Acetyl CoA formation

The basic building block for fatty acid synthesis is acetyl-CoA, produced from glucose, fructose or amino acids (Figure 11.1). Acetyl-CoA formation from these precursors occurs within the mitochondrion and so, because fatty acid synthesis occurs in the cytosol, acetyl-CoA must be transported across the mitochondrial membrane. Trans-... 

In conclusion, the [NiS] mediated formation of thioesters from alkyl, CO, and thiol groups lends support to an acetyl-CoA formation pathway that comprises CO insertion into a Ni Me and an intramolecular S -C bond formation between nickel-bound acyl groups and thiolate ligands. These reactions are favored at square-planar nickel complexes that enable two-electron redox reactions and readily add fifth ligands. 

And cleavage then reverses condensation. Acetyl CoA formation Outside ready for ligation Now forms by carboxylation Malonyl CoA. 

PTA from M. thermophila has much lower values for its substrates than the ACK (Table 12 [236,240]), and lower values than other phosphotransacetylases [240]. Activity of M. thermophila PTA in the physiological direction of acetyl-CoA formation is 10-fold greater than in the direction of acetyl-phosphate formation [240]. Potassium and ammonium ions stimulate the activity of PTA about 7-fold, but phosphate, arsenate, and Na are inhibitory [240] phosphate probably acts as an end product inhibitor. Sodium also inhibits other phosphotransacetylases. 

Effect of Inhibition of Acetyl-CoA Formation on Ethyl Acetate Accumulation. Ethyl acetate has been shown to be formed from acetic acid and ethanol without any cofactors in S. cerevlslae suggesting an esterase mechanism of biosynthesis (V7). Other studies (18) found cell-free synthesis of ethyl acetate with ethanol and acetyl-CoA but not with acetic acid as a substrate. From the latter study it was proposed that ester formation in yeasts was primarily via alcoholysis of acyl-CoA compounds. Others have also suggested acetyl-CoA as an intermediate for ethyl acetate accumulation by S. cerevlslae (19). 

Arsenite is known to have some effect on oxidative phosphorylation. However, as can be seen [Figure 5c] the use of an uncoupler of oxidative phosphorylation (2,l(-dinitrophenol) did not affect accumulation of ethyl acetate. From this it would appear that the main inhibitory effect of arsenite on ethyl acetate accumulation by C. utllls is at the level of acetyl-CoA formation. Thus acetyl-CoA is implicated as a key precursor for synthesis of ethyl acetate supporting a model presented earlier [Figure it]. 

Acetoacetyl-CoA thiolase (EC 2.3.1.9) catalyses the reversible condensation of 2 molecules of acetyl-CoA yielding acetoacetyl-CoA and CoASH. The chemical equilibrium of the reaction strongly favours acetyl-CoA formation (K=5.0 x 10 at... 

The first of them is supplied by the enzyme RUBP-C/0 which catalyses the BC cycle reactions, the other one catalyses the reactions with the yet unknown enzyme x-carboxylase which leads to acetyl-CoA formation. Thus it is supposed that in chloroplasts of isoprenereleasing plants there are at least two compartments of light conversion of CO2 carbon that comes to the leaves from the air, from two different carboxilation systems or from one system but along two channels. In fig.l they are located in immediate vicinity. But the centres of carboxylation are separated, which is to be understood as a sign of the presence either of two different enzymes or two different carboxylizing centres of the same enzyme. 

The role of citrate as an intermediary in acetyl-CoA formation has been substantiated by isotope labeling studies with citrate [16,17,20], acetyl-CoA [17,18,20], and, more recently, aspartate [21] and elutamate [22-25]. 

GAT activity, detected when chloroplasts were ruptured but not with intact chloroplasts, was found to be exclusively stromal (Table 1) and was stabilized by precipitation with 75% saturation (NH )2S0. When assayed for acetyl CoA formation from acetylcarnitine, abundant CAT activity was detected, with negligible activity in the various controls (Figure 1). This activity corresponded to 300-400 nmol min" mg chi., v/hich is more than enough to account for... 

When plants are grown heterotrophically on [l- C]glucose, glycolysis and acetyl-CoA formation via pyruvate dehydrogenase yields [2- C]acetyl-CoA. The latter will label... 

Today several xenobiotics, either natural antibiotics (cerulenin, thiolactomycin) or active herbicides are known to interfere with acetyl-CoA formation, de novo fatty acid biosynthesis, desaturation of fatty acids, biosynthesis of long chain fatty acids and glycerolipid formation. This is summarized in Fig. 9. Certainly other new herbicides which interfere with the same or other particular parts of plant lipid biosynthesis will be developed in the future. From the study of the mode of action of these inhibitors in sensitive and tolerant species, one will not only be able to efficiently control weeds in crop plants and guarantee a better food production but also obtain a new and better understanding of the function of plant lipids and the regulation of plant lipid biosynthesis. 

Besides this stromal precursor availability, the highly labile PDC (8) has iDeen considered to play an important role in controlling the relative involvement of both pathways in acetyl-CoA formation since the individual subcomplexes are able to function either together or independently of each other (5) and since the end products acetyl-CoA and NADH strongly inhibit the PDC by feedloack control (5) (Table II, b). 

In terms of compartmentation the generation of acetyl CoA and isopen-tenyl pyrophosphate which are the precursors of the lipophilic domains of lipid molecules in plants is not finally understood. For this reason this topic is debated rather controversially in the literature (for review see ref. 1). The problem of generation and compartmentation of isopentenyl pyrophosphate will be dealt with in a separate contribution (H. Kleinig, this vol.). The point in question here is the intraplastid acetyl CoA formation for fatty acid synthesis. 

CHEMICAL REGULATION OF ACETYL-COA FORMATION AND DE NOVO FATTY ACID BIOSYNTHESIS IN PLANTS... 

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. 

Glyoxysomes isolated from sunflower cotyledons metabolized [U- C]llnoleate (1.31 nmol 5.35 MBq ixmor ) to [ C]acetyl-CoA In the presence of ATP, CoASH, and NAD (for principal composition of reaction mixtures see [6]). The percentage of radioactivity detected in acetyl-CoA varied from 44 to 67% after the acetyl-CoA formation had ceased in the reaction mixture. Neither this percentage of radioactivity... 

The anaerobic Clostridium yields energy by converting glucose to acetyl-CoA, formate, CO2, and H2. The reducing power is then used to produce butanol and acetone via acetoacetyl-CoA. The overall reaction for butanol and acetone production can be pictured as follows ... 

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