Pyruvic acids, degradation oxidation

The acetyl CoA that gets on the ferris wheel can be continually replenished through glucose breakdown, or, mainly, through fatty acid degradation (oxidation), or by transformation of certain amino acids. What, however, produces the seats of the ferris wheel, or replenishes them when necessary The seats cannot be replaced by acetyl CoA, which is merely a passenger. The chemicals of the ferris wheel can be restored in part by certain amino acids that can convert to Krebs cycle intermediates. There also is an important side step in which pyruvate can be directly convert to oxaloacetate (D-8). 

Functions.— Peters, Elinnersley and their colleagues have shown that thiamine pyrophosphate acts as a co-enzjnne in carbohydrate metabolism in nervous and other tissues, and is necessary for the degradation of pyruvic acid, the oxidation derivative of lactic acid. In the absence of the vitamin, pyruvic acid accumulates, and induces the characteristic signs of avitaminosis B. ... 

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.)... 

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. 

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. 

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. 

Oxidative degradation of substituted pyruvic acids is accomplished by treating an aqueous solution of the sodium salt with 30% hydrogen peroxide (Superoxol) at 0-15°. Good descriptions have been published for the preparations of o-hydroxyphenylacetic acid (34%), 3,4-dim.ethoxy-phenylacetic acid (60%), m-chlorophenylacetic acid (57%), and o-nitro-phenylacetic acid. ... 

We now turn to the fates of the carbon skeletons of amino acids after the removal of the a-amino group. The strategy of amino acid degradation is to transform the carbon skeletons into major metabolic intermediates that can be converted into glucose or oxidized by the citric acid cycle. The conversion pathways range from extremely simple to quite complex. The carbon skeletons of the diverse set of 20 fundamental amino acids are furmeled into only seven molecules pyruvate, acetyl CoA, acetoacetyl CoA, a-ketoglutarate, succinyl CoA, fumarate, and oxaloacetate. We see here a striking example of the remarkable economy of metabolic conversions, as well as an illustration of the importance of certain metabolites. 

TCA cycle. (tricarboxylic acid cycle Krebs cycle citric acid cycle). A series of enzymatic reactions occurring in living cells of aerobic organisms, the net result of which is the conversion of pyruvic acid, formed by anaerobic metabolism of carbohydrates, into carbon dioxide and water. The metabolic intermediates are degraded by a combination of decarboxylation and dehydrogenation. It is the major terminal pathway of oxidation in animal, bacterial, and plant cells. Recent research indicates that the TCA cycle may have predated life on earth and may have provided the pathway for formation of amino acids. 

Such anaerobic metabolism can sustain life in animal cells only for short periods. However, if there is free access of oxygen, pyruvic acid passes from the above Meyerhof sequence to the tricarboxylic acid cycle (see Section 4.5), where it is completely oxidized to carbon dioxide and water. Alternative pathways exists for degrading glucose, through pentose phosphate in vertebrates, the choice of reactions varying with different tissues (see under bacteria below). All of the cell s ribose, so important in the synthesis of nucleic acids, comes from the pentose type of glycolysis. 

The most important pathways for the synthesis of acetyl-CoA (Thble) are 1) oxidative decarboxylation of pyruvate, 2) degradation of fatty acids and 3) degradation of certain amino acids. Formation of ace-tyl-CoA involves either 1) transfer of an acetyl resi-... 

Sequential degradation of the extracellular polysaccharide from R. meliloti has shown that it is composed of the octasaccharide repeating-unit (27). ° Thus, after removal of pyruvic acid residues from the methylated polysaccharide, the four p-D-glucopyranosyl residues in the side-chain were removed by oxidation, P-elimination, and, where necessary, hydrolysis with acid (see Vol. 10, p. 18). The sequence of hexopyranosyl residues in the main chain of the polysaccharide was determined by a modified Smith degradation in which the polyalcohol was methylated prior to hydrolysis with acid. 

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