Acetyl-CoA carboxylase ACCase

Acetyl-CoA carboxylase (ACCase) carboxylates acetyl-CoA into malo-nyl-CoA and therefore represents the first committed step in fatty acid biosynthesis. ACCase is a multimer essential for cell growth whose components are highly conserved among bacteria, making it a promising broad-spectrum target [8]. 

A Inhibition of acetyl CoA carboxylase (ACCase) Aryloxyphenoxy- propionates Cyclohexanediones oximes 1... 

Fatty acid synthesis inhibitor, by inhibition of acetyl CoA Carboxylase (ACCase)... 

The pathway from acetate to palmitic acid (actually a palmitic acid-acyl carrier protein complex) involves at least nine enzymes acetyl CoA synthetase, acetyl CoA carboxylase, and the seven enzyme fatty acid synthetase complex. We chose first to test the effect of these compounds on acetyl CoA carboxylase (ACCase) activity. There were several reasons to select ACCase as the... 

Surprises or unpredicted events can happen. The early dogma, also based largely on our experience of triazine resistance, suggested that soil residual activity of herbicides was an important, if not essential, contributor to the selection of resistant biotypes. The subsequent development of multiple instances of paraquat resistance, followed by resistance to acetyl CoA carboxylase (ACCase) inhibitors, demonstrated that soil activity was not necessary for resistance to evolve. 

Sethoxydim (e.g., Poast ) inhibits acetyl CoA carboxylase (ACCase) which is the first committed step in de novo fatty acid synthesis. SR corn was achieved by traditional breeding and selection for the herbicide insensitive ACCase allele and was introduced in 1996. SR corn accounted for less than 0.3% of corn acres in any one year and is no longer commercially available in field com (Fig. 6.1.4). 

Acetyl-CoA-carboxylase (ACCase) plays a fundamental role in fatty acid metabolism and is a biotinylated errzyme that catalyzes the carboxylation of acetyl-CoA. 

Acetyl-CoA carboxylase (ACCase) 621 Acetyl-CoA synthase I (ACSI) 528 Acinetohacter baumannii 611 actinomycetes 495 Adenylate energy charge (AEC) 651 aerobic thermophiles 521 aetheramides 472 Agrobacterium tumefaciens 607 ajudazols 466... 

The synthesis of malonyl-CoA (14) from acetyl-CoA (15), which also occurs in the stroma, with acetyl-CoA carboxylase (ACCase) is the first committed step of fatty acid biosynthesis (Fig. 2.3). Malonyl-CoA produced by plastids primarily is used for fatty acid biosynthesis (Ohlrogge et al., 1993). 

Methods for the growth of plant material and assay of acetyl-CoA carboxylase (ACCase) or propionyl-CoA carboxylase activity are given In [6]. Purification of Isoforms of maize ACCase and kinetic analysis is given in [7] and purification of Poa annua ACCase in [8]. 

Acetyl-CoA carboxylase (ACCase) catalyses the ATP-dependant carboxylation of acetyl-CoA to form malonyl-CoA, thus providing the essential substrate for fatty acid biosynthesis. Dicotyledonous plants contain two forms of ACCase a multifunctional enzyme (typel) wich is presumed to be cytosolic, and a multi-subunit complex (typell) located in the plastid wich is responsible for de novo fatty acid synthesis. In prokaryotes, the ACCase is a type II enzyme comprising biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP) and a carboxyl transferase with two subunits (CTa and CTp). The cDNA encoding the B.napus CXp and BCCP have already been cloned (Elborough et a/.,1995) as have the cDNAs encoding the BC and BCCP from tobacco and Arabidopsis respectively (Shorrosh et al, 1995 Choi et al.y 1995). 

Plant acetyl CoA carboxylase [EC 6.4.1.3] is one of the pivotal enzymes of fatty acid biosynthesis in both seed and leaf tissue and is thought to be an important regulatory step of de novo fatty acid synthesis in chloroplasts (Post Beittenmiller et al., 1992). Its central role reflects its importance as a target for commercial herbicides. Two forms of ACCase are present in dicot plants. The chloroplast is thought to be the site for de novo fatty acid synthesis in mesophyll cells and BCCP has been shown to reside within the chloroplast. It is therefore reasonable to suppose that a type II Brassica napus ACCase is mainly associated with de novo lipid synthesis. Specific herbicides differentiate between the two forms of acetyl CoA carboxylase (ACCase) found in dicotyledonous plants. 

Acetyl-CoA carboxylase (ACCase) catalyzes the ATP dependent carboxylation of acetyl-CoA to form malonyl-CoA. This reaction is the first committed step in fatty acid biosynthesis and is a potentially rate-limiting step in the process. Two forms of ACCase have been observed - a prokaryotic and a eukaryotic form. In the prokaryotic form, the biotin carboxylase, biotin carboxyl carrier protein and carboxyl transferase components of ACCase are associated with different polypeptides in a multi-subunit (MS) complex (Samols et al. 1988). In contrast, the eukaryotic form comprises multimers of a single multifunctional (MF) polypeptide of200 kDa. Dicots have been reported to have an MS plastidial ACCase and an MF extra-plastidial ACCase while grasses and other monocots are believed to have the MF ACCase in both plastids and extra-plastidial sources (Sasaki et al. 1995). 

Acetyl-CoA carboxylase (ACCase, EC 6.4.1.2) catalyzes an ATP-dependent conversion of acetyl-CoA to malonyl-CoA, which is a regulated step in de novo synthesis of fatty acids that takes place in chloroplasts. In soybean, the chloroplast ACCase is apparently a multiprotein, prokaryotic type of complex [1], that is thought to consist of 4 subunits biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and the alpha and beta transcarboxylase subunits (a- and p-CT). The study of... 

Acetyl-CoA carboxylase (ACCase) catalyzes the first committed step in the fatty acid synthesis, namely, the formation of malonyl-CoA. Two forms of the enzyme, the prokaryotic and the eukaryotic forms, have been found in plants (1-4). The prokaryotic ACCase is composed of several subunits, one of which is encoded in plastid genome and named accD, and exists in plastids. The eukaryotic ACCase is composed of a single multi-functional polypeptide and exists in cytosol. However, Gramineae do not have the prokaryotic ACCase in plastids, but have the eukaryotic ACCase because of the loss of accU gene in plastids. The eukaryotic ACCase substitutes for the prokaryotic ACCase in Gramineae. It is unknown whether plants in other families loss the prokaryotic ACCase. To answer this question, we examined the prokaryotic ACCase in 28 plant families (5). 

The water soluble vitamin, biotin, acts as a cofactor for a set of enzymes that catalyze carboxylation, decarboxylation or transcarboxylation reactions (Moss and Lane, 1971). In plants we have characterized four biotin-containing enzymes each of which catalyze reactions required in lipid metabolic processes. These enzymes are the homomeric and heteromeric isozymes of acetyl-CoA carboxylase (ACCase), methylcrotonyl-CoA carboxylase (MCCase) and geranoyl-CoA carboxylase (GCCase). The studies of these biotin-containing enzymes has led to an interest in biotin biosynthesis, and we have cloned the gene coding for biotin synthase. 

A series of 2-(4-(1,X-naphthyridinyloxy)phenoxy)propan-oic acids were prepared for evaluation as potential grass herbicides and to assess their ability to inhibit maize acetyl-CoA carboxylase (ACCase). A new regiospecific pyridine annulation procedure was employed to prepare the key 2-chloro-l,6-, 1,7-, and 1,8-naphthyridine intermediates. Of the compounds prepared, only the 6-chloro-l,5-naphthyridinyloxyphen-oxy propanoic acid displayed substantial levels of herbicidal activity. The relative levels of herbicidal activity in this series of propanoic acids could be explained by the ability of these materials to inhibit ACCase. 

At least six biotinylated polypeptides can be detected in extracts from plants (1). These polypeptides are approximately 240 kDa, 120 kDa, 75 kDa, 60 kDa, 39 kDa and 34 kDa in size. Furthermore, the biotin enzymes, acetyl-CoA carboxylase (ACCase), propionyl-CoA carboxylase (PCCase), methylcrotonyl-CoA carboxylase (MCCase), pyruvate carboxylase (1) and geranoyl-CoA carboxylase (GCCase) are detectable in extracts from plants. We have undertaken biochemical and molecular biological approaches to identify and characterize the enzymes these polypeptides represent. 

Acetyl-CoA carboxylase (ACCase) catalyzes the synthesis of malonyl-CoA, the first intermediate in fatty acid synthesis. There are two forms of ACCase a prokaryote form consisting of three protein components, biotin carboxylase, carboxyltransferase, and biotin carboxylase carrier protein, and a eukaryote form consisting of three functional domains on a single polypeptide. About 20 years ago, Kannangara and Stumpf reported the existence of the prokaryote form in spinach chloroplasts [1], the major site of fatty acid synthesis, but this finding has been dismissed because the prokaryote form has not yet been purified and the purified ACCases from various plants are all eukaryote form consisting of a subunit size of about 200 kDa, like that of the mammal enzyme. 

With ethyl-AMP and AMPI specific inhibitors of the two independent routes of acetyl-CoA formation in plastids are available. Several specific xenobiotics block efficiently de novo fatty acid biosynthesis at different steps and enzyme levels (Figure 3). Graminicides such as diclofop, sethoxydim or cycloxydim are specific inhibitors of acetyl-CoA carboxylase (ACCase) of grasses [10], the antibiotics cerulenin and thiolactomycin are inhibitors which affect certain of the li-ketoacyl-ACP synthases (KAS I, II and III). With these xenobiotics one can control the metabolite flow through the fatty acid biosynthesis pathway and obtain a better understanding of the regulation of the plants de novo fatty acid biosynthesis and the enzymes involved. 

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