Valine, oxidation

Fatty acids with odd numbers of carbon atoms are rare in mammals, but fairly common in plants and marine organisms. Humans and animals whose diets include these food sources metabolize odd-carbon fatty acids via the /3-oxida-tion pathway. The final product of /3-oxidation in this case is the 3-carbon pro-pionyl-CoA instead of acetyl-CoA. Three specialized enzymes then carry out the reactions that convert propionyl-CoA to succinyl-CoA, a TCA cycle intermediate. (Because propionyl-CoA is a degradation product of methionine, valine, and isoleucine, this sequence of reactions is also important in amino acid catabolism, as we shall see in Chapter 26.) The pathway involves an initial carboxylation at the a-carbon of propionyl-CoA to produce D-methylmalonyl-CoA (Figure 24.19). The reaction is catalyzed by a biotin-dependent enzyme, propionyl-CoA carboxylase. The mechanism involves ATP-driven carboxylation of biotin at Nj, followed by nucleophilic attack by the a-carbanion of propi-onyl-CoA in a stereo-specific manner. 

Komori and Nonaka132,133 electrochemically oxidized methyl, isopropyl, n-butyl, isobutyl, r-butyl and cyclohexyl phenyl sulfides (108) and cyclohexyl p-tolyl sulfide (109) to their sulfoxides using a variety of polyamino acid-coated electrodes to obtain the range of e.e. values shown in parentheses. The highest enantiomeric purities were obtained using an electrode doubly coated with polypyrrole and poly(L-valine), an electrode which also proved the most durable of those prepared. 

Very low asymmetric induction (e.e. 0.3-2.5%) was noted when unsymmetrical sulphides were electrochemically oxidized on an anode modified by treatment with (— )camphoric anhydride or (S)-phenylalanine methyl ester299. Much better results were obtained with the poly(L-valine) coated platinum electrodes300. For example, t-butyl phenyl sulphide was converted to the corresponding sulphoxide with e.e. as high as 93%, when electrode coated with polypyrrole and poly(L-valine) was used. 

Several alkyl aryl sulfides were electrochemically oxidized into the corresponding chiral sulfoxides using poly(amino acid)-coated electrodes448. Although the levels of enan-tioselection were quite variable, the best result involved t-butyl phenyl sulfoxide which was formed in 93% e.e. on a platinum electrode doubly coated with polypyrrole and poly(L-valine). Cyclodextrin-mediated m-chloroperbenzoic acid oxidation of sulfides proceeds with modest enantioselectivity44b. 

Subsequently, a number of reactions at poly-L-valine coated carbon electrodes 237-243) gj.g reported to yield optically active products. Reductions, e.g. of citraconic acid or l,l-dibromo-2,2-diphenylcyclopropane as well as the oxidation of aryl-alkyl sulfides proceeded with chiral induction at such electrodes... 

In a muscle at rest, most of the 2-oxo acids produced from transamination of branched chain amino acids are transported to the liver and become subject to oxidation in reactions catalysed by branched-chain 2-oxo acid dehydrogenase complex. During periods of exercise, however, the skeletal muscle itself is able to utilize the oxo-acids by conversion into either acetyl-CoA (leucine and isoleucine) or succinyl-CoA (valine and isoleucine). 

K. Yeowell O Connell, W. Pauwels, M. Seven, Z. L. Jin, M. R. Walker, S. M. Rappa-port, H. Veulemans, Comparison of Styrene-7,8-oxide Adducts Formed via Reaction with Cysteine, N-Terminal Valine and Carboxylic Acid Residues in Human, Mouse and Rat Hemoglobin , Chem.-Biol. Interact. 1997, 106, 67 - 85. 

In an enantiomer-differentiating oxidation at a poly-(L-valine)-coated Pb02 anode, rac-2,2-dimethyl-l -phenyl-1 -propanol was partially oxidized leaving 43% optically pure (5)-alcohol [371]. At a TEMPO-modified graphite felt anode rac-1-phenyl-ethanol has been enantioselectively oxidized in the presence of (-[-sparteine leaving 46% of the (/ [-alcohol with 99.6% ee [372]. However, under the same conditions, an exclusive dehydrogenation of (-[-sparteine to the iminium salt without oxidation of the alcohol was found [373]. 

Catalases have proven to be a treasure trove of unusual modifications. The first noted modification was the oxidation of Met53 of PMC to a methionine sulfone (77). Met53 is situated in the distal side active site adjacent to the essential His54 in a location where oxidation by a molecule of peroxide would not be unexpected. Among the catalases whose structures have been solved, PMC is unique in having the sulfone because valine is the more common replacement in other catalases. The sulfone does not seem to have a role in the catalytic mechanism and is clearly generated as a posttranslational modification. A small number of catalases from other sources, principally bacteria, have Met in the same location as PMC, and it is a reasonable prediction that the same oxidation occurs in those enzymes as well, although this has not been demonstrated. 

The intermediary metabolism has multienzyme complexes which, in a complex reaction, catalyze the oxidative decarboxylation of 2-oxoacids and the transfer to coenzyme A of the acyl residue produced. NAD" acts as the electron acceptor. In addition, thiamine diphosphate, lipoamide, and FAD are also involved in the reaction. The oxoacid dehydrogenases include a) the pyruvate dehydrogenase complex (PDH, pyruvate acetyl CoA), b) the 2-oxoglutarate dehydrogenase complex of the tricarboxylic acid cycle (ODH, 2-oxoglutarate succinyl CoA), and c) the branched chain dehydrogenase complex, which is involved in the catabolism of valine, leucine, and isoleucine (see p. 414). 

Kuwata, K. T Valin, L. C. Converse, A. D. Quantum Chemical and Master Equation Studies of the Methyl Vinyl Carbonyl Oxides Formed in Isoprene Ozonolysis. J. Phys. Chem. A 2003, 109, 10710-10725. 

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