Oxalacetic acid synthesis

The basic starting substrate for fatty acid synthesis is acetyl-CoA (see below). In ruminants, the provision of this substrate is straightfoward. Acetate from blood (+ CoA + ATP) is converted by the cytosolic acetyl-CoA synthase (EC 2.3.1.169) to AMP and acetyl-CoA, which can then be used for fatty acid synthesis. In non-ruminants, glucose is converted via the glycolytic pathway to pyruvate, which is, in turn, converted to acetyl-CoA in mitochondria. Acetyl-CoA thus formed is converted to citrate which passes out to the cytosol where it is cleaved by ATP-citrate lyase (EC 2.3.3.8) to acetyl-CoA + oxalacetate (OAA). This transport of acetyl-CoA from... 

Both of the N-acylated neuraminic acids mentioned have been synthesized. Comforth, Daines, and Gottschalk192 made the first synthesis of N-acetylneuraminic acid. They condensed 2-acetamido-2-deoxy-D-glucose with oxalacetic acid at pH 11, and obtained a low yield (about 2%). Carroll and Comforth193 obtained a higher yield from 2-acetamido-2-deoxy-D-mannose and oxalacetic acid. 

The essential starting material for the total synthesis of ( )-aku-ammigine (21) and (+ )-tetrahydroalstonine (22) was the tetracyclic unsaturated ketone 23 (3). This was prepared by condensation of tryp-tamine hydrochloride with oxalacetic acid monomethyl ester which gave the tetrahydro- 8-carboline 24. 

Aldol reactions of this type, involving 2-acetamido-2-deoxyaldohexoses, have been studied in connection with the chemical synthesis of A -acetyl-neuraminic acid (50) and related substances, and, for this reason, the choice of the dicarbonyl compound has thus far been limited to oxalacetic acid and its esters. Oxalacetic acid condenses readily with 2-acetamido-2-deoxyaldohexoses in aqueous solution at pH 11. Under these conditions, acetamido sugars partially epimerize, and the aldol reaction takes place for both of the 2-acetamido-2-deoxyaldohexoses present. The complexity of the reaction is further increased by the formation of asymmetric centers at carbon atoms 3 and 4 of the condensation products, namely, diacids (45) and (48), and this can result in the formation of four diastereo-isomers from each sugar. The reaction using 2-acetamido-2-deoxy-o-rnannose (47) has been the one most extensively studied. In this... 

The introduction of the a-keto acid function on the way to the ulosonic acids is a main problem of their syntheses. By analogy with the biosynthetic pathway, the aldol reaction between sugar aldehydes and a pyruvate equivalents seems to be the most simple and versatile. As it has been demonstrated by Comforth [74] in the first chemical synthesis, the reaction of arabinose and oxalacetic acid as pyruvate equivalent, followed by decarboxylation afforded KDO, albeit in low yield. This condensation has been optimized by use of Ni(II) catalyst for the decarboxylation [75], In this case, reaction of D-mannose and oxalacetic acid gave KDN (11) and its D-manno epimer 37 in 70% yield [75] (Scheme 12). 

However, the lack of stereochemical control at C-4 of newly created asymmetric center, resulting in the formation of two diastereomers, is the great disadvantage. Despite this, Comforth s methodology remains still the best choice for preparation of the selected ulosonic acids. It is a case of synthesis of nine stereoisomeric 5,7-diacetamido-3,5,7,9-tetradeoxy-2-nonulosonic acids [76]. The synthesis was performed by condensation of an appropriate 2,4-diacetamido-2,4,6-trideoxy-hexopiranoses with oxalacetic acid under basic conditions (Scheme 13), used previously in the preparation of Neu5Ac [77]. 

Another hypothesis of aromatic amino acid synthesis, based on the distribution of the label in tyrosine of yeast grown on radioactive pyruvate or acetate, is that it involves the cyclic condensation of two unsym-metric 4-carbon acids, e.g., oxalacetate. The side chain of tyrosine appears to be formed from pyruvate as an intact 3-carbon unit. 

Oxalacetate and Related Compounds. Mitchell and Houlahan have suggested several plausible intermediates that may be involved in pyrimidine biosynthesis in Neurospora. Oxalacetic acid, aminofumaric acid, and aminofumaric acid diamide (Fig. 10) stimulated the growth of mutants with partial blocks in pyrimidine synthesis. Lagerkvist et al. compared the incorporation of N -labeled aspartic acid and (8,7-carbon-labeled aspartate into the pyrimidines of regenerating rat liver. Since nitrogen-labeled aspartate was less effective than carbon-labeled aspartate as a pyrimidine precursor, the authors concluded that aspartic acid was... 

Pantothenic acid, as a constituent of coenzyme A, is involved in several of the steps of the citric acid cycle these include the synthesis of citric acid from oxalacetic acid and its salts, and the oxidation by decarboxylation of a-keto-acids. 

The finding that malonic acid was a product of pyrimidine metabolism was in contrast to the common impression that malonic acid was an unnatural metabolic poison. In addition to its well-known role as an inhibitor of succinic dehydrogenase, malonic acid was metabolized by mice (399), rats (400), and microorganisms (401, 408). Also, pig heart preparations formed this acid from oxalacetic acid (403). Recent studies implicated a CoA derivative of malonic acid as an intermediate in the synthesis of fatty acids (404, 405). 

Studies of the enzymic mechanism of the citric acid synthesis by Stern and Ochoa have directly shown that citric acid, and not aconitic acid, is the primary product. It had earlier been thought that the mechanism of citric acid synthesis might be similar to that of the reaction leading in vitro to the formation of citric acid from oxalacetic and pyruvic acid in the presence of hydrogen peroxide, where oxalocitramalic acid is an intermediate. Martins, however, found this substance to be metabolically inert in animal tissue. Stern and Ochoa found that aqueous extracts of acetone-dried pigeon liver formed citrate when acetate, oxalacetate, ATP, coenzyme A, and Mg or Mn ions were present. Thus the condensation reaction is preceded by the decarboxylation of pyruvic acid and the formation of an active form of acetate. This active acetate, as discussed below, is acetyl coenzyme A. 

After this paper was submitted for publication, we proposed a new possibility (Rous, 1971) for the translocation of the substrates required in fatty acid synthesis from the mitochondria to the cytoplasm. As for gluconeogenesis, this transport would be realized by means of 4C compounds. An oxidative decarboxylation of oxalacetate would yield direcdy malonyl-CoA. This pathway should allow a better recovery of tritium from succinate 2,3- H into tty acids than that supplied by the classical pathway. 

Dideoxyheptulosonic ester 46 has been synthesized fiom glycal 43 by way of lactone 44 and dithiane 45, and KDN has been obtained by condensation of D-mannose with oxalacetic acid under basic conditions. Siereocontrolled synthesis of polyol chains employing 2-acetylthiazole as... 

The method of synthesis described for chloropyruvic acid is essentially that reported. This procedure affords the product in excellent yields from readily available materials by a short, convenient route. Other less acceptable methods involve chlorination of pyruvic acid with sulfur dichloride or hypochlorous acid and the treatment of ethyl chloro(l-hydroxyheptyl)- or (o -hydroxybenzyl)oxalacetate 7-lactone with 50% hydrochloric acid. ... 

Biotin is a growth factor for many bacteria, protozoa, plants, and probably all higher animals. In the absence of biotin, oxalacetate decarboxylation, oxalosuccinate carboxylation, a-ketoglutarate decarboxylation, malate decarboxylation, acetoacetate synthesis, citrulline synthesis, and purine and pyrimidine syntheses, are greatly depressed or absent in cells (Mil, Tl). All of these reactions require either the removal or fixation of carbon dioxide. Together with coenzyme A, biotin participates in carboxylations such as those in fatty acid and sterol syntheses. Active C02 is thought to be a carbonic acid derivative of biotin involved in these carboxylations (L10, W10). Biotin has also been involved in... 

Deoxy-araWno-heptulosonic acid 7-phosphate (10) is a metabolic intermediate before shikimic acid in the biosynthetic pathway to aromatic amino-acids in bacteria and plants. While (10) is formed enzymically from erythrose 4-phosphate (11) and phosphoenol pyruvate, a one-step chemical synthesis from (11) and oxalacetate has now been published.36 The synthesis takes place at room temperature and neutral pH... 

These syntlieses give no indication as to the structure of aspartic acid, the constitutional formula of which is based upon Kolbe s work, that it is amino-succinic acid the only synthesis of aspartic acid which confirms this constitution appears to be that by Piutti in 1887. Sodium oxalacetic ester, prepared from oxalic ester and acetic ester in the presence of sodium ethylate —... 

Kuhn and Baschang194 used the same principle for the synthesis of N-acylated neuraminic acids by condensing the potassium salt of di-ferf-butyl oxalacetate (64) with 2-acetamido-2-deoxy-D-mannose (63) (or with 2-acetamido-4,6-0-benzylidene-2-deoxy-D-glucose), they obtained the corresponding lactone (65). This was hydrolyzed with water at 90-100° to give N-acetylneuraminic lactone (66) in a yield of 34%. 

Synthesis of N-glycoloylneuraminic acid was achieved by Faillard and Blohm.198 By the general procedure of Gault1 7 and Kuhn and Baschang,194 2-deoxy-2-glycoloylamido-D-glucose was condensed with the potassium salt of di-tert-butyl oxalacetate. The tert-butyloxy lactone obtained was converted into N-glycoloylneuraminic lactone. 

Kumagai and coworkers11131 developed an enzymatic procedure to produce d-alanine from fumarate by means of aspartase (E. C. 4.3.1.1), aspartate racemase, and D-amino acid aminotransferase (Fig. 17-12). Aspartase catalyzes conversion of fumarate into L-aspartate, which is racemized to form D-aspartate. D-Amino acid aminotransferase catalyzes transamination between D-aspartate and pyruvate to produce D-alanine and oxalacetate. This 2-oxo acid is easily decarboxylated spontaneously to form pyruvate in the presence of metals. Thus, the transamination proceeds exclusively toward the direction of D-alanine synthesis, and total conversion of fumarate into D-alanine was achieved. 

The synthesis of barbituric acid can be best accomplished from diethyl malonate and urea, with an alkaline catalyst, such as sodium ethoxide in ethanol [113]. Barbituric acid-2- C has been prepared from urea- C and diethyl malonate [114]. The 4- C and 5- C compounds have been obtained by the pyrolysis of diethyl oxalacetate-3- C, which produced an equimolar mixture of 4- and 5- C barbituric acid after a rather lengthy procedure [115]. 

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