Y -Elimination reactions

This pyridoxal-phosphate-dependent enzyme [EC 4.2.99.9], also known as cystathionine y-synthase, catalyzes the reaction of O-succinyl-L-homoserine with L-cysteine to produce cystathionine and succinate. The enzyme can also use hydrogen sulfide and methanethiol as substrates, producing homocysteine and methionine, respectively. In the absence of a thiol, the enzyme can also catalyze a /3,y-elimination reaction to form 2-oxobu-tanoate, succinate, and ammonia. 

The observation of this y-elimination reaction has raised the question, whether in DNA the related C(l ) radical can also lead to strand breakage. However due to the negative charge at the phosphate group in 3 -position, the rate of the y-elimi-nation reaction (54) should be considerably slower than that of reaction (53). 

Elimination reactions are typically found in transition metal chemistry. The conversion of allylic ethers into allylzirconocenes [18] is a well-known zirconium-mediated process of this type. In contrast, the y-elimination reactions are less frequently encountered, and only a few examples of y-elimination involving zirconocenes have been reported. When studying isonitrile insertion into zirconacycles, Whitby and coworkers observed an interesting reaction leading to a cyclopropane derivative [19]. The overall transformation is depicted in Scheme 12. Treatment of the diene 18 with preformed butene-zirconocene gave... 

Table 5-6. Predicted solvent effects on rates of y -elimination reactions [16, 44, 73, 74].

Decarboxylation reactions provide another route to the formation of a carbanion, thereby initiating this way the y-elimination reaction (equation 25). In the absence of an... 

An example of a y-elimination reaction is the formation of a cyclopropane from 1-pyrazoline initiated either by heat or light. The initial biradical, which is formed by the loss of the nitrogen molecule, then closes the ring to give the cyclic product. The conversion of R-CO-R to R-R and C=0 is called a Norrish Type I reaction. In this case, the C C bonds on each side of the carbonyl group cleave, and the resultant radicals then combine and so effect the extrusion of the CO molecule. 

A further PLP reaction involving enamine chemistry has to do with j ,y-elimination reactions, that probably commences analogously to the well-characterized transamination reaction. Instead of hydrolysis of the Schiff base, these reactions result in proton abstraction, this time at the rather than the a carbon of the amino acid. The intermediate iminium ion is the electron sink that helps to acidify the )3 proton (equation... 

Cystathionine y-synthase (CGS) is a rather unique PLP-enzyme that catalyzes a transsulfuration reaction important in microbial methionine biosynthesis. It is the only known enzyme whose function is the catalysis of a PLP-dependent replacement reaction at the y-carbon of the amino acid substrate the succinyl moiety of O-succinyl-L-homoserine is replaced by i-Cys to give the thioether linkage of L,/.-cystathionine (scheme II). In the absence of L-Cys, the enzyme catalyzes a net y-elimination reaction from OSHS (scheme II). Because both reactions require the elimination of succinate, the catalytic pathways must diverge from a common reaction intermediate. It was originally hypothesized that a vinylglycine quinonoidal intermediate (structure 11)... 

Fig. 20. Rapid-scanning, stopped-flow spectra (A), difference spectra (B), and singlewavelength, stopped-flow time courses at 300, 422, and 485 nm (C, D, E) for the y-elimination reaction of CGS with OSH S. Data were obtained as described in Figure 19. All concentrations refer to conditions immediately after mixing [OSHS] = lOmM, [CGS] = 6.25 pM, 0.1 M potassium phosphate, 1 mM EDTA, pH 7.2 at 25°C. (A) RSSF spectra, Trace 0 is the spectrum of the enzyme in the absence of substrates. The initiation of scanning occurred 1.3 ms after flow stopped. Spectra shown were collected at 1.3,10.2, 19.1, 28.0, 36.9, 72.5, 117.0, 161.5, 250.5, 392.9, and 695.5 ms after flow stopped. (B) Difference spectra were computed as (scan)t-(scan)0 from the data presented in (A). Singlewavelength time courses (C-E) were collected in SWSF experiments under conditions identical with those described for (A). [Taken from Brzovic et al. (107) with permission.]...

Cystathionine y-synthase is the best studied enzyme catalyzing both y-replacement and /3,y-elimination reactions. The enzyme is found in plants and bacteria and normally functions to catalyze the formation of cystathionine from 0-acylhomoserine and cysteine during the biosynthesis of methionine (66) [Eq. (57)] ... 

The enzyme also catalyzes a /3,y-elimination reaction with homoserine (in the absence of cysteine) to form a-ketobutyrate, a reaction having no apparent physiological significance. The results of various isotope-labeling studies on both the normal substitution and aberrant elimination reactions have given rise to a reasonably clear picture of the stereochemical features of this interesting reaction. Experiments on the enzyme from Salmonella by Flavin and co-workers, as well as others, demonstrated that the /8,y-elimination reaction involves significant... 

PLP can catalyze both a,j8-elimination reactions (Problem 31) and 8, y-elimination reactions. Propose a mechanism for the following PLP-catalyzed j8, y-elimination ... 

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