Biochemistry of Amino Acids - A. Meister 1961

Intermediary Metabolism of Amino Acids
Threonine
Metabolism of Threonine

The pathways of threonine degradation have been studied in animals and microorganisms. In rats, threonine breakdown appears to be irreversible; threonine does not participate in the general nitrogen turnover of Amino Acids in the mammalian body. For instance, when ¹⁵N-labeled amino acids were administered to rats, no label was detected in threonine [255, 256]. Available data indicate the existence of two pathways for threonine degradation. One of them resembles the dehydration and deamination reactions of Serine (p. 331) and is presumably catalyzed by the same enzyme:

Class="center">

¹ It is now known that in the course of this conversion, homoserine is first phosphorylated (at the expense of ATP) to yield O-phosphohomoserine; under the action of the pyridoxal enzyme threonine synthetase, this compound is converted into threonine via the elimination of a phosphoric acid molecule followed by The addition of a Water molecule. — Ed. note.

This mechanism is consistent with findings that in rat Liver preparations, DL-threonine labeled with N¹⁵ and C¹⁴ is converted into L-a-aminobutyric acid [257]. Threonine is likely converted into a-ketobutyric acid, which subsequently undergoes stereospecific Transamination to form L-a-aminobutyric acid. The Oxidative Deamination of D-threonine can yield the same product.

Another pathway of threonine degradation was discovered by Braunstein and Vilenkina. These authors observed The formation of Glycine and acetaldehyde from threonine in liver and Kidney preparations from various animals [258]:

It is noteworthy that in this system, allo-threonine serves as a more active substrate than threonine [185, 258, 259]. The enzymatic reaction appears to be weakly reversible, although the steric configuration of the product formed in the reverse reaction has not been established [261]. The names "glycinogenase" [258] and "hydroxyamino acid aldolase" [262] have been proposed for The enzyme catalyzing the Cleavage of threonine into glycine and acetaldehyde. The Mechanism of threonine cleavage was studied by Snell and coworkers [260, 263], who described the non-enzymatic reversible breakdown of threonine in the presence of pyridoxal and metal salts [260, 263]. Pyridoxal phosphate was shown to function as the coenzyme in the enzymatic reaction [238]¹.

The Enzymatic cleavage of ß-phenylserine isomers by a purified rat liver protein fraction has been described [264]. The erythro-L-isomer is cleaved 9 times faster than the threo-isomer and 7 times faster than allo-threonine. The products of the enzymatic cleavage of erythro-β-phenyl-L-serine are benzaldehyde and glycine. Interestingly, as early as 1914, Knoop [265] observed an increased urinary excretion of hippuric acid in dogs fed ß-phenylserine. Knoop hypothesized that ß-phenylserine splits into glycine and benzoic acid.

In experiments on rats using threonine labeled with N¹⁵ and C¹⁴ in the methyl group, it was found that roughly 1/5 to 1/3 of the dietary threonine ingested is cleaved into glycine and acetic acid [256]. The latter is presumably formed through The oxidation of acetaldehyde. The same study noted that following the administration of ¹⁵N-leucine, only trace amounts of ¹⁵N were incorporated into threonine, which agrees with earlier findings. However, the presence of some leucine nitrogen in the threonine molecule points to a low level of de novo threonine synthesis in the animal body or to the partial reversibility of its degradation reactions. Alternatively, this observed isotopic nitrogen incorporation into threonine might be due to intestinal microflora activity.

¹ The involvement of pyridoxal phosphate in the enzymatic cleavage of threonine into glycine and acetaldehyde was established in 1953 by Braunstein and Vilenkina (Usp. Sovrem. Biol., 36, 275, 1953). — Ed. note.

Fig. 11. Summary scheme of threonine transformations.

There is no evidence proving that threonine can be synthesized from homoserine in the mammalian Organism. In this context, It is interesting to note that experiments with liver preparations demonstrated the Formation of the homoserine-related keto acid (a-keto-y-hydroxybutyric acid) from pyruvic acid and formaldehyde [266]:

Transamination of this keto acid has also been detected [267].