Disease relevance of ACC1

• In the first group, as represented by acetyl CoA-carboxylase of Achromobacter, the active enzyme could be resolved in three types of functional components: (1) the biotin-carboxyl carrier protein, (2) the biotin carboxylase, and (3) the carboxyl transferase [1].

High impact information on ACC1

• Aberrant mitosis in fission yeast mutants defective in fatty acid synthetase and acetyl CoA carboxylase [2].
• We have determined the crystal structures at up to 2.5-A resolution of the CT domain of yeast ACC in complex with the herbicide haloxyfop or diclofop [3].
• The carboxyltransferase (CT) domain of ACC is the site of action of commercial herbicides, such as haloxyfop, diclofop, and sethoxydim [3].
• Shifting the acc1(ts) cells to 24 degrees C after 2 h of incubation at 37 degrees C resulted in reactivation of the ACC and elevation of the ceramides and very long-chain fatty acid syntheses with normal cell-cycle progression [4].
• A Saccharomyces cerevisiae mutant strain defective in acetyl-CoA carboxylase arrests at the G2/M phase of the cell cycle [4].

Biological context of ACC1

• Whereas ACC1 is involved in cytoplasmic fatty acid synthesis, the phenotype of hfa1Delta disruptants resembles that of mitochondrial fatty-acid synthase mutants [5].
• Disruption of one ACC1 allele in a diploid wild-type strain resulted in 50% reduction of ACC1-specific mRNA and acetyl-CoA carboxylase specific activity and a marked decrease of biotin associated with a 250-kDa protein, compared to wild-type [6].
• Correspondingly, ACC biotinylation is severely reduced though not completely absent in the two bpl1 mutants studied in this work [7].
• An aryloxyphenoxypropionate and two cyclohexanediones do not inhibit growth of haploid yeast strains containing the yeast ACC1 gene, but one cyclohexanedione inhibits growth of the gene-replacement strains at concentrations below 0.2 mM [8].
• The ACC1/FAS3 gene has been mapped to the right arm of chromosome XIV by both genetic and physical methods [9].

Anatomical context of ACC1

• We report that mutants with conditional defects in the rate-limiting enzyme of fatty acid synthesis, acetyl coenzyme A carboxylase (ACC1), display unusually multilobed vacuoles, similar to those observed in vac8 mutant cells [10].
• Herbicide sensitivity determinant of wheat plastid acetyl-CoA carboxylase is located in a 400-amino acid fragment of the carboxyltransferase domain [11].
• Yeast acetyl-CoA carboxylase is associated with the cytoplasmic surface of the endoplasmic reticulum [12].
• Morphological analysis of a conditional yeast mutant in acetyl-CoA carboxylase acc1ts/mtr7, the rate-limiting enzyme of fatty acid synthesis, suggested that the synthesis of C26 VLCFAs (very-long-chain fatty acids) is important for maintaining the structure and function of the nuclear membrane [13].

Associations of ACC1 with chemical compounds

• The 5'-untranslated region of the ACC1 gene contains a sequence reminiscent of an inositol/choline-responsive element identified in genes encoding phospholipid biosynthetic enzymes [6].
• Since lipoic acid levels of ACC1 and BPL1 mutants are essentially normal, an unknown product of mitochondrial fatty acid synthesis appears to be critically reduced in malonyl-CoA-deficient yeast cells [7].
• It is concluded that the lethality of BPL1 deletants is due to the lack of malonyl-CoA-dependent VLCFA synthesis and that the viability of distinct ACC-defective point mutants is due to their maintenance of a critical level of malonyl-CoA and, hence, VLCFA production [7].
• In addition to ACC pyruvate carboxylase and an additional biotin-containing protein of unknown function fail to be biotinylated in BPL1-defective yeast mutants [7].
• Taken together these data strongly suggest that the ACC1 gene product is the primary target for soraphen A in vivo [14].

Enzymatic interactions of ACC1

• Both Snf1/4 and the AMP-activated protein kinase phosphorylate and inactivate yeast acetyl-CoA carboxylase in vitro [15].

Regulatory relationships of ACC1

• Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo [16].

Other interactions of ACC1

• Nevertheless, HFA1 and ACC1 functions are not overlapping because mutants of the two genes have different phenotypes and do not complement each other [5].
• The overexpression of FAS1 considerably stimulated MCFA formation while that of ASC2, ACC1 and FAS2 genes was not effective [17].
• Spores harboring an ACC1 deletion derived from a diploid Saccharomyces cerevisiae strain, in which one copy of the entire ACC1 gene is replaced with a LEU2 cassette, fail to grow [8].
• In Saccharomyces cerevisiae, FAS1, FAS2, and FAS3 are the genes involved in saturated fatty acid biosynthesis [18].
• The gene is closely linked to RNA2 and is allelic to the ABP2 gene of chromosome XIV [9].

Analytical, diagnostic and therapeutic context of ACC1

• Sequence analysis and comparison of the deduced amino acid sequence to protein databases unveiled 68% similarity of a 374-amino acid peptide fragment to published C termini of chicken and rat acetyl-CoA carboxylase and almost 100% identity to the product of the FAS3 gene from yeast [6].
• Data from genetic crosses of soraphen A-resistant clones with an acc1 mutant revealed that ACC1, coding for acetyl-CoA carboxylase (E.C. 6.4.1.2), is tightly linked to soraphen A resistance [14].
• So, we performed yeast two-hybrid assays to investigate potential heterologous interaction between ETO1 and three isozymes of ACC synthases from tomato [19].
• Molecular cloning, characterization, and elicitation of acetyl-CoA carboxylase from alfalfa [20].
• cDNA fragments encoding part of wheat (Triticum aestivum) acetyl-CoA carboxylase (ACC; EC 6.4.1.2) were cloned by PCR using primers based on the alignment of several biotin-dependent carboxylases [21].

References