Compounds reaction with methionine

Direct evidence of the reaction of PAN with sulfhydryl compounds has since been obtained (PAN at 115 ppm for 1-10 min). - In the reaction with glutathione, the major products are oxidized glutathione (disulfide) and 5-acetylglutathione. Other sulfhydryl compounds (e.g., coenzyme A, lipoic acid, and cysteine) yield only oxidation products, with no evidence of 5-acetylation. However, acetylation reactions have been observed with alcohols and amines. Sulfur compounds other than thiols can undergo oxidation by PAN methionine is converted to methionine sulfoxide, and oxidized lipoic acid (disulfide) is converted to sulfoxide. 

The high affinity of many platinum compounds for sulfur and the availability of many sulfur-containing biomolecules have raised the question whether Pt-sulfur biomolecule interactions could serve as a drug reservoir for platination at DNA, necessary for the antitumor activity of cis-Pt. Two reaction paths are possible, i.e., spontaneous release of plantinum from the sulfur, or nucleophilic displacement of platinum from sulfur by guanine (N7), for example. At the moment, there is no real evidence for the existence of such reactivation mechanisms. In fact, it has been reported that Pt-protein interactions in the plasma (albumin) are not reversible under normal conditions (161, 165). Further, a mixture of cis-Pt-methionine products does not show antitumor properties (166), indicating no induced platination of DNA. More research is required to investigate the existence of a reactivation mechanism. However, it is predicted that if such a reactivation phenomenon is operational, the most likely candidate is the labile Pt-methionine bond, as has been shown by its rapid reaction with Naddtc, STS, and thiourea (vide supra) (131). 

Amino, hydroxyl and thiol groups in foreign compounds may undergo methylation in vivo (figure 4,66) in the same manner as a number of endogenous compounds. The methyl donor is S-adenosyl methionine formed from methionine and ATP (see Chapter 7, figure 7.41) and so again it is a type 1 reaction with an... 

The reaction mixture (final volume 0.34 ml) contained (in /umol and including compounds added with the enzyme) potassium phosphate, pH 6.3, 102 Tris, pH 7.6, 5 sucrose, 13 GSH, 16 2-mercaptoethanol, 0.7 Na EDTA, 0.5. Methyl donors were added at the specified final concentrations. The various stereoisomeric forms of S-adenosylmethionine were prepared as described by de la Haba el al. (1959) using adenosylmethionine cyclotransferase (E.C. 2.5.1.4) to resolve (/(S)-S-adenosyl-L-methionine to (f )-5-adenosyl-L-methionine. The reaction was started by addition of enzyme dissolved in Tris buffer, pH 7.6, 25 mM, containing Na EDTA, 1 mM and 2-mercaptoethanol, 7 mM, and partially purified from an extract of cabbage leaves by successive ammonium sulfate precipitation (45-60% saturation), gel filtration (Sephadex G-25) and DEAE-cellulose column chromatography. After incubation at 26°C for 1 h, each reaction mixture was diluted with 0.76 ml cold water, and a 1.0 ml aliquot was immediately added to a column of Dowex-50(NHJ) 1 x 3 cm. Unreacted [ C]methionine was removed by washing the column with 25 ml water. The 5-[" C]methylmethionine sulfonium salt was then eluted with 8 ml 0.6 N NH OH. Radioactivity was determined by scintillation spectrophotometry (Mudd et al., 1965). A blank of 540 cpm has been subtracted from each value. The low activity with (R)-5-adenosyl-L-methionine may have been due to the presence of a small residual amount of (5)-5-adenosyl-L-methionine (de la Haba eta/., 1959). 

The thermal generation of flavor is a very essential process for the "taste" of many different foodstuffs, e.g. cocoa, coffee, bread, meat. The resulting aromas are formed through non-enzymatic reactions mainly with carbohydrates, lipids, amino acids (proteins), and vitamins under the influence of heat. Thiamin (vitamin B ) and the amino acids, cysteine and methionine, belong to those food constituents which act as flavor precursors in thermal reactions. The role of thiamin as a potent flavor precursor is related to its chemical structure which consists of a thiazole as well as a pyrimidine moiety. The thermal degradation of this heterocyclic constituent leads to very reactive intermediates which are able to react directly to highly odoriferous flavor compounds or with degradation products of amino acids or carbohydrates. 

Dicobalt-hexacarbonyl-alkyne complexes are another class of organometallic compounds with good stability imder physiological conditions. Complexation of the alkyne proceeds smoothly under mild conditions by reaction with Co2(CO)g imder loss of two molecules of CO [79]. The applicability of this reaction to peptides was shown by Jaouen and coworkers by the reaction of Co2(CO)g with protected 2-amino-4-hexynoic acid (Aha) and dipeptides thereof (Boc-Phe-Aha-OMe and Ac-Aha-Phe-OMe) [80]. Similarly, Cp2Mo2(CO)4 complexes of these alkynes were obtained. It has been shown that the C-terminal Met" in SP can be replaced by isostere analogs without appreciable loss of physiological activity. The same is true for the C-terminal Met in neurokinin A (NKA), another tachykinin peptide hormone (Scheme 5.16). Alkyne analogs of SP and NKA were obtained by replacement of these methionines with norleucine acetylene residues. Alternatively, Lys in NKA may be replaced by an alkyne derivative which can also be complexed to Co2(CO)g as shown in Scheme 5.16. Complexation with Co2(CO)g proceeds smoothly in about 50% yield for all derivatives [81]. After HPLC purification, these cobalt alkyne peptides were comprehensively characterized spectroscopically. Most notably, they exhibit typical IR absorptions for the metal carbonyl moieties between 2000-2100 cm [3]. Recently, there is renewed interest in Co2(CO)5(alkyne) complexes because of their cytotoxicity [82-84]. 

Yu, T.H. Ho, C.-T. 1995. Volatile compounds generated from thermal reaction of methionine and methionine sulfoxide with or without glucose. J. Agric. Food Chem. 1995, 43, 1641—1646. 

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