Biochemistry - The Chemical Reactions of Living Cells Volume 3 - D. Metzler 1980

Metabolism of Nitrogen-Containing Compounds
Synthesis and Catabolism of Compounds Belonging to the Glutamic Acid Family
Catabolism of Glutamate and Related Amino Acids

The reversibility of the Glutamate dehydrogenase reaction means that excess glutamate can easily be converted back into a-ketoglutarate. Ketoglutarate can be degraded to succinyl-CoA and subsequently, via ß-Oxidation, to malate, Pyruvate, and acetyl-CoA. The latter can re-enter The Tricarboxylic Acid Cycle and be oxidized to CO₂:

Class="center">

Many Other Amino Acids are degraded in a remarkably similar manner. In most cases, this involves Transamination to the corresponding a-keto acid, followed by ß-oxidation and Cleavage into compounds such as pyruvate and acetyl-CoA.

a. Catabolism initiated by decarboxylation

Another pathway for glutamate degradation also exists: the a-aminobutyrate shunt, discussed in Chapter 9 (Fig. 9-4). The a-aminobutyrate shunt begins not with deamination or transamination, but with a Pyridoxal phosphate-dependent decarboxylation. Since Decarboxylases are known for Most amino acids, multiple pathways usually exist for cleavage initiated in this manner. In Brain tissue, y-aminobutyrate is believed to function as an important neurotransmitter (Chapter 16, Section B, 4, b).

b. Fermentation of glutamate

Anaerobic Bacteria that utilize amino acids encounter unique challenges. Balanced fermentation reactions are required to meet their energy demands. Two Examples of glutamate fermentation are presented in Fig. 14-5. In the first of these [equation (14-23)] [43], glutamate^- is degraded to CO₂, ammonia, acetate^-, and butyrate^-:

This sequence begins with the Reactions of the y-aminobutyrate shunt (Fig. 14-5, steps a and b), after which succinic semialdehyde is reduced to y-hydroxybutyric acid utilizing NADH generated during trans-deamination. Via a CoA transferase (step d), two molecules of the acyl-CoA derivative of this hydroxy acid are formed at the expense of two acyl-CoA molecules. Next, a β,y-elimination of a Water molecule occurs, analogous to The formation of vaccenic acid [equation (12-14)]. Isomerization (catalyzified, perhaps, by the same enzyme that catalyzes the elimination) yields crotonyl-CoA (step e). The latter undergoes dismutation, whereby half of the molecules are reduced to butyryl-CoA, while the other half are hydrated and oxidized to acetoacetyl-CoA via the standard ß-oxidation pathway. Acetoacetyl-CoA is cleaved with the regeneration of two molecules of acetyl-CoA. The cleavage of butyryl-CoA yields one molecule of ATP for the Organism. A second molecule can likely be generated via Oxidative Phosphorylation in the span between the NADH generated during acetoacetyl-CoA formation and the reduction of crotonyl-CoA to butyryl-CoA. Both processes operate at redox potentials sufficiently distinct to make such coupling feasible.

FIG. 14-5. Two glutamate fermentation pathways. A. In Clostridium aminobutylicum. B. In Clostridium tetanomorphum.

The second pathway of glutamate fermentation begins with the isomerization of glutamate to ß-methylaspartate, a reaction catalyzed by a Vitamin B12-containing mutase (Table 8-6). The resulting molecular rearrangement enables an a,ß-elimination of ammonia—a process impossible for native glutamate. Hydration of the resulting unsaturated product to citramalate and the subsequent aldol Cleavage of the latter yield acetate and pyruvate. Acetate is one of the typical End products of this type of fermentation. Pyruvate can be cleaved into H₂, CO₂, and acetyl-CoA by the pyruvate-formate-lyase system, and the cleavage of acetyl-CoA can drive ATP production. Alternatively, two acetyl-CoA molecules can be converted into butyryl-CoA through Condensation and reduction. In this reaction, the reduction equivalents generated during pyruvate breakdown must be channeled into the reduction of crotonyl-CoA rather than the release of H₂. Thus, the stoichiometry remains identical to that of the fermentation processes occurring in Clostridium aminobutylicum.

c. Degradation of Proline

One pathway of proline catabolism essentially reverses its Biosynthesis from glutamate. Proline oxidase catalyzes the formation of ∆¹-pyroline-5-carboxylate.

The corresponding open-chain aldehyde formed via Hydrolysis is subsequently oxidized back into glutamate. Another degradation pathway exists, beginning with oxidation on the opposite side of the ring nitrogen to yield ∆¹-pyroline-2-carboxylate. The metabolic fate of this compound remains unclear.

Anaerobic bacteria are capable of reducing proline to 5-aminovalerate [equation (8-34)], coupling this reaction to the oxidative breakdown of another amino acid (the Stickland reaction).

The corresponding degradation pathway for 4-hydroxy-L-proline, a constituent of Collagen, yields glyoxylate and pyruvate [equation (14-24)].

In certain pseudomonads, hydroxyproline is oxidized on the opposite side of the ring nitrogen, followed by the subsequent formation of a-ketoglutarate.

d. Arginine catabolism

Arginine likewise undergoes conversion back into glutamate and a-ketoglutarate. The initial step involves the removal of the guanidinium group to yield Ornithine. This can be accomplished by arginase activity, producing urea (Fig. 14-4). Another pathway, the arginine dihydrolase pathway, is initiated by a specific hydrolase that cleaves arginine into citrulline and ammonia. Subsequent phosphorolysis of citrulline yields carbamoyl phosphate. The cleavage of the latter into CO₂ and ammonia [catalyzed by carbamate kinase; equation (14-16)] can be utilized for ATP Synthesis in microorganisms that depend on arginine.

The cleavage of L-arginine in Streptomyces griseus begins with a reaction catalyzed by a hydroxylase that performs The oxidative decarboxylation of The amino acid and its conversion into an amide [equation (14-25)].

Эта реакция в точности аналогична той, которая катализируется лизиноксигеназой [уравнение (10-49)]. В случае аргинина продуктом реакции является у-гуанидинбутирамид. Дальнейший его распад происходит путем гидролиза амидной группы и отщепления гуанидиниевой группы с образованием мочевины и у-аминобутирата. В клетках Pseudomonas putida расщепление аргинина начинается дезаминированием в соответствующую а-кетокислоту с последующим окислительным декарбоксилированием, которое осуществляет тиаминдифосфатзависимый фермент; продуктом реакции является у-гуанидинобутиральдегид. Дегидрирование и Гидролиз и в этом случае приводят к образованию у-аминобутирата [44].