Pyruvate reactions

T. Ando and H. Miyata, Pyruvate as a fluorescence quencher Anew specttoscopic assay for pyruvate reactions, Anal. Biochem. 129, 170-175 (1983). 

Formation of pyruvate. The conversion of glucose to pyruvate requires ten enzymes (Fig. 17-7), and the sequence can be divided into four stages preparation for chain cleavage (reactions 1-3), cleavage and equilibration of triose phosphates (reactions 4 and 5), oxidative generation of ATP (reactions 6 and 7), and conversion of 3-phosphoglycerate to pyruvate (reactions 8-10). 

Some catabolic reactions of amino acid carbon chains are easy transformations to and from TCA cycle intermediates—for example, the transamination of alanine to pyruvate. Reactions involving 1-carbon units, branched-chain, and aromatic amino acids are more complicated. This chapter starts with 1-carbon metabolism and then considers the catabolic and biosynthetic reactions of a few of the longer side chains. Amino acid metabolic pathways can present a bewildering amount of material to memorize. Perhaps fortunately, most of the more complicated pathways lie beyond the scope of an introductory course or a review such as this. Instead of a detailed listing of pathways, this chapter concentrates on general principles of amino acid metabolism, especially those that occur in more than one pathway. 

Reaction (30) is favored as written for the formation of phosphoenolpyruvate by utilization of the energy of two phosphoanhydride bonds to phosphorylate pyruvate. Reaction (31) is energetically unfavored as written and would lead to the decomposition of phosphoenolpyruvate. This may be its function in some cells or under certain conditions (95). However, in the presence of inorganic pyrophosphatase to catalyze the hydrolysis of pyrophosphate, reaction (31) can also produce phosphoenolpyruvate. 

Alanine can be made by several metabolic processes. Most commonly it is made by transfer of an amine group to pyruvate (reaction 2 below). Alanine is also a product of tryptophan catabolism. 

Optical yields are lower than the corresponding reaction for methyl pyruvate. As with methyl pyruvate, a lower reaction temperature results in a higher optical yield albeit at a lower reaction rate. The influence of solvent is much more pronounced than with methyl pyruvate showing that modification in a solvent (CH2CI9) which does not interact with the catalyst is of benefit. The reaction rate of 5,200 is very fast, but gives a poor optical yield which is at odds with the methyl pyruvate reaction model. Chiral hydrogenation has also been achieved with Ph.CO.CO.Ph [26]. 

Table 5.9. A comparison of enantioselective hydrogenation of isophorone (reaction 1) on Pd and ethyl pyruvate (reaction 2) on Pt catalysts modified with DHVin isomers and DHCnd (according to Tungler, Sheldon...

For the mechanism of this reaction, see Robinson and Robinson,1918, H3i 639 1924, 145, 827.) The reaction is of wide application for example, the use of methyl-phenyl-hydrazine, CsH5(CHj)> -iN H, in the above reaction gives i-methyl-2-phenylindole, whereas pyruvic acid, CH CO COOH, when converted to its phenylhydrazone and then indolised, gives indole-2-carboxylic... 

This is an example of the Doebner synthesis of quinoline-4-carboxylic acids (cinchoninic acids) the reaction consists in the condensation of an aromatic amine with pyruvic acid and an aldehj de. The mechanism is probably similar to that given for the Doebner-Miller sj nthesis of quinaldiiie (Section V,2), involving the intermediate formation of a dihydroquinoline derivative, which is subsequently dehydrogenated by the Schiff s base derived from the aromatic amine and aldehyde. 

If the atophan does not crystallise—this is rarely the case unless pyruvic acid which has been standing for some time is employed—pour the reaction mixture into a solution of 2a g. of potassium hydroxide in 1 litre of water, and extract the resulting solution two or three times with ether. Place the ether extracts in the ETHER RESIDUES bottle. Treat the aqueous layer with 70 ml. of glacial acetic acid with vigorous stirring. Allow to stand for several hours and collect the crude atophan by filtration with suction. 

The key step in the total synthesis of rhizobitoxine is the Pd-catalyzed exchange reaction of the methyl alkenyl ether moiety in 4 with the functionalized alcohol, although the yield is low[3]. The enol pyruvate 6 (a-ethoxyacrylic acid) is prepared by the reaction of methyl a-methoxyacrylate or a-methoxy-acrylic acid (5) with ethanol catalyzed by PdCl2(PhCN)2 at room temperature in the presence of CuCli and NaH2P04[4],... 

By protodetritiation of the thiazolium salt (152) and of 2 tritiothiamine (153) Kemp and O Brien (432) measured a kinetic isotope effect, of 2.7 for (152). They evaluated the rate of protonation of the corresponding yiides and found that the enzyme-mediated reaction of thiamine with pyruvate is at least 10 times faster than the maximum rate possible with 152. The scale of this rate ratio establishes the presence within the enzyme of a higher concentration of thiamine ylide than can be realized in water. Thus a major role of the enzyme might be to change the relative thermodynamic stabilities of thiamine and its ylide (432). 

In most biochemical reactions the pH of the medium is close to 7 At this pH car boxylic acids are nearly completely converted to their conjugate bases Thus it is common practice m biological chemistry to specify the derived carboxylate anion rather than the carboxylic acid itself For example we say that glycolysis leads to lactate by way of pyruvate... 

The form in which acetate is used in most of its important biochemical reactions is acetyl coenzyme A (Figure 26 la) Acetyl coenzyme A is a thwester (Section 20 13) Its for matron from pyruvate involves several steps and is summarized m the overall equation... 

The reaction of hydroxylamine with an a,/3-unsaturated pyruvic acid (533) produced (534) (76TL1825). Hydroxylamines reacted with the nonconjugated ketoalkene (535) to produce (536) (73T2683). 

The scope of this reaction was investigated by Djerassi, °° who showed that 4-bromo ketones in the series and 2-bromo ketones in the 5a series give unsaturated 2,4-dinitrophenylhydrazones in 80-90% yield on warming under nitrogen with 1.1 moles of 2,4-dinitrophenylhydrazine in acetic acid. Cleavage with pyruvic acid affords the pure unsaturated ketones in 60-70 % yield. 

Pyridine base eliminations of a-bromo ketones cannot be recommended for general use because of the side reactions already discussed. The semi-carbazone-pyruvic acid method should be employed if strict absence of isomerization is required in the dehydrobromination of 2- or 4-bromo-3-ke-tones. This procedure is not applicable for the preparation of -3-ketones,... 

W-(Methoxycarbonyl)triphenylphosphine imide reacts with methyl trifluoro-pyruvate to form methyl A -methoxycarbonyl 2 immo-3,3,3 trifluoropropionate m 95% yield This convenient building block easily adds nucleophiles such as Gngnard reagents without competing side reactions at the ester group to form trifluoromethylated amino acids [J.S] (equation 31)... 

Reaction.—Dissolve a diop of phenylhydrazine in two diojis of glacial acetic acid, dilute with about i c.c. of water, and acid a diop of pyruvic acid. A yellow crystalline piecipitate of tlio phen)Ihydrazone, CH3.C (N.NH.C(,H5).CO.OH, is formed. 

In this scheme the reversible conversion of A to O is the reaction whose rate is to be studied, whereas the reduction of O to R is the electrode process. Scheme XIV can also represent a pseudo-first-order formation of O. A specific example is the acid-base equilibrium of pyruvic acid, shown in Scheme XV. 

FIGURE 3.13 Phosphoenolpyruvate (PEP) is produced by the euolase reaction (hi glycolysis see Chapter 19) and hi turn drives the phosphorylation of ADP to form ATP in the pyruvate kinase reaction. 

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