Homocysteine Thiolactone: Biology and Chemistry

Abstract

Homocysteine thiolactone is a five-membered cyclic thioester of amino acid homocysteine. It is generated from homocysteine as a result of an error-editing reaction, principally, of methionyl-tRNA synthetase. An elevated level of homocysteine thiolactone is associated with cardiovascular diseases, strokes, atherosclerosis, neurological abnormalities, etc., presumably because it reacts to the side chain of protein lysine causing protein damage and autoimmune responses. It is not only an important metabolite but also a versatile building block for organic and bioorganic synthesis. This entry contains data on the homocysteine thiolactone formation, metabolism, toxicity mechanism in vivo, and the bioorganic chemistry applications as a powerful synthetic tool in polymer science, sustainable materials development, and probes.

Application of W-band19F electron nuclear double resonance (ENDOR) spectroscopy to distance measurement using a trityl spin probe and a fluorine label

“…This process alters a protein's function, stability, oligomerization, and aggregation as well as amyloid transformation. 31,33 Moreover, HSA is one of the main targets of N -homocysteinylation in humans. Such a process decreases the α-helix content of albumin, 36 influences its reducing properties, promotes the formation of free radicals, 35,36 affects susceptibility to proteolysis 52 and oligomerization, and drives amyloidal transformation.…”

“…One of the major albumin post-translational modifications is N -homocysteinylation. 31–33 The process involves a metabolite called homocysteine thiolactone (HTL), which acrylates lysine hyper-reactive residues in a protein (Scheme 1). It can affect protein functions and oligomerization properties and plays a crucial part in the progression of many disorders/diseases such as atherosclerosis, stroke, Parkinson's and Alzheimer's diseases, and cancer.…”

Patient Stratification in Sepsis: Using Metabolomics to Detect Clinical Phenotypes, Sub-Phenotypes and Therapeutic Response

“…Lin et al reported that patients with sepsis-induced AKI had higher circulating phenylalanine than patients without and that this could also predict the risk of later kidney dysfunction [ 21 ]. In addition, patients with AKI showed a reduction in 2-coumaranone [ 21 ] which has been associated with low vascular tone and which has some structural similarities with hydrolysed homocysteine thiolactone [ 139 ], a risk factor for arteriosclerosis, stroke and cardiovascular disease [ 140 ]. Although promising, no metabolomic approaches to predict organ dysfunction have reached clinical practice.…”

Serum Albumin for Magnetic Nanoparticles Coating

“…The thiolactone ring-opening results in releasing a free sulfhydryl group, which can be used for further modification (Figure 3). Therefore, this reaction can introduce two different residues into the polymer chain [92]. Using N-substituted HTL derivatives, several probes for the glioma 19 F-MRI [84,90] and 1 H-MRI based [91] on HSA were synthesized.…”