Human Acetyl-CoA Carboxylase 2

Abstract

cDNA encoding the 280-kDa acetyl-CoA carboxylase 2 (ACC2) isoform was isolated from human liver using the polymerase chain reaction. Sequencing the cDNA revealed an open reading frame of 7,449 base pairs (bp) that encode 2,483 amino acids (M r 279,380). Using 5-kilobase pair cDNA clones as probes, we localized the gene encoding the 280-kDa human carboxylase to chromosome 12q23. When the cDNA of ACC2 was compared with that of ACC1, the nucleotide sequences and the predicted amino acid sequences had about 60 and 80% identity, respectively. Ser77 and Ser79, which were found to be critical for the phosphorylation and subsequent inactivation of rat ACC1 (Ser78 and Ser80 of human ACC1), are conserved in ACC2 and are represented as Ser219 and Ser221, respectively. On the other hand, Ser1200, which is also a phosphorylation site in rat ACC1 (Ser1201 of human ACC1), is not conserved in ACC2. The homology between the amino acid sequences of the two human carboxylases, however, is primarily found downstream of residues Ser78 and Ser81 in human ACC1 and their equivalents, that is Ser219 and Ser221 in ACC2, suggesting that the sequence of the first 218 amino acids at the N terminus of ACC2 represents a unique peptide that accounts, in part, for the variance between the two carboxylases. Using a cDNA probe (400 bp) that encodes the N-terminal amino acid residues of ACC2 in Northern blot analyses of different human and mouse tissues showed that ACC2 is predominantly expressed in liver, heart, and the skeletal muscles. Polyclonal antibodies raised against the N-terminal peptide (amino acid residues 1–220) reacted specifically and equally with human and rat ACC2 carboxylases, confirming the uniqueness of this N-terminal peptide and its conservation in animal ACC2. In addition, we present evidence for the presence of an isoform of ACC2 (M r 270,000) in human liver that differs from the 280-kDa ACC2 by the absence of 303 nucleotides that encode 101 amino acids in the region between Arg1114 and Asp1215. The regulation and physiological significance of the two ACC2 isoforms remain to be determined. cDNA encoding the 280-kDa acetyl-CoA carboxylase 2 (ACC2) isoform was isolated from human liver using the polymerase chain reaction. Sequencing the cDNA revealed an open reading frame of 7,449 base pairs (bp) that encode 2,483 amino acids (M r 279,380). Using 5-kilobase pair cDNA clones as probes, we localized the gene encoding the 280-kDa human carboxylase to chromosome 12q23. When the cDNA of ACC2 was compared with that of ACC1, the nucleotide sequences and the predicted amino acid sequences had about 60 and 80% identity, respectively. Ser77 and Ser79, which were found to be critical for the phosphorylation and subsequent inactivation of rat ACC1 (Ser78 and Ser80 of human ACC1), are conserved in ACC2 and are represented as Ser219 and Ser221, respectively. On the other hand, Ser1200, which is also a phosphorylation site in rat ACC1 (Ser1201 of human ACC1), is not conserved in ACC2. The homology between the amino acid sequences of the two human carboxylases, however, is primarily found downstream of residues Ser78 and Ser81 in human ACC1 and their equivalents, that is Ser219 and Ser221 in ACC2, suggesting that the sequence of the first 218 amino acids at the N terminus of ACC2 represents a unique peptide that accounts, in part, for the variance between the two carboxylases. Using a cDNA probe (400 bp) that encodes the N-terminal amino acid residues of ACC2 in Northern blot analyses of different human and mouse tissues showed that ACC2 is predominantly expressed in liver, heart, and the skeletal muscles. Polyclonal antibodies raised against the N-terminal peptide (amino acid residues 1–220) reacted specifically and equally with human and rat ACC2 carboxylases, confirming the uniqueness of this N-terminal peptide and its conservation in animal ACC2. In addition, we present evidence for the presence of an isoform of ACC2 (M r 270,000) in human liver that differs from the 280-kDa ACC2 by the absence of 303 nucleotides that encode 101 amino acids in the region between Arg1114 and Asp1215. The regulation and physiological significance of the two ACC2 isoforms remain to be determined. Acetyl-CoA carboxylase (ACC), 1The abbreviations used are: ACC, acetyl-CoA carboxylase; RACE, rapid amplification of cDNA ends; PCR, polymerase chain reaction; kb, kilobase(s); bp, base pair(s). 1The abbreviations used are: ACC, acetyl-CoA carboxylase; RACE, rapid amplification of cDNA ends; PCR, polymerase chain reaction; kb, kilobase(s); bp, base pair(s). a biotin-containing enzyme, catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. Malonyl-CoA is the C2 donor in the de novosynthesis of long chain fatty acids and in their elongation into very long chain fatty acids (1Wakil S.J. Am. J. Chem. Soc. 1958; 80: 6465Crossref Scopus (60) Google Scholar, 2Nugteren D.H. Biochim. Biophys. Acta. 1965; 106: 280-290Crossref PubMed Scopus (199) Google Scholar). Malonyl-CoA is also involved in the synthesis of polyketides (3Hopwood D.A. Sherman D.H. Annu. Rev. Genet. 1990; 24: 37-66Crossref PubMed Google Scholar), and there are indications that it may be involved in the synthesis of an as yet unknown compound or pathway (4Al-Feel W. Wakil S.J. Chirala S.S. FASEB J. 1993; 7 (abstr.): 1229Google Scholar,5Haßlacher M. Ivessa A.S. Paltauf F. Kohlwein S.D. J. Biol. Chem. 1993; 268: 10946-10952Abstract Full Text PDF PubMed Google Scholar). Moreover, malonyl-CoA is a regulator of the palmitoyl-CoA–carnitine shuttle system that is involved in the mitochondrial oxidation of long chain fatty acids (6McGarry J.D. Takabayashi Y. Foster D.W. J. Biol. Chem. 1978; 253: 8294-8300Abstract Full Text PDF PubMed Google Scholar).ACC is a complex multifunctional enzyme system. In prokaryotes, it is composed of three distinct and separable proteins: the biotin carboxyl carrier protein, the biotin carboxylase, and the transcarboxylase. In eukaryotes, however, the individual proteins of ACC are associated with a single multifunctional polypeptide (M r265,000) that is encoded by a single gene. We prefer to refer to this form of ACC as ACC1. The cDNAs coding for the yeast (7Al-Feel W. Chirala S.S. Wakil S.J. Proc. Natl. Acad. Sci. U. S. A. 1992; 89: 4534-4538Crossref PubMed Scopus (82) Google Scholar), rat (8Lopez-Casillas F. Bai D.-H. Luo X. Kong I.-S. Hermodson M.A. Kim K.-H. Proc. Natl. Acad. Sci. U. S. A. 1988; 85: 5784-5788Crossref PubMed Scopus (136) Google Scholar), chicken (9Takai T. Yokoyama C. Wada K. Tanabe T. J. Biol. Chem. 1988; 263: 2651-2657Abstract Full Text PDF PubMed Google Scholar), and human (10Abu-Elheiga L. Jayakumar A. Baldini A. Chirala S.S. Wakil S.J. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 4011-4015Crossref PubMed Scopus (157) Google Scholar) ACC1 carboxylases have been cloned and sequenced. The predicted amino acid sequences of the ACC1 carboxylases are very similar, there being a greater than 90% identity among the animal ACC1 carboxylases and about 35% similarity between the animal and yeast ACC1 carboxylases. They immunologically cross-react with each other. The ACC1 carboxylases are highly enriched in lipogenic tissues and are under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA (11Hardie D.G. Prog. Lipid Res. 1989; 28: 117-146Crossref PubMed Scopus (145) Google Scholar, 12Kim K.-H. Lopez-Casillas L.A. Bai D.H. Luo X. Pape M.E. FASEB J. 1989; 3: 2250-2256Crossref PubMed Scopus (172) Google Scholar, 13Thampy K.G. Wakil S.J. J. Biol. Chem. 1988; 263: 6447-6453Abstract Full Text PDF PubMed Google Scholar, 14Thampy K.G. Wakil S.J. J. Biol. Chem. 1988; 263: 6454-6458Abstract Full Text PDF PubMed Google Scholar, 15Mabrouk G.M. Helmy I.M. Thampy K.G. Wakil S.J. J. Biol. Chem. 1990; 265: 6330-6338Abstract Full Text PDF PubMed Google Scholar, 16Quayl K.A. Denton R.M. Brownsey R.W. Biochem. J. 1993; PubMed Scopus Google Scholar, W. Wakil S.J. J. Biol. Chem. 1993; Scholar). The levels and of the ACC1 carboxylase in lipogenic tissues in to the and of the or the of ACC1 by the of the gene ACC1 or by the phosphorylation levels of the ACC1 On the other hand, a or with the synthesis of the ACC1 carboxylase and its by of the or by with carboxylase (ACC2) from rat heart, a in which or fatty acid synthesis Proc. Soc. Biol. 1965; PubMed Scopus Google Scholar, Biochim. Biophys. Acta. PubMed Scopus Google Scholar), was in by Thampy K.G. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar) and to a The ACC2 carboxylase a of biotin as a and to phosphorylation/dephosphorylation and citrate in a to ACC1 K.G. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar). antibodies not the of ACC2, to the in a blot K.G. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar), suggesting that the two are different the and have very sequences were by the that ACC2 is also present at levels in skeletal A. L.A. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar, L.A. Biochem. J. 1990; PubMed Scopus Google Scholar). Moreover, ACC2 is also found in rat liver Brownsey W. J. Biol. Chem. Full Text PDF PubMed Google Scholar) and in human liver with rat liver ACC1 and ACC2 showed that the two isoforms not cross-react the amino acid sequences of isolated from each carboxylase a of similarity Brownsey W. J. Biol. Chem. Full Text PDF PubMed Google physiological of ACC2 is not at this the presence of ACC2 in and as the form of carboxylase to that ACC2 and its malonyl-CoA are involved in the regulation of fatty acid oxidation by tissues K.G. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar, A. L.A. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar, J. J. PubMed Scopus Google Scholar). to the of fatty acid oxidation in and with carboxylase and malonyl-CoA levels to the that fatty acid oxidation in the is to carboxylase a that is with the that ACC2 is present in and tissues for the of fatty acid oxidation L.A. T. A. J. Biol. Chem. Full Text PDF PubMed Google Scholar, S. J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar). the of ACC2 and its to ACC1, we isolated ACC2 cDNA from human liver and we the sequence of the cDNA encoding the human ACC2 carboxylase and the of its gene. We also the of ACC2 in human and mouse tissues and evidence for the presence of an isoform of ACC2 in human long been that the of ACC by are the of or as the of it is to form of ACC from animal of evidence the of at two ACC the and the 280-kDa ACC1 and ACC2 biotin as the ACC1 is immunologically distinct from ACC2 K.G. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar, A. L.A. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar, L.A. J. K. F. J. Biochem. PubMed Scopus Google Scholar). The two isoforms also different the acetyl-CoA L.A. J. K. F. J. Biochem. PubMed Scopus Google Scholar). The the the first evidence that ACC1 and ACC2 are the of two the predicted amino acid sequences of ACC1 and ACC2 showed the presence of an amino acids at the of ACC2 that may for the in and may be involved in the ACC2 a or of the of the predicted amino acid sequence of the region of ACC2 by using the J. J. Biol. PubMed Scopus Google Scholar) and of the predicted to the 1978; Google Scholar) showed that the peptide the first amino acids was in and that a of sequences was highly in The of the peptide that ACC2 may be a or The of ACC2 with and may its the this however, the physiological significance of the 280-kDa ACC2 and its isoform is not evidence a for ACC2 in the regulation of fatty acid The presence of ACC2 in tissues as and skeletal in which very fatty acid synthesis in which there are very levels of fatty acid is to the synthesis of malonyl-CoA, a of the system and to mitochondrial fatty acid its primarily from the oxidation of fatty acids and The and between the of the two to the of the of fatty acids as a and acetyl-CoA as a as the oxidation of the the mitochondrial a in the of the two of fatty acids in an in the to a in the of the complex that in a in oxidation J. J. PubMed Scopus Google Scholar, M. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar). oxidation by the of the complex for 1989; Full Text PDF PubMed Scopus Google Scholar), to an in the and a in fatty acid oxidation by the M. J. L.A. J. Biol. Chem. 1993; 268: Full Text PDF PubMed Google Scholar). be by the of from an in the of acetyl-CoA J. PubMed Scopus Google Scholar). the presence of ACC2 in and tissues and the of its malonyl-CoA in a for and ACC2 in the oxidation of fatty acids and by and In this is a of the system that long chain fatty the mitochondrial also is involved in the of acetyl-CoA from the to the the the presence of the by the acetyl-CoA from the to the it is by ACC2 into malonyl-CoA, a of J.D. M. Foster D.W. Rev. 1989; PubMed Scopus Google Foster D.W. J.D. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google and the fatty for In this ACC2 and are in the regulation of fatty acid and oxidation in the ACC2 may also be in the and by malonyl-CoA for the elongation of fatty acids into very long chain acids that are for the of the is that malonyl-CoA is for the synthesis of as yet unknown a or in a pathway that is for as ACC is for the and of yeast (4Al-Feel W. Wakil S.J. Chirala S.S. FASEB J. 1993; 7 (abstr.): 1229Google Scholar, M. Ivessa A.S. Paltauf F. Kohlwein S.D. J. Biol. Chem. 1993; 268: 10946-10952Abstract Full Text PDF PubMed Google Scholar) in the of in the of the and and of the S. K. K. Y. A. M. J. Biol. PubMed Scopus (82) Google Scholar, M. Ivessa A.S. Kohlwein S.D. Biol. PubMed Scopus Google Scholar). Acetyl-CoA carboxylase (ACC), 1The abbreviations used are: ACC, acetyl-CoA carboxylase; RACE, rapid amplification of cDNA ends; PCR, polymerase chain reaction; kb, kilobase(s); bp, base pair(s). 1The abbreviations used are: ACC, acetyl-CoA carboxylase; RACE, rapid amplification of cDNA ends; PCR, polymerase chain reaction; kb, kilobase(s); bp, base pair(s). a biotin-containing enzyme, catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. Malonyl-CoA is the C2 donor in the de novosynthesis of long chain fatty acids and in their elongation into very long chain fatty acids (1Wakil S.J. Am. J. Chem. Soc. 1958; 80: 6465Crossref Scopus (60) Google Scholar, 2Nugteren D.H. Biochim. Biophys. Acta. 1965; 106: 280-290Crossref PubMed Scopus (199) Google Scholar). Malonyl-CoA is also involved in the synthesis of polyketides (3Hopwood D.A. Sherman D.H. Annu. Rev. Genet. 1990; 24: 37-66Crossref PubMed Google Scholar), and there are indications that it may be involved in the synthesis of an as yet unknown compound or pathway (4Al-Feel W. Wakil S.J. Chirala S.S. FASEB J. 1993; 7 (abstr.): 1229Google Scholar,5Haßlacher M. Ivessa A.S. Paltauf F. Kohlwein S.D. J. Biol. Chem. 1993; 268: 10946-10952Abstract Full Text PDF PubMed Google Scholar). Moreover, malonyl-CoA is a regulator of the palmitoyl-CoA–carnitine shuttle system that is involved in the mitochondrial oxidation of long chain fatty acids (6McGarry J.D. Takabayashi Y. Foster D.W. J. Biol. Chem. 1978; 253: 8294-8300Abstract Full Text PDF PubMed Google Scholar). ACC is a complex multifunctional enzyme system. In prokaryotes, it is composed of three distinct and separable proteins: the biotin carboxyl carrier protein, the biotin carboxylase, and the transcarboxylase. In eukaryotes, however, the individual proteins of ACC are associated with a single multifunctional polypeptide (M r265,000) that is encoded by a single gene. We prefer to refer to this form of ACC as ACC1. The cDNAs coding for the yeast (7Al-Feel W. Chirala S.S. Wakil S.J. Proc. Natl. Acad. Sci. U. S. A. 1992; 89: 4534-4538Crossref PubMed Scopus (82) Google Scholar), rat (8Lopez-Casillas F. Bai D.-H. Luo X. Kong I.-S. Hermodson M.A. Kim K.-H. Proc. Natl. Acad. Sci. U. S. A. 1988; 85: 5784-5788Crossref PubMed Scopus (136) Google Scholar), chicken (9Takai T. Yokoyama C. Wada K. Tanabe T. J. Biol. Chem. 1988; 263: 2651-2657Abstract Full Text PDF PubMed Google Scholar), and human (10Abu-Elheiga L. Jayakumar A. Baldini A. Chirala S.S. Wakil S.J. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 4011-4015Crossref PubMed Scopus (157) Google Scholar) ACC1 carboxylases have been cloned and sequenced. The predicted amino acid sequences of the ACC1 carboxylases are very similar, there being a greater than 90% identity among the animal ACC1 carboxylases and about 35% similarity between the animal and yeast ACC1 carboxylases. They immunologically cross-react with each other. The ACC1 carboxylases are highly enriched in lipogenic tissues and are under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA (11Hardie D.G. Prog. Lipid Res. 1989; 28: 117-146Crossref PubMed Scopus (145) Google Scholar, 12Kim K.-H. Lopez-Casillas L.A. Bai D.H. Luo X. Pape M.E. FASEB J. 1989; 3: 2250-2256Crossref PubMed Scopus (172) Google Scholar, 13Thampy K.G. Wakil S.J. J. Biol. Chem. 1988; 263: 6447-6453Abstract Full Text PDF PubMed Google Scholar, 14Thampy K.G. Wakil S.J. J. Biol. Chem. 1988; 263: 6454-6458Abstract Full Text PDF PubMed Google Scholar, 15Mabrouk G.M. Helmy I.M. Thampy K.G. Wakil S.J. J. Biol. Chem. 1990; 265: 6330-6338Abstract Full Text PDF PubMed Google Scholar, 16Quayl K.A. Denton R.M. Brownsey R.W. Biochem. J. 1993; PubMed Scopus Google Scholar, W. Wakil S.J. J. Biol. Chem. 1993; Scholar). The levels and of the ACC1 carboxylase in lipogenic tissues in to the and of the or the of ACC1 by the of the gene ACC1 or by the phosphorylation levels of the ACC1 On the other hand, a or with the synthesis of the ACC1 carboxylase and its by of the or by with carboxylase (ACC2) from rat heart, a in which or fatty acid synthesis Proc. Soc. Biol. 1965; PubMed Scopus Google Scholar, Biochim. Biophys. Acta. PubMed Scopus Google Scholar), was in by Thampy K.G. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar) and to a The ACC2 carboxylase a of biotin as a and to phosphorylation/dephosphorylation and citrate in a to ACC1 K.G. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar). antibodies not the of ACC2, to the in a blot K.G. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar), suggesting that the two are different the and have very sequences were by the that ACC2 is also present at levels in skeletal A. L.A. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar, L.A. Biochem. J. 1990; PubMed Scopus Google Scholar). Moreover, ACC2 is also found in rat liver Brownsey W. J. Biol. Chem. Full Text PDF PubMed Google Scholar) and in human liver with rat liver ACC1 and ACC2 showed that the two isoforms not cross-react the amino acid sequences of isolated from each carboxylase a of similarity Brownsey W. J. Biol. Chem. Full Text PDF PubMed Google Scholar). The physiological of ACC2 is not at this the presence of ACC2 in and as the form of carboxylase to that ACC2 and its malonyl-CoA are involved in the regulation of fatty acid oxidation by tissues K.G. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar, A. L.A. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar, J. J. PubMed Scopus Google Scholar). to the of fatty acid oxidation in and with carboxylase and malonyl-CoA levels to the that fatty acid oxidation in the is to carboxylase a that is with the that ACC2 is present in and tissues for the of fatty acid oxidation L.A. T. A. J. Biol. Chem. Full Text PDF PubMed Google Scholar, S. J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar). the of ACC2 and its to ACC1, we isolated ACC2 cDNA from human liver and we the sequence of the cDNA encoding the human ACC2 carboxylase and the of its gene. We also the of ACC2 in human and mouse tissues and evidence for the presence of an isoform of ACC2 in human long been that the of ACC by are the of or as the of it is to form of ACC from animal of evidence the of at two ACC the and the 280-kDa ACC1 and ACC2 biotin as the ACC1 is immunologically distinct from ACC2 K.G. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar, A. L.A. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar, L.A. J. K. F. J. Biochem. PubMed Scopus Google Scholar). The two isoforms also different the acetyl-CoA L.A. J. K. F. J. Biochem. PubMed Scopus Google Scholar). The the the first evidence that ACC1 and ACC2 are the of two the predicted amino acid sequences of ACC1 and ACC2 showed the presence of an amino acids at the of ACC2 that may for the in and may be involved in the ACC2 a or of the of the predicted amino acid sequence of the region of ACC2 by using the J. J. Biol. PubMed Scopus Google Scholar) and of the predicted to the 1978; Google Scholar) showed that the peptide the first amino acids was in and that a of sequences was highly in The of the peptide that ACC2 may be a or The of ACC2 with and may its the this however, the physiological significance of the 280-kDa ACC2 and its isoform is not evidence a for ACC2 in the regulation of fatty acid The presence of ACC2 in tissues as and skeletal in which very fatty acid synthesis in which there are very levels of fatty acid is to the synthesis of malonyl-CoA, a of the system and to mitochondrial fatty acid its primarily from the oxidation of fatty acids and The and between the of the two to the of the of fatty acids as a and acetyl-CoA as a as the oxidation of the the mitochondrial a in the of the two of fatty acids in an in the to a in the of the complex that in a in oxidation J. J. PubMed Scopus Google Scholar, M. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar). oxidation by the of the complex for 1989; Full Text PDF PubMed Scopus Google Scholar), to an in the and a in fatty acid oxidation by the M. J. L.A. J. Biol. Chem. 1993; 268: Full Text PDF PubMed Google Scholar). be by the of from an in the of acetyl-CoA J. PubMed Scopus Google Scholar). the presence of ACC2 in and tissues and the of its malonyl-CoA in a for and ACC2 in the oxidation of fatty acids and by and In this is a of the system that long chain fatty the mitochondrial also is involved in the of acetyl-CoA from the to the the the presence of the by the acetyl-CoA from the to the it is by ACC2 into malonyl-CoA, a of J.D. M. Foster D.W. Rev. 1989; PubMed Scopus Google Foster D.W. J.D. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google and the fatty for In this ACC2 and are in the regulation of fatty acid and oxidation in the ACC2 may also be in the and by malonyl-CoA for the elongation of fatty acids into very long chain acids that are for the of the is that malonyl-CoA is for the synthesis of as yet unknown a or in a pathway that is for as ACC is for the and of yeast (4Al-Feel W. Wakil S.J. Chirala S.S. FASEB J. 1993; 7 (abstr.): 1229Google Scholar, M. Ivessa A.S. Paltauf F. Kohlwein S.D. J. Biol. Chem. 1993; 268: 10946-10952Abstract Full Text PDF PubMed Google Scholar) in the of in the of the and and of the S. K. K. Y. A. M. J. Biol. PubMed Scopus (82) Google Scholar, M. Ivessa A.S. Kohlwein S.D. Biol. PubMed Scopus Google Scholar). long been that the of ACC by are the of or as the of it is to form of ACC from animal of evidence the of at two ACC the and the 280-kDa ACC1 and ACC2 biotin as the ACC1 is immunologically distinct from ACC2 K.G. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar, A. L.A. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google Scholar, L.A. J. K. F. J. Biochem. PubMed Scopus Google Scholar). The two isoforms also different the acetyl-CoA L.A. J. K. F. J. Biochem. PubMed Scopus Google Scholar). The the the first evidence that ACC1 and ACC2 are the of two the predicted amino acid sequences of ACC1 and ACC2 showed the presence of an amino acids at the of ACC2 that may for the in and may be involved in the ACC2 a or of the of the predicted amino acid sequence of the region of ACC2 by using the J. J. Biol. PubMed Scopus Google Scholar) and of the predicted to the 1978; Google Scholar) showed that the peptide the first amino acids was in and that a of sequences was highly in The of the peptide that ACC2 may be a or The of ACC2 with and may its the this however, the physiological significance of the 280-kDa ACC2 and its isoform is not evidence a for ACC2 in the regulation of fatty acid The presence of ACC2 in tissues as and skeletal in which very fatty acid synthesis in which there are very levels of fatty acid is to the synthesis of malonyl-CoA, a of the system and to mitochondrial fatty acid The its primarily from the oxidation of fatty acids and The and between the of the two to the of the of fatty acids as a and acetyl-CoA as a as the oxidation of the the mitochondrial a in the of the two of fatty acids in an in the to a in the of the complex that in a in oxidation J. J. PubMed Scopus Google Scholar, M. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar). oxidation by the of the complex for 1989; Full Text PDF PubMed Scopus Google Scholar), to an in the and a in fatty acid oxidation by the M. J. L.A. J. Biol. Chem. 1993; 268: Full Text PDF PubMed Google Scholar). be by the of from an in the of acetyl-CoA J. PubMed Scopus Google Scholar). the presence of ACC2 in and tissues and the of its malonyl-CoA in a for and ACC2 in the oxidation of fatty acids and by and In this is a of the system that long chain fatty the mitochondrial also is involved in the of acetyl-CoA from the to the the the presence of the by the acetyl-CoA from the to the it is by ACC2 into malonyl-CoA, a of J.D. M. Foster D.W. Rev. 1989; PubMed Scopus Google Foster D.W. J.D. J. Biol. Chem. 1990; 265: Full Text PDF PubMed Google and the fatty for In this ACC2 and are in the regulation of fatty acid and oxidation in the ACC2 may also be in the and by malonyl-CoA for the elongation of fatty acids into very long chain acids that are for the of the is that malonyl-CoA is for the synthesis of as yet unknown a or in a pathway that is for as ACC is for the and of yeast (4Al-Feel W. Wakil S.J. Chirala S.S. FASEB J. 1993; 7 (abstr.): 1229Google Scholar, M. Ivessa A.S. Paltauf F. Kohlwein S.D. J. Biol. Chem. 1993; 268: 10946-10952Abstract Full Text PDF PubMed Google Scholar) in the of in the of the and and of the S. K. K. Y. A. M. J. Biol. PubMed Scopus (82) Google Scholar, M. Ivessa A.S. Kohlwein S.D. Biol. PubMed Scopus Google Scholar). We the at of for to the we used for the sequence We also for the