A — ketoglutaric acid

Glutamic acid is formed m most organisms from ammonia and a ketoglutaric acid a Ketoglutaric acid is one of the intermediates m the tricarboxylic acid cycle (also called the Krebs cycle) and arises via metabolic breakdown of food sources carbohy drates fats and proteins... 

L Glutamic acid is not an essential ammo acid It need not be present m the diet because animals can biosynthesize it from sources of a ketoglutaric acid It is however a key intermediate m the biosynthesis of other ammo acids by a process known as transamination L Alanine for example is formed from pyruvic acid by transamination from L glutamic acid... 

AMP, ADP, and ATP = adenosine mono-, di-, and triphosphate IMP = inosine 5 -monophosphate AICAR = 5 -phosphoribosyl-5-amino-4-imida2olecarboxamide DAP = diaminopimelic acid PRPP = phosphoribosyl pyrophosphate a — KGA = a-ketoglutaric acid Orn = ornithine Cit = citnilline represents the one carbon unit lost to tetrahydrofolate as serine is converted to glycine. 

Glutamic acid dehydrogenase is widely distributed in microorganisms and higher plants as a catalyst in the synthesis of L-glutamic acid from a-ketoglutaric acid and free ammonia. Transaminase is contained in a wide variety of microorganisms. 

B. a-Ketoglularic acid. The ester obtained by the foregoing procedure is mixed with 600 ml. of concentrated hydrochloric acid and left overnight. The mixture is concentrated by distillation (Note 5) until the temperature of the liquid reaches 140°. It is poured into an evaporating dish and allowed to cool. The solid mass, weighing 11(3-112 g., is then pulverized. The yield of a-ketoglutaric acid is 92-93% of the theoretical for the last step, or 75-77% based upon diethyl succinate. The light tan product, obtained as described above, is suitable for most purposes, but a purer add, m.p. 109-110° (corr.) may be obtained by recrystallization from an acetone-benzene mixture. 

Oxoglutaric acid (2-oxopentane-l,5-dioic, a-ketoglutaric acid) [328-50-7] M 146.1, m 114 , 115-117 , (pK ,( see oxaloacetic acid above). Crystd repeatedly from Me2CO/ benzene, EtOAc or ethyl propionate. 

The interesting work of Hahn and Hansel, who prepared a tetracyclic lactam by intramolecular cyclization of the condensation product of tryptamine and a-ketoglutaric acid, is referred to in Section IV, B, 2. Condensation of tryptamine with a,a -diketopimelic acid (403) led, presumably by way of the 1-substituted tetrahydro-)S-carboline (404), which could not be isolated, to a product to which the tetracyclic structure 405 was assigned. 

Fig. 25.8 (a) Normal metabolism, in which phenylalanine is converted by phenylalanine 4-mono-oxygenase to tyrosine, (b) Phenylketonuria, in which there is a transamination reaction between phenylalanine and a-ketoglutaric acid. Phenylalanine 4-mono-oxygenase is absent in about 1 in every 10000 human beings because of a recessive mutant gene. 

This is the decarboxylation of a (3-keto acid which undergoes smoothly even in the absence of an enzyme. Thus, it can be said that the mother nature utilizes an organic reaction with a low activation energy. The second step of the decarboxylation is the conversion of a-ketoglutaric acid to succinic acid (Fig. 3). This is the same type of reaction as the decarboxylation of pyruvic acid. 

As mentioned in the introductory part, stereochemical course of the conversion of isocitric acid to a-ketoglutaric acid in TCA cycle is completely enantiose-lective although the reaction does not form an asymmetric carbon in the usual metabolic path. If such type of oxidative decarboxylation can be applied to synthetic compounds, it is expected that an entirely new type of asymmetric biotransformation will be developed. 

It has also been shown (22) that a-ketoglutaric acid gives rise to oxalate, viz ... 

Another observation on oxalate formation is that other a-keto acids, such as oxalosuccinic acid (74) and a-ketoglutaric acid (106) do not seem to yield oxalate directly but indirectly (123). This appears to be due to the fact that only oxaloacetic acid can function as an acetate donor. In this connection the intervention of Coenzyme A may be considered, since it is reported to function in the acetylation of sulfanilamide and choline (73) and recently was shown to take part in the enzymatic synthesis of citric acid. This concept may be illustrated as follows ... 

Enzyme Action. XLI. A Role of a-Ketoglutaric Acid in the Carbohydrate Metabolism of Wood-Destroying Molds. Arch. Biochem. 26, 375 (1950). 

B. a-Ketoglutaric acid. A mixture of 225 g. (0.82 mole) of triethyl oxalylsuccinate, 330 ml. of 12N hydrochloric acid, and 660 ml. of water is heated under reflux for 4 hours, and the mixture is distilled to dryness under reduced pressure at a bath temperature of 60-70° (Note 4). The liquid residue, which solidifies readily on standing, is warmed with 200 ml. of nitroethane on a steam bath until it is in solution. The warm solution is filtered, the funnel is washed with 40 ml. of nitroethane, and the filtrate is stirred at 0-10° for 5 hours. a-Ketoglutaric acid is separated by filtration and dried at 90° under reduced pressure for 4 hours. It is obtained as a tan solid weight 88-99 g. (73-83%) m.p. 103-110° (Note 5). 

The color of the a-ketoglutaric acid is darker if the pot temperature goes much above 90° during the evaporation and re-crystallization. 

Triethyl oxalylsuccinate, conversion to a-ketoglutaric acid, 44, 67-68 Triethyl phosphite for ethylation of hexachlorocydopentadiene, 43, 90... 

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