Pyruvic acid biochemical oxidation

The oxidative deamination of amines to ketones, via oxaziridines, was reported as a model for the process found in oxidative deamination of a-amino-acids to pyruvic acids in biochemical systems." The primary amine, such as (58) or (59) with pyridine-2-carboxaldehyde, was converted into the imine (60) which was oxidized with m-chloroperbenzoic acid to the oxaziridine (61). Ring opening of (61) was effected with KOH in MeOH or in DMF (Scheme 8). Acetone was added to trap regenerated pyridine-2-carboxaldehyde. When other bases were used a competing reaction resulting in (62) occurred. 

Gibson, G. E., et ak, 1975. Decreased synthesis of acetylcholine accompanying impaired oxidation of pyruvic acid in rat brain minces. Biochem J. 148, 17-23. 

Glycolysis, an anaerobic process, oxidizes glucose to yield a 3-carbon compound, pyruvic acid. Obviously, a large part of the chemical energy stored in the glucose molecule remains unavailable for cellular metabolism. Fortunately, there exists a biochemical device capable of oxidizing pyruvic acid to CO2 and water in the presence of oxygen. It is known as the Krebs cycle, the tricarboxylic acid cycle, or the citric acid cycle [69-73] (see Fig. 1-13). 

The decarboxylation of pyruvic acid is an example of a more general type of biochemical reaction the decarboxylation of a-keto acids. The reaction is complex and occurs in several consecutive steps. The intermediates have been identified, but little is known of the enzymes involved. The reaction starts with the complexion of pyruvic acid with one molecule of enzyme-bound thiamine pyrophosphate. This is followed by decarboxylation of pyruvic acid and the formation of an intermediate, 2-acetylthiamine pyrophosphate, in which the aldehyde carbon of the acetyl is bound to the carbon 2 of the thiozole ring of the thiamine pyrophosphate. In the second step, the aldehyde is oxidized, the disulfide bond of enzyme-bound lipoic acid is reduced, and the free enzyme-bound thiamine pyrophosphate is restored. The tWrd step of the reaction involves the transacylation from reduced lipoic acid to CoA. Finally, lipoic acid is reoxidized by the catalytic activity of an NAD-dependent flavoprotein, lipoic dehydrogenase (see Fig. 1-14). 

Despite the biochemical importance of vitamin Bi, which appears to be concerned with most of the oxidative decarboxylations of the body, and the fact that in vitamin Bi deficiency pyruvic acid accumulates in the tissues, forming what Peters calls a biochemical lesion, there is surprisingly little histological change in deficient animals. Nevertheless, changes in some tissues have been described. 

The imravelling of the sequence of chemical steps involved in the formation and oxidation of pyruvic acid has followed from studies of the chemical activities of plant extracts and of the individual enzymes isolated from such extracts. Such studies have now yielded a very detailed picture of the biochemical reactions involved in respiration have provided us with the essential biochemical foundation for a critical study of the process of respiration as it proceeds in the living cell. In this volume where our emphasis is on the metabolism of living cells a detailed consideration of the biochemistry of respiration or of any of the other vital aspects of metabolism would be inappropriate. Nevertheless, and just in so far as interpretation of cellular metabolism requires appreciation of the nature of the underlying chemical events we can properly draw upon the findings of biochemistry. 

Senior, A.E. Shenatt, H.S.A. (1968). Biochemical effects of the hypoglycaemic compound pent-4-enoic acid and related non-hypoglycemic fatty acids. Oxidative phosphorylation and mitochondrial oxidation of pyruvate, 3-hydroxybutyrate and tricarboxylic acid-cycle intermediates. Biochem. J. 110,499-509. 

Mitochondria are also described as being the cell s biochemical powerhouse, since—through oxidative phosphorylation (see p. 112)—they produce the majority of cellular ATP. Pyruvate dehydrogenase (PDH), the tricarboxylic acid cycle, p-oxidation of fatty acids, and parts of the urea cycle are located in the matrix. The respiratory chain, ATP synthesis, and enzymes involved in heme biosynthesis (see p. 192) are associated with the inner membrane. 

PN Lowe, JA Hodgson, RN Perham. Dual role of single multi enzyme complex in the oxidative decarboxylation of pyruvate and branched-chain 2-oxo acids in Bacillus subtilis. Biochem J 215 133-140, 1983. 

As for chloroplast membranes, various compounds in mitochondrial membranes accept and donate electrons. These electrons originate from biochemical cycles in the cytosol as well as in the mitochondrial matrix (see Fig. 1-9) —most come from the tricarboxylic acid (Krebs) cycle, which leads to the oxidation of pyruvate and the reduction of NAD+ within mitochondria. Certain principal components for mitochondrial electron transfer and their midpoint redox potentials are indicated in Figure 6-8, in which the spontaneous electron flow to higher redox potentials is toward the bottom of the figure. As for photosynthetic electron flow, only a few types of compounds are involved in electron transfer in mitochondria—namely, pyridine nucleotides, flavoproteins, quinones, cytochromes, and the water-oxygen couple (plus some iron-plus-sulfur-containing centers or clusters). 

ATP plays a central role in cellular maintenance both as a chemical for biosynthesis of macromolecules and as the major soirrce of energy for all cellular metabolism. ATP is utilized in numerous biochemical reactions including the eitric acid cycle, fatty acid oxidation, gluconeogenesis, glycolysis, and pyruvate dehydrogenase. ATP also drives ion transporters sueh as Ca -ATPase in the endoplasmic reticulum and plasma membranes, H+-ATPase in the lysosomal membrane, and Na+/K+-ATPase in the plasma membrane. Chemieal energy (30.5 kJ/mol) is released by the hydrolysis of ATP to adenosine diphosphate (ADP). 

The second metabolic pathway which we have chosen to describe is the tricarboxylic acid cycle, often referred to as the Krebs cycle. This represents the biochemical hub of intermediary metabolism, not only in the oxidative catabolism of carbohydrates, lipids, and amino acids in aerobic eukaryotes and prokaryotes, but also as a source of numerous biosynthetic precursors. Pyruvate, formed in the cytosol by glycolysis, is transported into the matrix of the mitochondria where it is converted to acetyl CoA by the multi-enzyme complex, pyruvate dehydrogenase. Acetyl CoA is also produced by the mitochondrial S-oxidation of fatty acids and by the oxidative metabolism of a number of amino acids. The first reaction of the cycle (Figure 5.12) involves the condensation of acetyl Co and oxaloacetate to form citrate (1), a Claisen ester condensation. Citrate is then converted to the more easily oxidised secondary alcohol, isocitrate (2), by the iron-sulfur centre of the enzyme aconitase (described in Chapter 13). This reaction involves successive dehydration of citrate, producing enzyme-bound cis-aconitate, followed by rehydration, to give isocitrate. In this reaction, the enzyme distinguishes between the two external carboxyl groups... 

Fig. 3-10 The biochemical pathway of the tricarboxylic acid cycle (TCA cycle). Pyruvate, generated from glycolysis (Fig. 3-8), enters the cycle as acetyl-CoA (acetyl-coenzyme A), and is then degraded through a series of reactions to a 4-carbon compound, oxaloacetate. The energy resulting from the reactions is stored as ATP, which is produced through electron transport and oxidative phosphorylation (see Fig. 3-11).

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