Introduction

Phenylalanine is an aromatic amino acid which besides its hydroxylation to tyrosine and its degradation to phenylketonic acids is substrate of L-aromatic amino acid decarboxylase by sensitive methods in various tissues (including brain) of untreated animals and in the brain and urine of humans. Phenylalanine, α-amino-β-phenylpropionic acid, include DL- phenylalanine (Figure 1),L-phenylalanine, D- phenylalanine, is a kind of amino acid. L-phenylalanine can be used to synthesis new medicament and sweetener. D-phenylalanine has analgesic activity. Recently, DL-phenylalanine has been proven to have excellent effects such as antidepressant properties and weight loss and so on.

Metabolism of DL-Phenylalanine by Aspergillus niger

A fungus capable of degrading DL-phenylalanine was isolated from the soil and identified as Aspergillus niger. It was found to metabolize DL-phenylalanine by a new pathway involving 4-hydroxymandelic acid. 1-Amino acid oxidase and L-phenylalanine: 2-oxoglutaric acid aminotransferase initiated the degradation of D- and L-phenylalanine, respectively. Both phenylpyruvate oxidase and phenylpyruvate decarboxylase activities could be demonstrated in the cell-free system. Phenylacetate hydroxylase, which required reduced nicotinamide adenine dinucleotide phosphate, converted phenylacetic acid to 2-and 4-hydroxyphenylacetic acid. Although 4-hydroxyphenylacetate was converted to 4-hydroxymandelate, 2-hydroxyphenylacetate was not utilized until the onset of sporulation. During sporulation, it was converted rapidly into homogentisate and oxidized to ring-cleaved products. 4-Hydroxymandelate was degraded to protocatechuate via 4-hydroxybenzoylformate, 4-hydroxybenzaldehyde, and 4-hydroxybenzoate.[1]

DL-Phenylalanine in Depressed Patients

In an open study DL-phenylalanine in doses from 75-200 mg/day was administered to 20 depressed patients for 20 days.Patients were classified according to the International Classification of Diseases (ICD).The AMP system, the Hamilton depression scale and the yon Zerssen self rating questionnaire were used for documentation of psychopathological, neurologic and somatic changes. In addition a global clinical impression was agreed upon by experienced psychiatrists.At the end of the trial 12 patients (8 with complete, 4 with good response) could be discharged without any further treatment. 4 patients with partially untypical depressions experienced mild to moderate responses,whereas 4 patients did not respond at all to the phenylalanine administration. Depressive "core symptoms" as depressed mood, retardation and/or agitation were preferentially, anxiety and sleep disturbances moderately and hypochondriasis and compulsiveness were not influenced. It is concluded that dl-phenylalanine might have substantial antidepressant properties and that further more controlled investigations are warranted.[2]

DL-Phenylalanine Versus Imipramine[3]

In a double-blind study, DL-phenylalanine (150-200 mg/24 h) or imipramine (150-200 mg/24 h) was administered to 40 depressed patients(20 patients in each group) for 30 days. Diagnoses were established according to the International Classificationof Diseases (ICD). The AMP system, the Hamilton Depression Scale and the Bf-S self rating questionnaire were used to document psychopathological, neurologic, and somatic changes.

Twenty-seven patients (14 on imipramine, 13 on phenylalanine) completed the 30-day trial. No statistical difference could be found between these two drug treatment groups (Student's t-test) using the Hamilton Depression Scale and the Bf-S self rating questionnaire. Ratings for anxiety were significantly lower in the imipramine group on days 10 and 20, but not on day 30; in addition, sleep disturbances were more influenced by imipramine on days 1, 5,and 10, but not on days 20 and 30.Separate analysis of psychopathological syndromes as somatic depressive syndrome and retarded depressive syndrome did not show a group difference (0.05 level of significance using a two-way analysis of variance).Retrospective inspection of the additional drug administration revealed an equal need for sleeping medication for both groups, although no sedative properties of DL-phenylalanine have ever been noticed.No information exists regarding the mechanism of action of DL-phenylalanine. It has been shown that this compound readily passes the blood-brain barrier, where its decarboxylated product, phenethylamine, which has been shown to possess amphetamine-like properties, might be the active component. In addition, infusion of this amino acid raises growth hormone levels in the plasma of healthy volunteers.

In conclusion, clinical results of this and other studies suggest an antidepressant efficacy of DL-phenylalanine, which, with certain modifications, seems to equal that of the tricyclic antidepressant imipramine. However, certain methodological considerations still warrant a careful interpretation.

References

[1]Kishore G, Sugumaran M, Vaidyanathan CS. Metabolism of DL-(+/-)-phenylalanine by Aspergillus niger. J Bacteriol. 1976;128(1):182-191. doi:10.1128/jb.128.1.182-191.1976

[2]Beckmann H, Strauss MA, Ludolph E. Dl-phenylalanine in depressed patients: an open study. J Neural Transm. 1977;41(2-3):123-134. doi:10.1007/BF01670277

[3]Beckmann H, Athen D, Olteanu M, Zimmer R. DL-phenylalanine versus imipramine: a double-blind controlled study. Arch Psychiatr Nervenkr (1970). 1979;227(1):49-58. doi:10.1007/BF00585677