PubMed · 7020370
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P F Urban, P Reichert, P Mandel. 1981. Taurine metabolism and function.. https://pubmed.ncbi.nlm.nih.gov/7020370/
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PURPOSE OF REVIEW: This review discusses the recent evidence indicating that sulfur amino acid metabolism in gastrointestinal tissues may be linked to human health and gut disease. RECENT FINDINGS: Studies indicate that the gastrointestinal tract metabolizes 20% of dietary methionine and that its main metabolic fate is transmethylation to homocysteine and transsulfuration to cysteine. The gastrointestinal tract accounts for approximately 25% of whole-body transmethylation and transsulfuration and is a site of net homocysteine release. The production of homocysteine within the intestinal mucosa may contribute to the inflammatory response and endothelial cell dysfunction in patients with inflammatory bowel disease. Studies also show that the availability of S-adenosylmethionine as a precursor for methylation reactions and polyamines plays a key role in epigenetic DNA methylation, gene expression and colon carcinogenesis. Cysteine derived from the diet and methionine transsulfuration is a functional constituent of antioxidant systems and impacts several elements of redox status that regulate epithelial intracellular signaling, proliferation and survival. SUMMARY: Further studies are warranted to establish how local production of homocysteine, S-adenosylmethionine and antioxidants contributes to the development of gastrointestinal diseases and whether dietary intervention with folate and cysteine is an efficacious approach to prevention and treatment.
The "amitochondriate" protozoan parasites of humans Entamoeba histolytica, Giardia intestinalis, and Trichomonas vaginalis share many biochemical features, e.g., energy and amino acid metabolism, a spectrum of drugs for their treatment, and the occurrence of drug resistance. These parasites possess metabolic pathways that are divergent from those of their mammalian hosts and are often considered to be good targets for drug development. Sulfur-containing-amino-acid metabolism represents one such divergent metabolic pathway, namely, the cysteine biosynthetic pathway and methionine gamma-lyase-mediated catabolism of sulfur-containing amino acids, which are present in T. vaginalis and E. histolytica but absent in G. intestinalis. These pathways are potentially exploitable for development of drugs against amoebiasis and trichomoniasis. For instance, L-trifluoromethionine, which is catalyzed by methionine gamma-lyase and produces a toxic product, is effective against T. vaginalis and E. histolytica parasites in vitro and in vivo and may represent a good lead compound. In this review, we summarize the biology of these microaerophilic parasites, their clinical manifestation and epidemiology of disease, chemotherapeutics, the modes of action of representative drugs, and problems related to these drugs, including drug resistance. We further discuss our approach to exploit unique sulfur-containing-amino-acid metabolism, focusing on development of drugs against E. histolytica.
Photooxidation of sulfur-containing amino acids and derivatives readily occurs upon visible-light irradiation in the presence of flavins. The sulfur moiety seems pivotal for interaction, as was determined from kinetic analyses using laser flash photolysis spectroscopy. After photooxidation, the resulting radical intermediates were characterized by addition to a spin trap, followed by electron paramagnetic resonance spectroscopy and evaluation of the coupling constants. The presence of the proposed radical intermediates was strongly supported by the identification of the reaction products using mass spectrometry. Accordingly, feasible degradation pathways for various sulfur-containing amino acids and derivatives were proposed. It was finally proven that flavin-induced photoproduction of sulfhydryl radicals and recombination with a 3-methylbut-2-enyl radical, derived from the photodegradation of hop-derived isohumulones, are decisive in the formation of beer lightstruck flavor.