Citric Acid Cycle Intermediates in Amino Acid Metabolism

About half of the 20 amino acids found in proteins are biosynthesized from intermediates in the citric acid cycle or from pyruvate (Figure 20.12 and Figure 21.1). This includes glutamate, aspartate, and alanine, which can be formed by transamination from -ketoglutarate, oxaloacetate, and pyruvate, respectively. It also includes glutamine and asparagine, which are formed directly from glutamate and aspartate, respectively; and proline and arginine, which are formed in short pathways from glutamate. Finally, threonine, methionine, and isoleucine-are derived from aspartate, but will be dealt with separately.

The illustrations here and here show the transamination reactions interconverting -ketoglutarate, glutamate, and glutamine (see here) and oxaloacetate, aspartate, and asparagine (see here). Notice in each case that one enzyme is primarily involved in the anabolic reactions (making an amino acid) whereas a different enzyme is involved in the catabolic pathway (breaking down an amino acid).

To summarize:

> - Transamination of pyruvate yields alanine;
> - Transamination of oxaloacetate yields aspartate;
> - Transamination of aspartate yields asparagine;
> - Transamination of -ketoglutarate yields glutamate;
> - Transamination of glutamate yields glutamine

Glutamate has many fates and is discussed further in the first hyperlink below.

Aspartate has many fates, too. For example, its nitrogen is used in the biosynthesis of arginine and urea. Similar reactions are involved in purine nucleotide synthesis. The entire aspartate molecule is used in pyrimidine nucleotide biosynthesis. In plants and bacteria, aspartate is a precursor to three other amino acids (i.e., methionine,threonine, and isoleucine) via its conversion to homoserine (see here). Homoserine then leads in separate pathways to methionine and threonine. Threonine, in turn, can be converted to isoleucine. In bacteria, aspartic -semialdehyde is a precursor to lysine.

When bacteria reach a high enough cell density, N-acylhomoserine is synthesized and secreted at a low rate and it diffuses back into cells. There it binds to gene regulatory proteins, which, in turn, stimulate transcription of genes required to activate the phenomenon known as "quorum-sensing." This physiological response varies and can include luminescence, antibiotic synthesis, and conjugal gene transfer.

See also: Glutamate as a Precursor to Other Amino Acids, Transamination in Amino Acid Metabolism (from Chapter 20), De Novo Pyrimidine Nucleotide Metabolism (from Chapter 22), De Novo Biosynthesis of Purine Nucleotides (from Chapter 22), Glutaminase