2,5,5-Trimethylthiazolidine-4-carboxylic acid, a D(-)-penicillamine-directed pseudometabolite of ethanol. Detoxication mechanism for acetaldehyde.
A directed detoxication mechanism for acetaldehyde (AcH) is described wherein ethanol-derived AcH, circulating in the blood of rats given ethanol-1-14C and disulfiram or pargyline, was sequestered by condensation with administered D(-)-penicillamine (1). The product of this condensation, 2,5,5-trimethylthiazolidine-4-carboxylic acid (3), which was excreted in the urine without acetyl conjugation, was quantitatively determined by inverse isotope dilution measurements. Acetylation of the urine permitted the isolation of the corresponding N-acetyl derivative in crystalline form. The chirality of 3 was deduced by NMR analysis to be 72% 2S, 4S and 28% 2R, 4S. Although acetylation selectively acetylated the predominant isomer, this acetylated derivative was identical in all respects with a chemically synthesized product. This suggests that the in vivo condensation of AcH and 1 is not enzyme mediated.
D000079:Acetaldehyde / Q000097:blood / Q000378:metabolism*; D000107:Acetylation; D000818:Animals; D000431:Ethanol / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008297:Male; D008722:Methods; D010396:Penicillamine / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D051381:Rats; D013237:Stereoisomerism; D013844:Thiazoles / Q000378:metabolism* / Q000652:urine
D013844:Thiazoles; D000431:Ethanol; D010396:Penicillamine; D000079:Acetaldehyde