Salsolinol-1-carboxylic acid

Oxidative decarboxylation of salsolinol-1-carboxylic acid to 1,2-dehydrosalsolinol: evidence for exclusive catalysis by particulate factors in rat kidney.[Pubmed:3369867]

Arch Biochem Biophys. 1988 May 15;263(1):86-95.

The decarboxylation of Salsolinol-1-carboxylic acid (1-methyl-6,7-dihydroxy-1,2,3,4- tetrahydroisoquinoline-1-carboxylic acid), a novel endogenous catecholic adduct of dopamine and pyruvic acid, was examined in nuclei-free homogenates of rat liver, whole brain, and kidney, as well as in buffer only. Liquid chromatographic analysis of incubations for varying times (30 min to 5 h) showed that the tetrahydroisoquinoline substrate decarboxylated oxidatively, forming one product, 1-methyl-6,7-dihydroxy-3,4-dihydroisoquinolines (1,2-dehydrosalsolinol). No salsolinol was apparent, even with added NADPH. In buffer, decarboxylation occurred by an apparent oxygen radical-mediated process: it was stimulated by cupric ion or elevated pH, and was suppressed by EDTA, superoxide dismutase, metal ion removal with Chelex-100, or low pH (less than 6). In liver or brain, the conversion was qualitatively and quantitatively similar to that in buffer; thus there was no evidence for enzyme involvement. In kidney, however, dehydrosalsolinol formation was significantly greater than that in liver, brain, or buffer, and preboiling reduced it nearly to buffer values. The heat-labile kidney activity, displaying a pH maximum ca. 9, was localized in the particulate fractions. It was blocked completely by N-ethylmaleimide. Added superoxide dismutase was only slightly inhibitory; catalase and dimethyl sulfoxide, a hydroxyl radical trap, were uneffective. Lack of inhibition by indomethacin ruled against peroxidative involvement of kidney prostaglandin synthetase. Physiological amounts of a cofactor for amino acid decarboxylases, pyridoxal-5'-phosphate, also had no effect. The oxidative decarboxylation of 1-carboxylated salsolinol by kidney fractions appears mainly due to a sulfhydryl-containing particulate factor unique to or relatively concentrated in that organ. Its identity, substrate specificity, and possible significance, particularly in alcoholism, where elevated Salsolinol-1-carboxylic acid levels have been reported, remain to be ascertained.

Oxidation chemistry of the endogenous central nervous system alkaloid salsolinol-1-carboxylic acid.[Pubmed:8421275]

J Med Chem. 1993 Jan 8;36(1):11-20.

The oxidation chemistry of Salsolinol-1-carboxylic acid (1), an alkaloid endogenous to the central nervous system which is elevated as a result of ethanol consumption, has been studied by electrochemical approaches at pH 7.0 in aqueous solution. The first voltammetric oxidation peak of Ia of 1 at pH 7.0 occurs at Ep = +0.116 V, indicating that this alkaloid is a very easily oxidized compound. The peak Ia reaction is a 2e-2H+ oxidation of 1 to 1,2,3,4-tetrahydro-1-methyl-1-carboxy-6,7-isoquinolinedione (8), which rapidly decarboxylates (k > 10(3) s-1) to give predominantly the quinone methide tautomer of 3,4-dihydro-1-methyl-6,7-isoquinolinediol (2). The latter compound is responsible for the second observed oxidation peak IIa observed with 1. This peak is a 2e oxidation of 2 to a quinoid intermediate (9) which can either be attacked by water to yield 3,4-dihydro-1-methyl-5,7-dihydroxyisoquinolin-6-one (13b) (which is readily further oxidized to 3,4-dihydro-1-methyl-5-hydroxyisoquinoline-6,7-dione (3)) or aromatizes to yield 1-methyl-6,7-isoquinolinediol (4). Preliminary in vivo experiments have revealed that 2 and 13b are behavioral toxins when injected into the brains of laboratory mice. The in vitro oxidation reactions of 1 and 2 reported here might be of relevance to the neurodegenerative, behavioral, and addictive consequences of chronic alcoholism.

Identification and quantification of 1-carboxysalsolinol and salsolinol in biological samples by gas chromatography--mass spectrometry.[Pubmed:4066844]

J Chromatogr. 1985 Sep 13;343(1):1-8.

1-Carboxysalsolinol was found to be present in rat striatum, human urine and caudate nucleus of post mortem human brain, according to capillary column gas chromatographic retention times and selected ion monitoring of the hexafluoropropionyl ester pentafluoropropyl derivative. Simultaneous quantification of 1-carboxysalsolinol and salsolinol was performed in biological samples using deuterium labelled internal standards. In human urine, the precision of the method was +/- 7.1% (coefficient of variation, n = 25) for 1-carboxysalsolinol at 15 pmol/ml and +/- 8.5% for salsolinol at 10 pmol/ml. According to enzymatic hydrolysis, 68% of 1-carboxysalsolinol was found as conjugates in urine, and the corresponding figure for salsolinol was 92%. In human caudate nucleus, the amounts of 1-carboxysalsolinol were found to be significantly greater in brains from alcoholics, who at autopsy had ethanol present in the blood, whereas alcoholics without blood ethanol levels at autopsy had significantly lower concentrations of salsolinol.