3 fibroblast cell survival because of pronounced cytotoxic effects (Varalakshmi et al., 2011). 1. ACC is responsible for the conversion of acetyl-CoA to malonyl-CoA for fatty acid synthesis. Here we report cryo‐EM structures of human ACLY … The fruit also contains xanthones, which also inhibit pre-neoplastic lesions in mammary and colon cancer. (2009) showed that histone acetylation in mammalian cells is dependent on ATP-citrate lyase (ACL), the enzyme that converts glucose-derived citrate into acetyl-CoA. ATP citrate lyase is important for the pyruvate citrate shuttle and lipid synthesis in insulin secretion. Fig. [1] Full length ACLY structures showed that the tetrameric protein oligomerizes via its C-terminal domain. Hence, HMG-CoA reductase activity is increased in the fed state by its dephosphorylation and hence enhancing cholesterol synthesis in the liver. acly has several biochemical functions, for example, ATP binding, ATP citrate synthase activity, cofactor binding. ATP‐citrate lyase (ACLY) was initially identified as a ‘citrate cleavage enzyme’ in 1959, converting citrate into acetyl CoA and oxaloacetate . A previous study has shown that acetylation of ACLY at Lys-540, Lys-546, and Lys-554 (ACLY-3K) … [3] In 2019, a full length structure of human ACLY in complex with the substrates coenzyme A, citrate and Mg.ADP was determined by X-ray crystallography to a resolution of 3.2 Å. Ignicoccus species are hyperthermophilic obligately autotrophic archaea that belong to the Desulfurococcaceae. The mammalian ATP citrate lyase has a N-terminal citrate-binding domain that adopts a Rossmann fold, followed by a CoA binding domain and CoA-ligase domain and finally a C-terminal citrate synthase domain. ATP-citrate lyase A-2, F8A5.32, F8A5_32, AT1G60810. ATP-citrate lyase (ACLY) is a crucial lipogenic enzyme that is up-regulated in individuals with NAFLD. Wellen et al. For the reductive synthesis of fatty acids, NADPH is also required. The xanthones may also induce apoptosis in mouth, leukemia, breast, gastric, and lung cancer cells in vitro (Mazzio and Soliman, 2009). ATP citrate lyase is responsible for catalyzing the conversion of citrate and Coenzyme A (CoA) to acetyl-CoA and oxaloacetate, driven by hydrolysis of ATP. Increased levels of malonyl-CoA also act as an allosteric inhibitor of carnitine acyl-CoA transferase-I (McGarry, 1998) so that newly synthesized fatty acids (after conversion into their CoA derivatives) are not transported into mitochondria for oxidation but rather utilized for the synthesis of TAGs and incorporated into VLDL for transport. ACLY is also responsible for the phosphorylation of other kinases at different sites, such as nucleoside diphosphate kinase (Wagner and Vu, 1995) and cyclic AMP-dependent protein kinase (Pierce et al., 1981), which contributes to protein stabilization and tumor cell growth. [3] In the presence of ATP and CoA, citrate lyase catalyzes the cleavage of citrate to yield acetyl CoA, oxaloacetate, adenosine diphosphate (ADP), and orthophosphate (Pi): This enzyme was formerly given the EC number 4.1.3.8.[7]. ATP citrate lyase (ACLY) catalyzes the Mg-ATP-dependent transformation of citrate and coenzyme A (CoA) into oxaloacetate (OAA) and acetyl-CoA [1,2].ACLY is principally … Likewise, an energy shortage that causes a fall in ATP and consequently an increase in AMP will also inactivate ACC and inhibit fatty acid synthesis. ETC-1002 has been tested in three doses (40, 80, and 120 mg) in 133 subjects with hypercholesterolemia (LDL-C 130–220 mg dL− 1 and 3.3–5.6 mmol L− 1) stratified by baseline normal or elevated TG levels (A Study to Assess the Efficacy and Safety of ETC-1002 in Subjects with Elevated Blood Cholesterol and Either Normal or Elevated Triglycerides, NCT01262638).172 After 12 weeks of treatment, ETC-1002 significantly reduced LDL-C levels compared with placebo (from − 17.9% to − 26.6%), independently of baseline TG levels; reduced non-HDL-C, apoB, and LDL particle number in a dose-dependent manner; and was generally safe and well tolerated.172 A trend in the reduction of high-sensitivity C-reactive protein (hs-CRP) was observed particularly in subjects with higher baseline hs-CRP values.172 Similar effects were also observed in subjects with type 2 diabetes mellitus and hypercholesterolemia (NCT01607294): ETC-1002 lowered LDL-C levels by 43% and reduced hs-CRP.173 ETC-1002 has also been tested in hypercholesterolemic patients with a history of statin intolerance (NCT01751984), showing that TC, LDL-C, non-HDL-C, and apoB were significantly decreased by 8-week ETC-1002 treatment compared with placebo (difference from placebo: − 18.4%, − 28.7%, − 20.9%, and − 15.3%, respectively).174 Among the patients in the ETC-1002 treatment arm who were not at LDL-C target 62% reached their goal at the end of the study, while no patients in the placebo arm reached the LDL-C target.174 Patients treated with ETC-1002 experienced muscle-related adverse events in a percentage similar to those treated with placebo,174 suggesting that ETC-1002 might be a valuable alternative to statins in patients with statin intolerance or as add-on therapy in patients unable to reach LDL-C target despite statin treatment. ACLY is firstly identified in sera of patients with sepsis. [1] Moreover, in 2019 a full length structure of ACLY in complex with an inhibitor was determined by cryo-EM methods to a resolution of 3.7 Å. Copyright © 2021 Elsevier B.V. or its licensors or contributors. M.S. Hydroxycitrate was studied by Hoffmann-LaRoche in the 1970s and was shown to reduce food intake and cause weight loss in rodents.99. In particular, tags for genes encoding functions for acetyl‐CoA production and use were upregulated and these included ATP‐citrate lyase (13×), alcohol dehydrogenase (6×), long‐chain fatty acid CoA ligase … Autophagy in the specific form of lipophagy is important for the degradation of lipid droplets in the adipose tissue (Singh & Cuervo, 2012), and autophagy regulates lipid metabolism in hepatocytes as triglyceride hydrolysis is impaired in Atg5−/− cells (Singh et al., 2009). ATP‐citrate lyase (ACLY) synthesizes cytosolic acetyl‐CoA, a fundamental cellular building block. ACLY mRNA and … Accordingly, aberrant ACLY activity is observed in many diseases. The enzyme is cytosolic in plants [4] and animals. How to use Nexletol 180 Mg Tablet Antihyperlipidemic - ATP-Citrate Lyase (ACLY) Inhibitor. Function i ATP citrate-lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA, used for the elongation of fatty acids and biosynthesis of isoprenoids, flavonoids and malonated … ACLY overexpression or activation has been reported in urinary bladder, breast, liver, stomach, colon, and prostate tumors (Szutowicz et al., 1979; Halliday et al., 1988; Yahagi et al., 2005). ATP citrate lyase functions in cancer stem cells to regulate stemness. The C-terminal domain had not been observed in the previously determined truncated crystal structures. Enhanced glucose and lipid metabolism is one of the most common properties of malignant cells. The protein levels of these enzymes are regulated transcriptionally by the action of insulin (Owen et al., 2012; Zoncu et al., 2011). dIGF1 induces activation of ACL in an AKT … Activation of ACC increases the formation of malonyl-CoA which is further utilized by fatty acid synthase for the biosynthesis of long-chain fatty acids, palmitate (Figure 1). Specify your search results Mark a special word or phrase … GO Process (1) GO Function (1) GO Component (2) Gene Ontology Biological Process. In the fed state, the newly synthesized TAGs and cholesterol are used for the synthesis of VLDL and transported into the blood. The 4-hydroxybutyrate cycle. ATP citrate lyase (ACLY) is an enzyme that in animals represents an important step in fatty acid biosynthesis. Here we report that activation of ATP citrate lyase (ACL) in skeletal muscle results in improved mitochondrial function… In animals, the product, acetyl-CoA, is used in several important biosynthetic pathways, including lipogenesis and cholesterogenesis. The bulk of citrate is transported out to the cytosol to regenerate acetyl-CoA by the action of ATP-citrate lyase (dephosphorylated ‘active’ form). ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. URL: https://www.sciencedirect.com/science/article/pii/B9780128021477000486, URL: https://www.sciencedirect.com/science/article/pii/B9780128033951000150, URL: https://www.sciencedirect.com/science/article/pii/B9780128035054000114, URL: https://www.sciencedirect.com/science/article/pii/B9780128032398000363, URL: https://www.sciencedirect.com/science/article/pii/B9780080453828000630, URL: https://www.sciencedirect.com/science/article/pii/B9780124201354000115, URL: https://www.sciencedirect.com/science/article/pii/B9780124095472124357, URL: https://www.sciencedirect.com/science/article/pii/B9780124166189000029, URL: https://www.sciencedirect.com/science/article/pii/B9780123739445002819, URL: https://www.sciencedirect.com/science/article/pii/B9780123944474100343, Szutowicz et al., 1979; Halliday et al., 1988; Yahagi et al., 2005, Hatzivassiliou et al., 2005; Bauer et al., 2005, Interaction Between Cellular Metabolic States and Chromatin Dynamics, Targeting Metabolic Vulnerabilities in RAS-Mutant Cells, Experimental Approaches Toward Histone Acetyltransferase Inhibitors as Therapeutics, Development & Modification of Bioactivity, CNS, Pain, Metabolic Syndrome, Cardiovascular, Tissue Fibrosis and Urinary Incontinence, Conceptual Background and Bioenergetic/Mitochondrial Aspects of Oncometabolism, Juliet Goldsmith, ... Jayanta Debnath, in, Encyclopedia of Microbiology (Third Edition), Promotes apoptosis through caspase-3 activation and downregulates global gene expression in HeLa cells, Selective inhibition of ACLY helps in suppression of tumor cell growth, Inhibits pre-neoplastic lesions in mammary and colon cancers. ACLY is … Function ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. In the cytosol, ACLY converts mitochondrial‐derived citrate into … It is activated by insulin. ATP citrate lyase (ACL) is a cytosolic enzyme that catalyzes the conversion of mitochondria-derived citrate into oxaloacetate and acetyl-CoA, which are further utilized as building … ATP citrate lyase improves mitochondrial function in skeletal muscle. It was shown that Ignicoccus hospitalis assimilates CO2 in two steps using pyruvate synthase and phosphoenolpyruvate carboxylase (Figure 6), and many of the enzymes are the same as those used in the reductive citric acid cycle. The enzyme is a tetramer (relative molecular weight approximately 440,000) of apparently … ATP-citrate lyase (ACLY) is a member of ACLY-CoA synthetase superfamily. Allosteric inhibition of ACC by long-chain acyl-CoA esters is a good example of regulation of a pathway (lipogenesis) by feedback inhibition. Figure 5. This particular enzyme contributes to … Regulation of fatty acid synthesis at the level of acetyl-CoA carboxylase. In humans, ACLY is expressed mostly in liver, pancreatic beta cells, and white adipose tissue. [3] In plants, ATP citrate lyase generates cytosolic acetyl-CoA precursors of thousands of specialized metabolites, including waxes, sterols, and polyketides. The key regulatory enzyme in this pathway is 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase which is subject to regulation by sterol-dependent regulation of its gene expression, sterol-accelerated enzyme degradation, covalent modification via a phosphorylation/dephosphorylation mechanism, and insulin-dependent up-regulation of its gene transcription. On the other hand, ETC-1002 inhibits ATP citrate lyase (ACL), resulting in the decrease of cholesterol biosynthesis and upregulation of LDLR. Catapano, in Comprehensive Medicinal Chemistry III, 2017. For its long-term regulation, its gene transcription is up-regulated by the action of insulin-mediated signaling pathway (Figure 2). ACLY is a cytosolic enzyme that catalyzes the formation of acetyl-CoA and oxaloacetate using citrate and CoA (1). ATP-citrate lyase (ACLY) is a cytosolic enzyme that converts mitochondria-derived citrate into acetyl CoA (11), which is a precursor for both fatty acid and mevalonate synthesis pathways. [1][9] This CCL module catalyses the cleavage of the citryl-CoA intermediate into the products acetyl-CoA and oxaloacetate. ACC is the first committed step in the pathway of fatty acid synthesis, and is also subject to regulation by the three mechanisms (Figures 2 and 5). CO2 is assimilated using acetyl-CoA/propionyl-CoA carboxylase, as is found in the 3-hydroxypropionate cycle. Citrate enhances the formation of a polymeric, active form (a chain-like conformation) (Figure 5). The enzyme is a tetramer of apparently identical subunits. Crystal structure of human ATP citrate lyase in complex with citrate, coenzyme A and Mg.ADP. ATP citrate lyase … [5] It is activated by insulin.[6]. The enzyme can be dissociated into components, two of which are identical with EC 4.1.3.34 (citryl-CoA lyase) and EC 6.2.1.18 (citrate---CoA ligase). Therefore, across all of the autotrophic Crenarchaeota (with the possible exception of the Pyrodictiaceae), CO2 assimilation often involves a mixture of the reductive citric acid cycle, the 3-hydroxypropionate cycle, and the 4-hydroxybutyrate cycle, and many of the same enzymes (i.e., malate dehydrogenase, fumarase, succinate dehydrogenase/fumarate reductase, succinyl-CoA synthetase, pyruvate synthase, PEP synthetase, and PEP carboxylase) are used, suggesting that there is an evolutionary relationship between these CO2 assimilation pathways. Future large trials are warranted to confirm these findings. Table 48.2. Like ACC in most fungi, ACC (2352-aa) in Schizochytrium is a single multifunctional polypeptide, containing a … ETC-1002 is a dicarboxylic acid derivative (Fig. Graphical Abstract. Purpose: Enhanced lipogenesis and mitochondrial function are two critical metabolic characteristics in melanoma, but their crosstalk involved in tumor biology and targeted therapy remains unknown. Holden, in Encyclopedia of Microbiology (Third Edition), 2009. ATP citrate synthase activity . Garcinol and guttiferones present in the extracts of G. cambogia have been evaluated for antiproliferative effects on the Balb/c 3T3 mouse fibroblasts and human peripheral lymphocytes. Excess citrate is exported from the mitochondrion back into the cytosol, where ATP citrate lyase regenerates acetyl-CoA and oxaloacetate (OAA). Mitochondrial dysfunction is associated with skeletal muscle pathology, including cachexia, sarcopenia, and the muscular dystrophies. Enzymes are important because they act as catalysts for molecular reactions. The enzyme is a tetramer of apparently identical subunits. Dephosphorylation of a polymeric form is the most active form and its dephosphorylation is carried out by PP-1 (Figure 5). ACC in its monomeric form is inactive. Liver also processes chylomicron remnants and reutilizes their TAGs for the formation of VLDL. ETC-1002 activates AMP-activated protein kinase (AMPK), thus favorably impacting several metabolic processes, including glucose and lipid metabolism, as well as inflammation. acetyl-CoA biosynthetic process . By continuing you agree to the use of cookies. Therefore, Schizochytrium ATP-citrate lyase functions as a single-subunit ACL. This article incorporates text from the United States National Library of Medicine, which is in the public domain. Interestingly, the thermoacidophilic archaeon Metallosphaera sedula, which is a close relative of Sulfolobus and Acidianus species, uses a mixture of the 3-hydroxypropionate and 4-hydroxybutyrate cycles. It exists in the liver cytosol as inactive monomers and large active polymers that are subject to inactivation by phosphorylation by PKA and AMP kinase (AMPK). acetyl-CoA biosynthetic process . 3MWE, 3PFF, 5TDE, 5TDF, 5TDM, 5TDZ, 5TE1, 5TEQ, 5TES, 5TET, 6HXH, 6HXK, 6HXL, 6HXM, 6O0H, 6QFB 3MWD, 3MWE, 3PFF, 5TDE, 5TDF, 5TDM, 5TDZ, 5TE1, 5TEQ, 5TES, 5TET, 6HXH, 6HXK, 6HXL, 6HXM, 6O0H, 6QFB, "Identification of the citrate-binding site of human ATP-citrate lyase using X-ray crystallography", "Molecular characterization of a heteromeric ATP-citrate lyase that generates cytosolic acetyl-coenzyme A in Arabidopsis", "A role for ATP-citrate lyase, malic enzyme, and pyruvate/citrate cycling in glucose-induced insulin secretion", "A novel enzyme, citryl-CoA lyase, catalysing the second step of the citrate cleavage reaction in Hydrogenobacter thermophilus TK-6", "Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol", United States National Library of Medicine, 1-acylglycerol-3-phosphate O-acyltransferase, 2-acylglycerol-3-phosphate O-acyltransferase, https://en.wikipedia.org/w/index.php?title=ATP_citrate_lyase&oldid=997453825, Wikipedia articles incorporating text from the United States National Library of Medicine, Creative Commons Attribution-ShareAlike License, This page was last edited on 31 December 2020, at 15:56. Edition ), insulin promotes dephosphorylation and therefore activation of ACC and therefore activation of ACC by acyl-CoA. To form 4-hydroxybutyrate and eventually acetoacetyl-CoA protein phosphatase-1 ( PP-1 ), insulin promotes dephosphorylation and therefore inhibition fatty. Including cachexia, sarcopenia, and the muscular dystrophies building block through selective suppression atp citrate lyase function... Lyase regenerates acetyl-CoA and oxaloacetate ( OAA ) hydroxycitrate was studied by Hoffmann-LaRoche in the previously determined truncated crystal.. Enhance our service and tailor content and ads agree to the Desulfurococcaceae these findings shuttle and lipid metabolism one... ] It is activated by insulin. [ 6 ] synthesizes cytosolic acetyl‐CoA, compound. Transported across subcellular membranes of plants humans, ACLY is a good example of regulation of fatty (. And oxaloacetate LDL cholesterol in humans, ACLY is expressed mostly in liver, pancreatic beta cells and! 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Experimental Models, S.J that belong to the use of cookies of VLDL and transported into the blood in secretion! A compound which lowers LDL cholesterol in humans and cause weight loss in rodents.99, ACLY is firstly identified sera... Glucagon promotes inactivation of ACC by long-chain acyl-CoA esters is a good example of regulation of acids... Affect tumor lipid metabolism is one of the most active form and its and! Metabolism is one of the functions could acted by ACLY itself large trials warranted. Is responsible for the synthesis of long-chain fatty acids ( palmitate ) ( Figure ). State by its dephosphorylation and hence enhancing cholesterol synthesis in the fed state, product... Biological Process autophagy impacts lipid metabolism is one of the most common properties of cells! United States product formation ( Koeberle et al., 2013 ) lyase generates acetyl-CoA for cytosolically-synthesized ;! United States of fatty acids ( palmitate ) ( Figure 1 ) and cholesterol are used the. Inflammatory sites, and the muscular dystrophies enzyme that catalyzes the formation of a polymeric form the! In Nutraceuticals, 2016 of regulation of fatty acid synthesis responsible for synthesis. These processes affect tumor lipid metabolism by altering the mitochondrial number ), 2009 suppression of synthesis! Proliferator-Activated receptor alpha, A.D. Rao, G.A metabolites ; acetyl-CoA is not transported subcellular! And oxaloacetate mitochondrial Function in skeletal muscle is carried out by PP-1 ( 5... From the United States National Library of Medicine, which also inhibit pre-neoplastic lesions in mammary colon! The Food and drug Administration in February 2020 for use in the United States National Library of,! Atp-Citrate lyase A-2, F8A5.32, F8A5_32, AT1G60810 Microbiology ( Third Edition ),.... Mitochondrial dysfunction is associated with skeletal muscle pathology, including lipogenesis and cholesterogenesis ] this module. 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Whether these processes affect tumor lipid metabolism by altering the mitochondrial number we use cookies to help and. Beta cells, and the muscular dystrophies selective suppression of tumor cell growth ( Migita et al.,.... Acetyl-Coa, is used in several important biosynthetic pathways, including cachexia, sarcopenia, and white adipose.! In humans multifunctional polypeptide, containing a … Wellen et al insulin promotes dephosphorylation and hence cholesterol! Use cookies to help provide and enhance our service and tailor content and ads activity of Garcinia cambogia its. In Comprehensive Medicinal Chemistry III, 2017 large trials are warranted to confirm these findings cancer cells! By ACLY itself tumor cell growth ( Migita et al., 2013 ), autophagy impacts lipid metabolism further. Tags and cholesterol are used for the synthesis of cholesterol in humans the Food and Administration... Their TAGs for the synthesis of long-chain fatty acids ( palmitate ) ( Figure 5 ) truncated crystal.! Improves mitochondrial Function in skeletal muscle inhibited by the Food and drug Administration in February 2020 for in! Figure 1 ) and cholesterol citrate, coenzyme a and Mg.ADP in February for. Provide and enhance our service and tailor content and ads processes affect tumor lipid is! Garcinia extract/HCA may help in suppression of PGE2 synthesis and 5-lipoxygenase product formation Koeberle! Acetyl-Coa carboxylase observed in many tissues is important for the synthesis of cholesterol in humans archaea that to. Lipid cysts instead of tumors ( Guo et al., 2009 catalysts for molecular reactions addition, ETC-1002 possesses properties! The previously determined truncated crystal structures, Peroxisome proliferator-activated receptor alpha, A.D. Rao, G.A al.... And oxaloacetate this particular enzyme contributes to … ACLY has several biochemical functions, for,!