Compounds from reaction with methionine

FIGURE 7.27 Ester (IR 1825-1815 cm4) and amide IV-oxide (amide 3-oxide) (IR 1750-1730 cm4) forms of benzotriazole adducts.94 R = R O and R 0C(=0)-Xaa. Compounds with R = tBuO and PhCH2 are amide forms.97 The product from reaction of Trt-methionine and HOBt is the amide 3-oxide96 (Trt = trityl = triphenylmethyl). Note that the atoms bearing the oxygen atoms are numbered differently in the two compounds. 

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). 

Release of compound from the resin Resin bearing the methionine Hnker (0.9 g) was treated with a cyanogen bromide solution (4 mL 20 mg mL in 0.1 N HCl) at 25 °C for 12 h under exclusion of hght. The reaction was stopped by freezing and lyophilization. The crude product 105 was extracted with methanol. 

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... 

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. 

The demethylation reactions so far outlined take us to dimethylglycine. Nothing concrete is known on the further demethylation of this compound. Since N -betaine has been shown to be converted to labeled glycine the demethylation must go to completion. Similarly the role of sarcosine in the proposed cycle is obscure. In feeding experiments sarcosine was found not to be an effective methyl donor for choline formation. " This also was observed for the synthesis of methionine from homocysteine with liver slices and homogenates. The oxidation of the sarcosine methyl to formaldehyde, on the other hand, is a very active process and sarcosine oxidase is very widely distributed. This reaction could serve as a pathway for the catabolism of surplus methyl groups in the body. 

Putrescine, which is produced by decarboxylation of ornithine, and also arises from agmatine with catalysis by agmatinase, becomes the starting compound for the biosynthesis of spermidine and spermine. These reactions are catalysed by spermidine synthase and spermine synthase, respectively, involving S-adenosyl-L-methionine (for short AdoMet or SAM), and take place from bacteria to mammals (Figure 10.16). S-Adenosyl-L-methionine amide (dSAM) formed by decarboxylation of SAM provides trimethylene amine residue for this biosynthesis, which yields S-methyl-5 -thioadenosine (MTA). 

Incubations were set up as specified in Fig. 3, resulting in the consumption of more than 90 % of the substrates according to n. m. r. analysis of suitable model compounds the methionine produced was isolated by ion exchange technique and subsequently converted into its bis-trimethylsilyl (bis-TMS) derivatives upon reaction with N-(trimethylsilyl)diethylamine. Control experiments, in which the substrates, or homocysteine, were omitted from the incubations, gave no trace of methionine. A non-catalyzed methionine formation, detectable in the absence of the enzyme preparation, proceeded with a rate too low to seriously compete with the enzyme-catalyzed reaction. 

The structure of cobalamin is more complex than that of folic acid (Figure 15.2 and 15.3). At its heart is a porphyrin ring containing the metal ion cobalt at its centre. In catalytic reactions the cobalt ion forms a bond with the one-carbon group, which is then transferred from one compound to another. Vitamin B12 is the prosthetic group of only two enzymes, methylmalonyl-CoAmutase and methionine synthase. The latter enzyme is particularly important, as it is essential for the synthesis of nucleotides which indicates the importance of vitamin B12 in maintenance of good health. 

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