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

Metabolism of Nitrogenous Compounds
Incorporation of NH3 into Amino Acids and Proteins

Until 1940, Amino Acids were generally viewed as relatively inert building blocks supplied to the Organism via diet. These notions were quickly abandoned following the pioneering metabolic studies by Schoenheimer using ¹⁵NH₃ and amino acids labeled with the ¹⁵N isotope. It immediately became apparent that nitrogen is frequently transferred rapidly from one carbon Skeleton to another. These findings corroborated the hypotheses advanced earlier by Braunstein (Ch. 8, Sec. D). Braunstein pointed out that the C₄ and C₅ amino acids, aspartate and glutamate, which are closely linked to The Tricarboxylic Acid Cycle, are capable of rapidly exchanging their amino groups with those of Other Amino Acids via Transamination [Eq. (14-12), steps b and c]. Since ammonia is readily incorporated into glutamate in this process [Eq. (14-12), step a; see the following section], it is easy to conceptualize a general pathway for Amino acid synthesis.

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It soon became clear that glutamine and asparagine should be regarded as soluble, nontoxic carriers of surplus ammonia sequestered in their amide groups. Glutamate and ammonia combine under the action of an active synthetase to form glutamine [Eq. (14-12), step d], whereas another enzyme catalyzes The transfer of the amide nitrogen to aspartate to yield asparagine [Eq. (14-12), step e]. The amide nitrogen of glutamine is utilized in numerous biochemical processes, including The formation of carbamoyl phosphate [Eq. (14-12), step f; Sec. B, 2], glucosamine [Eq. (12-4)], NAD⁺ (Sec. I), Purines (Sec. L, 3), CTP (Sec. L, 1), p-aminobenzoate (Sec. J, 3), and Histidine (Sec. K).

Glutamate, glutamine, and aspartate play a pivotal role in the removal of nitrogen from Organic compounds [17]. Being a reversible reaction, transamination typically serves as the initial step in the Catabolism of excess amino acids. The addition of nitrogen to α-ketoglutarate yields excess glutamate, which is deaminated to form ammonia and subsequently glutamine. Glutamine can also donate its nitrogen for the formation of aspartate. In animal Tissues, both aspartate and glutamine (via carbamoyl phosphate) serve as precursors of urea, the principal nitrogenous excretory product. All of these interrelationships are summarized in Equation (14-12), with further details to be provided in subsequent sections.

Although the formation of glutamate via reductive amination represents the primary pathway for the incorporation of nitrogen into amino groups, the existence of alternative pathways remains entirely plausible. For instance, it has been suggested that in plants, the direct amination of Pyruvate and other α-oxo acids occurs through reactions analogous to the one catalyzed by Glutamate dehydrogenase [17a]. A bacterial enzyme is also known that catalyzes the reversible addition of ammonia to fumarate to yield aspartate (Ch. 7, Sec. F, 6, d).