Acetyl coenzyme from pyruvic acid

The characteristic feature of carbohydrate breakdown in cestodes is the production of a range of complex end-products, usually organic acids, even under aerobic conditions (Table 5.4). This contrasts with predominantly aerobic organisms, such as most free-living metazoa, where the end-product of glycolysis is almost exclusively lactic acid formed from pyruvic acid. Lactic acid is produced as a result of rapid muscular contraction carried out essentially under anaerobiosis and its production ensures a rapid expenditure of energy without the limitation due to the rate of diffusion of oxygen. The anaerobic phase is followed by an aerobic phase, where pyruvic acid is metabolised to acetyl-coenzyme A which is in turn oxidised completely to... 

The metabolic functions of pantothenic acid in human biochemistry are mediated through the synthesis of CoA. Pantothenic acid is a structural component of CoA. which is necessary for many important metabolic processes. Pantothenic acid is incorporated into CoA by a. series of five enzyme-catalyzed reactions. CoA is involved in the activation of fatty acids before oxidation, which requires ATP to form the respective fatty ocyl-CoA derivatives. Pantothenic acid aI.so participates in fatty acid oxidation in the final step, forming acetyl-CoA. Acetyl-CoA is also formed from pyruvate decarboxylation, in which CoA participates with thiamine pyrophosphate and lipoic acid, two other important coenzymes. Thiamine pyrophosphate is the actual decarboxylating coenzyme that functions with lipoic acid to form acetyidihydrolipoic acid from pyruvate decarboxylation. CoA then accepts the acetyl group from acetyidihydrolipoic acid to form acetyl-CoA. Acetyl-CoA is an acetyl donor in many processes and is the precursor in important biosyntheses (e.g.. those of fatty acids, steroids, porphyrins, and acetylcholine). 

Ethyl acetates of fatty acids, mainly ethyl caproate and caprylate, are produced by yeast during alcoholic fermentation. They are synthesized from forms of the acids activated by the coenzyme A (HS-CoA), acyl-S-CoA. Acetyl-S-CoA, from pyruvic acid, may be involved in a Claisen reaction with malonyl-S-CoA, producing a new acyl-S-CoA with two additional carbon atoms (Figure 2.9). Acetyl-S-CoA thus produces butyryl-S-CoA, then hexanyl-S-CoA, etc. Specific enzymes then catalyze the alcoholysis of acyl-S-CoA into ethyl acetates of fatty acids. At the same time, the coenzyme A is regenerated. 

At the present time the data suggest multiple points of action of the adrenocortical hormones. Of the reactions which Villee et al. (1952) suggested might be influenced by the adrenocortical hormones, the condensation of pyruvate with oxaloacetate is known to require coenzyme A, as was described earlier. However, both Lipsett and Moore s (1952) experiments showing that the production of ketone bodies from pyruvate was not influenced by adrenalectomy and the observation that the acetylation of aromatic amines was not influenced by adrenalectomy (Dumm and Ralli, 1951) appear to exclude the reactions leading to the production of acetyl-CoA from pyruvate as probable points of action of the adrenocortical hormones. Therefore, of the reactions leading to the production of citrate from pyruvate and oxaloacetate, the most likely to be influenced by the adrenocortical hormones would appear to be the final condensation of acetyl-CoA with oxaloacetate. If further work should establish a direct influence of the adrenocortical hormones on the condensation of acetyl-CoA with oxaloacetate, an additional basis for the interrelations between pantothenic acid and the functions of the cortical hormones would be established. 

Indeed both -lactylthiamine pyrophosphate (XX) and a-hydroxyethyl-thiamine pyrophosphate (XXI) have been isolated and identified as products after incubation of pyruvate with a purified carboxylase preparation " . When [2- - C]pyruvate is used, the radioactivity is found in the thiazole part of the molecule after sulfite cleavage of XXL Acetaldehyde is formed from pyruvic acid by yeast carboxylase by enzymic cleavage of intermediate XXI, Uberating thiamine pyTophosphate . XXI has also been identified as intermediate in the formation of acetyl-coenzyme A from pyruvic acid by p3u uvic oxidase . The transketolase reaction has been shown to proceed via a gly-colaldehyde-enzyme intermediate here one may expect to find dihydroxy-ethylthiamine pyrophosphate as active glycol-aldehyde . Such experiments strongly support Breslow s concept of the reaction mechanism. 

Terpenes are formed in nature via the two carbons metabolism, a process enabled by acetyl coenzyme A (CoA), which is produced from pyruvic acid. Acetyl-CoA forms mevalonic acid, which loses one carbon atom by decarboxylation to yield a C5 unit— iso-pentenyl pyrophosphate ... 

The pyruvate dehydrogenase complex (PDC) is a noncovalent assembly of three different enzymes operating in concert to catalyze successive steps in the conversion of pyruvate to acetyl-CoA. The active sites of ail three enzymes are not far removed from one another, and the product of the first enzyme is passed directly to the second enzyme and so on, without diffusion of substrates and products through the solution. The overall reaction (see A Deeper Look Reaction Mechanism of the Pyruvate Dehydrogenase Complex ) involves a total of five coenzymes thiamine pyrophosphate, coenzyme A, lipoic acid, NAD+, and FAD. 

ATP and magnesium were required for the activation of acetate. Acetylations were inhibited by mercuric chloride suggesting an SH group was involved in the reaction either on the enzyme or, like lipoic acid, as a cofactor. Experiments from Lipmann s laboratory then demonstrated that a relatively heat-stable coenzyme was needed—a coenzyme for acetylation—coenzyme A (1945). The thiol-dependence appeared to be associated with the coenzyme. There was also a strong correlation between active coenzyme preparations and the presence in them of pantothenic acid—a widely distributed molecule which was a growth factor for some microorganisms and which, by 1942-1943, had been shown to be required for the oxidation of pyruvate. 

Biotin (5) is the coenzyme of the carboxylases. Like pyridoxal phosphate, it has an amide-type bond via the carboxyl group with a lysine residue of the carboxylase. This bond is catalyzed by a specific enzyme. Using ATP, biotin reacts with hydrogen carbonate (HCOa ) to form N-carboxybiotin. From this activated form, carbon dioxide (CO2) is then transferred to other molecules, into which a carboxyl group is introduced in this way. Examples of biotindependent reactions of this type include the formation of oxaloacetic acid from pyruvate (see p. 154) and the synthesis of malonyl-CoA from acetyl-CoA (see p. 162). 

Biotin (vitamin B ) is widespread in foods and is also synthesized by intestinal bacteria. It is a coenzyme for the carboxylation of pyruvate, acetyl-coenzyme-A (CoA), propionyl CoA, and /1-methyl-crotonyl CoA and is involved in fatty acid formation and in energy release from carbohydrates. In humans deficiencies only occur in patients with an abnormal gut flora and manifests itself as exfoliative dermatitis and alopecia. 

Tire enzyme does not require lipoic acid. It seems likely that a thiamin-bound enamine is oxidized by an iron-sulfide center in the oxidoreductase to 2-acetyl-thiamin which then reacts with CoA. A free radical intermediate has been detected318 321 and the proposed sequence for oxidation of the enamine intermediate is that in Eq. 15-34 but with the Fe-S center as the electron acceptor. Like pyruvate oxidase, this enzyme transfers the acetyl group from acetylthiamin to coenzyme A. Cleavage of the resulting acetyl-CoA is used to generate ATR An indolepyruvate ferredoxin oxidoreductase has similar properties 322... 

Lewisite is the most important of the organo-arseni-cal CW agents. Exposure to lewisite is quite painful, and onset of symptoms occurs rapidly (seconds to minutes) (31) in contrast to sulfur mustard for which a latency period occurs of several hours between exposure and symptoms (32). Although it is not known to have been used as a CW agent, lewisite is still considered a potential threat due to the relative ease of production and its rapid onset of action. Moreover, substantial stockpiles of lewisite are present in the United States, Russia, and in China abandoned by the Japanese Imperial Army. This may constitute a potential hazard for public health (33). The toxicity of lewisite is inter alia caused by the high affinity for the vicinal di-thiol system present in dihydrolipoic acid, a component of the pyruvate dehydrogenase complex, as is the case for other arsenicals (34). This prevents the formation of acetyl coenzyme A from pyruvate. 

The chart overleaf shows the molecules of primary metabolism and the connections between them, and needs some explanation. It shows a simplified relationship between the key structures (emphasized in large black type). It shows their origins—from CO2 in the first instance—and picks out some important intermediates. Glucose, pyruvic acid, citric acid, acetyl coenzyme A (Acetyl Co A), and ribose are players on the centre stage of our metabolism and are built into many important molecules. 

Fig. 13 Relative changes in metabolic fluxes. Relative changes in the metabolic fluxes of B. megaterium WH323 carrying TFH encoding pYYBm9 after induction of recombinant protein production with either glucose (a) or pyruvate (b) as the sole carbon source are given. AcCoA acetyl-coenzyme A Activ activation F6P fructose 6-phosphate G6P glucose 6-phosphate MAL malate OAA oxaloacetate PEP phosphoenolpyruvate PPP pentose phosphate pathway PYR pyruvate TCA tricarboxylic acid. Data adapted from [88]...

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