Pyruvic acids, degradation

The acetyl-CoA derived from amino acid degradation is normally insufficient for fatty acid biosynthesis, and the acetyl-CoA produced by pyruvate dehydrogenase and by fatty acid oxidation cannot cross the mitochondrial membrane to participate directly in fatty acid synthesis. Instead, acetyl-CoA is linked with oxaloacetate to form citrate, which is transported from the mitochondrial matrix to the cytosol (Figure 25.1). Here it can be converted back into acetyl-CoA and oxaloacetate by ATP-citrate lyase. In this manner, mitochondrial acetyl-CoA becomes the substrate for cytosolic fatty acid synthesis. (Oxaloacetate returns to the mitochondria in the form of either pyruvate or malate, which is then reconverted to acetyl-CoA and oxaloacetate, respectively.)... 

Photolytic. Dalapon (free acid) is subject to photodegradation. When an aqueous solution (0.25 M) was irradiated with UV light at 253.7 nm at 49 °C, 70% degraded in 7 h. Pyruvic acid is formed which is subsequently decarboxylated to acetaldehyde, carbon dioxide, and small quantities of 1,1-dichloroethane (2-4%) and a water-insoluble polymer (Kenaga, 1974). The photolysis of an aqueous solution of dalapon (free acid) by UV light (X = 2537 A) yielded chloride ions, carbon dioxide, carbon monoxide, and methyl chloride at quantum yields of 0.29, 0.10, 0.02, and 0.02, respectively (Baxter and Johnston, 1968). 

Thiamine pyrophosphate is a coenzyme for several enzymes involved in carbohydrate metabolism. These enzymes either catalyze the decarboxylation of oi-keto acids or the rearrangement of the carbon skeletons of certain sugars. A particularly important example is provided by the conversion of pyruvic acid, an oi-keto acid, to acetic acid. The pyruvate dehydrogenase complex catalyzes this reaction. This is the key reaction that links the degradation of sugars to the citric acid cycle and fatty acid synthesis (chapters 16 and 18) ... 

The tricarboxylic acid cycle not only takes up acetyl CoA from fatty acid degradation, but also supplies the material for the biosynthesis of fatty acids and isoprenoids. Acetyl CoA, which is formed in the matrix space of mitochondria by pyruvate dehydrogenase (see p. 134), is not capable of passing through the inner mitochondrial membrane. The acetyl residue is therefore condensed with oxaloacetate by mitochondrial citrate synthase to form citrate. This then leaves the mitochondria by antiport with malate (right see p. 212). In the cytoplasm, it is cleaved again by ATP-dependent citrate lyase [4] into acetyl-CoA and oxaloacetate. The oxaloacetate formed is reduced by a cytoplasmic malate dehydrogenase to malate [2], which then returns to the mitochondrion via the antiport already mentioned. Alternatively, the malate can be oxidized by malic enzyme" [5], with decarboxylation, to pyruvate. The NADPH+H formed in this process is also used for fatty acid biosynthesis. 

After pyruvic acid and acetaldehyde had been identified as intermediate products of glycolysis, sugar degradation could be formulated schematically by the following equations ... 

During a fast, the liver is flooded with fatty acids mobilized from adipose tissue. The resulting elevated hepatic acetyl CoA produced primarily by fatty acid degradation inhibits pyruvate dehydrogenase (see p. 108), and activates pyruvate carboxylase (see p. 117). The oxaloacetate thus produced is used by the liver for gluconeogenesis rather than for the TCA cycle. Therefore, acetyl Co A is channeled into ketone body synthesis. 

When considering the mechanism of the malo-lactic fermentation, the possibility that malic acid may be converted first to oxaloacetic acid (by malic dehydrogenase) must be recognized. This acid could then be decarboxylated to pyruvic acid, and subsequent reaction would yield lactic acid. However, if this were the case, there then should be no situation where malic acid would be decarboxylated faster than oxaloacetic acid. This, however, was shown to occur at pH 6 (14). Similarly, Flesch and Holbach (15) report that malic dehydrogenase has an optimal pH of 10, but that the malo-lactic reaction proceeds at pH 5.6. Therefore, it would not seem likely that the cell would degrade malic acid by this mechanism hence, the oxaloacetic acid intermediate would not be available to the organism. 

Oxidation of SeC 144 derivatives also generates AAla derivatives. Hoffmann degradation of u,p-diaminopropanoic acid, 145 Bergmann s re action11461 of condensation of amides with pyruvic acid, N-hydroxylation followed by dehydration, 147 and N-chlorination/dehydro-chlorination 122-124 have also been used for the synthesis of AAla derivatives. 

The sequence of biochemical steps by which glucose is degraded to pyruvic acid is called glycolysis or the Embden-Meyerhof-Parnas (EMP) Pathway, and is shown... 

The degradation of nicotinic acid by Clostridium barkeri involves the cleavage of the intermediate 2,3-dimethylmalate 132 from which propionic and pyruvic acids are formed by a specific lyase (EC 4.1.3.32). In the reverse direction, the enzyme must have the unusual capacity to deprotonate propionic acid at the a-carbon instead of the carboxylic acid function, or next to an anionic car-boxylate. Purified dimethylmalic acid aldolase has been used to catalyze the stereospecific addition of 133 to the oxoacid acceptor, yielding the (2R,3S) configurated dimethylmalic acid 132 at the multi-gram scale [381]. The substrate tolerance of this enzyme has not yet been determined. 

Morgan and Lenz (1992) showed that the major water-soluble metabolite in wheat grain was 2-amino-3,3-dime-thyl butanoic acid (Figure 7.19). This material accounted for 11% of the total radioactive residue. Degradation of the heterocyclic ring to form the semicarbazone of pyruvic acid was reported in a potato rotational crop study by Prestel et al (1976). However, Scholz (1982) was unable to repeat this observation. 

In animals the acetyl CoA produced from fatty acid degradation cannot be converted into pyruvate or oxaloacetate. Although the two carbon atoms from acetyl CoA enter the citric acid cycle, they are both oxidized to C02 in the reactions catalyzed by isocitrate dehydrogenase and a-ketoglutarate dehydrogenase (see... 

The cycle oxidizes pyruvate (formed during the glycolytic breakdown of glucose) to C02 and H20, with the concomitant production of energy. Acetyl CoA from fatty acid breakdown and amino acid degradation products are also oxidized. In addition, the cycle has a role in producing precursors for biosynthetic pathways. 

The citric acid cycle, also known as the TCA (tricarboxylic acid) cycle or Krebs cycle (after its discoverer in 1937), is used to oxidize the pyruvate formed during the glycolytic breakdown of glucose into C02 and H20. It also oxidizes acetyl CoA arising from fatty acid degradation (Topic K2), and amino acid degradation products (Topic M2). In addition, the cycle provides precursors for many biosynthetic pathways. 

---