The pathways by which amino acids are catabolized are conveniently organized according to which one (or more) of the seven intermediates listed above is produced from a particular amino acid.
A. Amino acids that form oxaloacetate
Asparagine is hydrolyzed by asparaginase, liberating ammonia and aspartate (Fig. 20.3). Aspartate loses its amino group by transamination to form oxaloacetate (see Fig. 20.3). [Note: Some rapidly dividing leukemic cells are unable to synthesize sufficient asparagine to support their growth. This makes asparagine an essential amino acid for these cells, which, therefore, require asparagine from the blood. Asparaginase, which hydrolyzes asparagine to aspartate, can be administered systemically to treat leukemia. Asparaginase lowers the level of asparagine in the plasma, thereby depriving cancer cells of a required nutrient.]
B. Amino acids that form α-ketoglutarate via glutamate 1.
Glutamine: This amino acid is hydrolyzed to glutamate and ammonia by the enzyme glutaminase (see p. 256). Glutamate is converted to αketoglutarate by transamination or through oxidative deamination by glutamate dehydrogenase (see p. 252).
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 (see p. 255).] 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. 20.4). 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. See p. 267 for a discussion of folic acid, THF, and one-carbon metabolism.]
C. Amino acids that form pyruvate 1.
Alanine: This amino acid loses its amino group by transamination to 2.
Serine: This amino acid can be converted to glycine as THF becomes N5,N10-methylenetetrahydrofolate (N5,N10-MTHF), as shown in Figure 20.6A. Serine can also be converted to pyruvate (see Fig. 20.6B).
3.
Glycine: This amino acid can be converted to serine by the reversible addition of a methylene group from N5,N10-MTHF (see Fig. 20.6A) or oxidized to CO2 and ammonia by the glycine cleavage system. [Note: Glycine can be deaminated to glyoxylate (by a d-amino acid oxidase; see form pyruvate (Fig. 20.5). [Note: Tryptophan catabolism produces alanine and, therefore, pyruvate (see Fig. 20.10 on p. 265).] p. 253), which can be oxidized to oxalate or transaminated to glycine. Deficiency of the transaminase in liver peroxisomes causes overproduction of oxalate, the formation of oxalate stones, and kidney damage (primary oxaluria type 1).] 4.