Decarboxylation of 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acids in brain homogenate and catalysis by pyridoxal-5'-phosphate

[Carboxyl-14C] labelled 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (I) and 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (II) were synthesized and their decarboxylation was studied in mouse brain homogenate and buffer. The decarboxylation rates of (I) and (II) in the homogenate were about 6-fold and 4-fold, respectively, as compared with the rates in phosphate buffer. The increase could not be prevented by preheating the homogenate, but was partially abolished by addition of 1 mM EDTA. The decarboxylation was increased dose-dependently when pyridoxal-5'-phosphate was included in the buffer, 400 microM being sufficient to exceed the rate in homogenate for both (I) and (II). Mass spectrometric examination of the decarboxylation products indicated that both (I) and (II) were degraded mainly to corresponding 1,2,3,4-tetrahydro-beta-carbolines, but some 3,4-dihydro analogues also were detectable. In conclusion, the results outline a way through which these pharmacologically active beta-carbolines are readily formed under conditions that may be regarded as physiological.