Amino Acids that form α-ketoglutarate via Glutamate

1. Glutamine: This amino acid is hydrolyzed to glutamate and ammonia by the enzyme glutaminase. Glutamate is converted to α-ketoglutarate by transamination or through oxidative deamination by glutamate dehydrogenase.

2. Proline: This amino acid is oxidized to glutamate. Glutamate is transaminated or oxidatively deaminated to form α-ketoglutarate.

3. Arginine: This amino acid is hydrolyzed by arginase to produce ornithine (and urea). [Note: The reaction occurs primarily in the liver as part of the urea cycle.] Ornithine is subsequently converted to α-ketoglutarate, with glutamate semialdehyde as an intermediate.

4. Histidine: This amino acid is oxidatively deaminated by histidase to urocanic acid, which subsequently forms N-formiminoglutamate  ([FIGlu], Fig. 1). FIGlu donates its formimino group to tetrahydrofolate (THF), leaving glutamate, which is degraded as described above. [Note: Individuals deficient in folic acid excrete increased amounts of FIGlu in the urine, particularly after ingestion of a large dose of histidine. The FIGlu excretion test has been used in diagnosing a deficiency of folic acid.

Figure 1: Degradation of histidine. NH₃ = ammonia.