Occurrence of 2-methylthiazolidine-4-carboxylic acid, a condensation product of cysteine and acetaldehyde, in human blood as a consequence of ethanol consumption

Abstract

Acetaldehyde is a strongly electrophilic compound that is endogenously produced as a first intermediate in oxidative ethanol metabolism. Its high reactivity towards biogenic nucleophiles has toxicity as a consequence. Acetaldehyde readily undergoes a non-enzymatic condensation reaction and consecutive ring formation with cysteine to form 2-methylthiazolidine-4-carboxylic acid (MTCA). For analytical purposes, N-acetylation of MTCA was required for stabilization and to enable its quantification by reversed-phase chromatography combined with electrospray ionization-tandem mass spectrometry. Qualitative screening of post mortem blood samples with negative blood alcohol concentration (BAC) mostly showed low basal levels of MTCA. In BAC-positive post mortem samples, but not in corresponding urine specimens, strongly increased levels were present. To estimate the association between ethanol consumption and the occurrence of MTCA in human blood, the time curves of BAC and MTCA concentration were determined after a single oral dose of 0.5 g ethanol per kilogram of body weight. The blood elimination kinetics of MTCA was slower than that of ethanol. The peak concentration of MTCA (12.6 mg L(-1)) was observed 4 h after ethanol intake (BAC 0.07‰) and MTCA was still detectable after 13 h. Although intermediary acetaldehyde scavenging by formation of MTCA is interesting from a toxicological point of view, lack of hydrolytic stability under physiological conditions may hamper the use of MTCA as a quantitative marker of acetaldehyde exposure, such as resulting from alcohol consumption.

One-pot non-enzymatic formation of firefly luciferin in a neutral buffer from p-benzoquinone and cysteine

“…Indeed, we detected hydroquinone in 24.1% yield after the one-pot reaction. It has been reported that the condensation of acetaldehyde with cysteine in water give 2-methylthiazolidine-4-carboxylic acid while retaining the original configuration of the cysteine stereocenter 31 , and that 2-thiazolines can be synthesized from 2-thiazolidines by Ru/PPh 3 or Ru/TMEDA-catalysed oxidation with TBHP at ambient temperature 32 . These results are consistent with the fact that the original configuration of the cysteine stereocenter was retained through the formation of thiazoline moiety in the one-pot reaction ( Fig.…”

Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde: results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis

“…[33] MTCA is an endogenous product that is detected in the blood after a moderate ethanol dose (0.5 g/kg). [34] Furthermore, it has been shown that MTCA can serve as a prodrug for L-cysteine and thus protect mice against acetaminophen toxicity. [35] Under the present study conditions, sufficiently high L-cysteine levels for acetaldehyde neutralisation were achieved in the gastric juice at 10-20 min after L-cysteine (Acetium) capsule intake.…”

Liquid-Chromatographic Methods for Carboxylic Acids in Biological Samples

“…DMB was developed to improve the sensitivity of fluorescence detection, and has a structure similar to that of OPD. As shown in Figure 11, we quantified α-keto acids in chronic myeloid leukemia cells to investigate the role of BCAT1 [73]. The concentrations of six α-keto acids were between 1.55 and 316 pmol per 106 cells and LODs were within 1.3 and 5.4 nM, being three-fold higher than that of OPD.…”

“…2-Methylthiazolidine-4-carboxylic acid (MTCA, Figure 14) is produced by the reaction of acetaldehyde and cysteine, and it is a biomarker for recent alcohol consumption. MTCA has been derivatized with acetic anhydride and then analyzed by reversed-phase LC-ESI-MS [73]. Free MTCA is unstable under physiological conditions as it is readily hydrolyzed.…”