L-Cysteine is the central compound in sulfur metabolism in the human body. In proteins the formation of disulfide bonds between the thiol groups of cysteine plays an important role for tertiary structure and enzymatic activity; cysteine is however always incorporated in the polypeptide chain as cysteine. L-Cysteine is degraded to pyruvate in two steps: one is removal of sulfur and the other is a transamination. Cysteine can be metabolized to form taurine and carbon dioxide through the cysteinsulfinate pathway, where the initial step is oxidation of cysteine to cysteine sulfinate. This step is catalyzed by cysteine dioxygenase. Cysteine sulfinate may then be decarboxylated to form taurine or it may be metabolized via the putative intermediate beta-sulfinylpyruvate to pyruvate and sulfite and then to carbon dioxide and sulfate.
Amino acid catabolism is essential for adjusting pool sizes of free amino acids and takes part in energy production as well as nutrient remobilization. The carbon skeletons are generally converted to precursors or intermediates of the tricarboxylic acid cycle. In the case of cysteine, the reduced sulfur derived from the thiol group also has to be oxidized in order to prevent accumulation to toxic concentrations. Here we present a mitochondrial sulfur catabolic pathway catalyzing the complete oxidation of L-cysteine to pyruvate and thiosulfate. After transamination to 3-mercaptopyruvate the sulfhydryl group from L-cysteine is transferred to glutathione by sulfurtransferase 1 and oxidized to sulfite by the sulfur dioxygenase ETHE1. Sulfite is then converted to thiosulfate by addition of a second persulfide group by sulfurtransferase 1. This pathway is most relevant during early embryo development and for vegetative growth under light limiting conditions. Characterization of a double mutant produced from Arabidopsis thaliana T-DNA insertion lines for ETHE1 and sulfurtransferase 1 revealed that an intermediate of the ETHE1 dependent pathway, most likely a persulfide, interferes with amino acid catabolism and induces early senescence.
Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.
IDENTIFICATION AND USE: Cysteine forms white or colorless crystals. It is used in biochemical and nutrition research, as a reducing agent in bread doughs (up to 90 ppm). It is also used as flavor enhancer and medication, including veterinary medication. HUMAN EXPOSURE AND TOXICITY: Cysteine solution (3%) was not irritating for human eyes. ANIMAL STUDIES: A single ocular application of L-cysteine to rabbits at a dose of 0.1 g produced slight irritant effects, which were fully reversible within 48 hours. The single dermal application of L-cysteine to three rabbits at a dose of 0.5 g showed neither irritant nor corrosive effects. Decreased litter size observed in rats receiving high-dose cysteine, which was related to the degeneration and/or death of ovulated unfertilized oocytes and embryos with changes in the zona pellucida, which was already affected in the ovary. Pregnant mice and rats were treated s.c. with 1.2 mg per g on the last day of pregnancy and brain degeneration was observed one day later in the fetus. L-Cysteine is considered to be non-mutagenic in the HPRT locus using V79 cells of the Chinese Hamster. L-Cysteine did not induce structural chromosomal aberrations in the V79 Chinese hamster cell line. ECOTOXICITY STUDIES: The objective of the study was to determine the effects of cysteine on postthaw sperm motility, duration of sperm motility, DNA damage, and fertility in the common carp (Cyprinus carpio). Supplementation with cysteine increased the fertilization and hatching rate and decreased DNA damage.
Uremic toxins such as cysteine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869).
Although classified as a non-essential amino acid cysteine may be essential for infants, the elderly, and individuals with certain metabolic disease or who suffer from malabsorption syndromes. Cysteine can usually be synthesized by the human body under normal physiological conditions if a sufficient quantity of methionine is available. Due to the ability of thiols to undergo redox reactions, cysteine has antioxidant properties. Cysteine's antioxidant properties are typically expressed in the tripeptide glutathione, which occurs in humans as well as other organisms. The systemic availability of oral glutathione (GSH) is negligible; so it must be biosynthesized from its constituent amino acids, cysteine, glycine, and glutamic acid. Glutamic acid and glycine are readily available in the diets of most industrialized countries, but the availability of cysteine can be the limiting substrate. Cysteine is also an important source of sulfide in human metabolism. The sulfide in iron-sulfur clusters and in nitrogenase is extracted from cysteine, which is converted to alanine in the process. In a 1994 report released by five top cigarette companies, cysteine is one of the 599 additives to cigarettes. Its use or purpose, however, is unknown, like most cigarette additives. Its inclusion in cigarettes could offer two benefits: Acting as an expectorant, since smoking increases mucus production in the lungs; and increasing the beneficial antioxidant glutathione (which is diminished in smokers).
Thiabendazole-based Rh(III) and Ir(III) biscyclometallated complexes with mitochondria-targeted anticancer activity and metal-sensitive photodynamic activity
摘要：
Two pairs of Rh(III) and Ir(III) biscyclometallated complexes with thiabendazole (L-1), named [Ir-a]Cl and [Rh-a]a, and N-benzyl-thiabendazole (L-2), named [Ir-b]Cl and [Rh-b]Cl, have been designed and synthesized to explore the photophysical and biological effects that arise from changing both the metal center and the ancillary ligand. In the dark, the four metal complexes exhibit greater cytotoxicity than cisplatin against human colon (SW480) and human lung (A549) adenocarcinoma cell lines. Moreover, the pair of complexes bearing the ligand L-2 is markedly more cytotoxic and present higher uptake values than complexes with L-1, thereby their biological properties were studied further to determine their mechanism of action. Interestingly, in spite of the different metal center both the [Ir-b]Cl and [Rh-b]al complexes are responsible for the loss of mitochondrial functionality and the activation of apoptotic cell death pathways. Moreover, the photodynamic activity of the four complexes, [Ir-a,b]Cl and [Rh-a,b]Cl, was tested using visible blue light (460 nm) under soft irradiation conditions (20 min, 5.5 mW cm(-2)). While the Rh complexes are not photopotentiated, the phototoxicity index (IC50 non-irradiated/IC50 irradiated) of [Ir-a]Cl and [Ir-b]Cl complexes was 15.8 and 3.6, respectively. We also demonstrate that only the Ir derivatives are capable of photocatalyzing the oxidation of S-containing 1. -amino acids under blue light irradiation, [Ir-a]Cl being more active than [Ir-b]Cl, which provides a reasonable mechanism for their biological action (oxidative stress could be selectively promoted through a photocatalytic action) upon irradiation. This different PDT behaviour depending on the metal center and the ancillary substituent may be useful for future rational design of metal-based photosensitizers. (C) 2018 Published by Elsevier Masson SAS.
Electrochemical Studies of Poly(mercaptohydroquinone) and Poly(mercapto-p-benzoquinone) Films Prepared by Electrochemical Polymerization. VI.Electroreduction of L-Cystine on Thiolates Fixed in the Polymer Film
The present invention provides new derivatives having the general formula (I), (I) wherein R1, R2, R3, R4, R5, R6, R7, X1, X2, X3, X4, and X5are as defined herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.
Of Thiols and Disulfides: Methods for Chemoselective Formation of Asymmetric Disulfides in Synthetic Peptides and Polymers
作者：Olga Schäfer、Matthias Barz
DOI：10.1002/chem.201800681
日期：2018.8.22
media to form S−C bonds, possibilities for the chemoselective formation of asymmetric disulfides have been less approached. Focusing on bioreversibility in conjugation chemistry, the formation of disulfide bonds is highly desirable for the attachment of thiol‐containing bioactive agents to proteins or in cross‐linking reactions, because disulfide bonds can combine stability in blood with degradability inside
Novel S-bridged dinuclear cobalt(III) complexes having different absolute configurations in [Co(didentate-N,S)3] moieties, Λ- and Δ-[CoCo(didentate-N,S)3}(D-pen-N,O,S)]+ or 2− (didentate = 2-aminoethanethiolate (aet), L-cysteinate (L-cys), and D-penicillaminate (D-pen)), were prepared stereospecifically. The dinuclearizing reaction of ΔLLL-fac(S)-[Co(L-cys-N,S)3]3− with [CoCl(NH3)5]2+ and D-penicillaminate
Reactivity and selectivity of the reaction of O,O-diethyl 2,4-dinitrophenyl phosphate and thionophosphate with thiols of low molecular weight
作者：J. G. Santos、M. E. Aliaga、K. Alarcón、A. Torres、D. Céspedes、P. Pavez
DOI：10.1039/c6ob00918b
日期：——
triester derivatives, (ii) a kinetic control product by sulfhydryl attack of thiols was observed in the reactions of both triesters with Cys and Hcys, followed by an intramolecular amine attack leading to a thermodynamic control product. The kineticstudy leads to the proposal of Meisenheimer complex formation and then proton transfer to the reaction media as the mechanism of these reactions.
Nucleophilic reactivity of thiolate, hydroxide, and phenolate ions toward a model<i>O</i><sup>2</sup>-arylated diazeniumdiolate prodrug in aqueous and cationic surfactant media
作者：Matthew S. Ning、Stacy E. Price、Jackie Ta、Keith M. Davies
DOI：10.1002/poc.1607
日期：——
and in solutions of cationic DOTAP vesicles. Second-order rate constants in buffered aqueous solutions (k(RS(-) ) = 3.48 - 30.9 M(-1)s(-1); 30 degrees C) gave a linear Bronsted plot (beta(nuc) = 0.414 +/- 0.068) consistent with rate-limiting S(N)Ar nucleophilic attack by thiolate ions. Cationic DOTAP vesicles catalyze the thiolysis reactions with rateenhancements between 11 and 486-fold in Tris-HCl
