Valine acid intermediates

Isoleucine and valine. The first four reactions in the degradation of isoleucine and valine are identical. Initially, both amino acids undergo transamination reactions to form a-keto-/T methyl valerate and a-ketoiso valerate, respectively. This is followed by the formation of CoA derivatives, and oxidative decarboxylation, oxidation, and dehydration reactions. The product of the isoleucine pathway is then hydrated, dehydrogenated, and cleaved to form acetyl-CoA and propionyl-CoA. In the valine degradative pathway the a-keto acid intermediate is converted into propionyl-CoA after a double bond is hydrated and CoA is removed by hydrolysis. After the formation of an aldehyde by the oxidation of the hydroxyl group, propionyl-CoA is produced as a new thioester is formed during an oxidative decarboxylation. 

For complete hydrolysis of bonds between hindered amino acid residues the above mentioned 16 hour period is not sufficient. In addition to isoleucine and valine synthetic intermediates can contain residues with bulky and acid resistant blocking groups, such as S-benzylcystein. Should the latter be preceded or followed by a hindered amino acid, then the time of hydrolysis must be considerably prolonged. Since the hydroxyamino acids and also tryptophan gradually decompose under these conditions, it might be necessary to carry out more than one analysis, with shorter and longer hydrolysis times. 

The production of oxoisovaleric acid and oxoisocaproic acids, intermediates in the biosynthesis of valine and leucine respectively, is shown in Fig. 17.16. The decarboxylation and reduction (NAD+ dependent) of these oxo-acids yields the fusel alcohols isobutanol and isoamyl alcohol (Fig. 17.16). Presumably, some oxo-acids in beer result from excretion from the pool and some aldehydes by excretion prior to reduction to the corresponding alcohol. Table 17.7 shows the chemical relationships between alcohols, aldehydes, oxo-acids and corresponding amino acids. 

The initial aims of this study were to test the full-length glycine-containing substrate with BaeJ KSl and examine the tolerance towards other amino acids. The glycine, alanine and valine derived a-keto acid intermediates 27-29 were... 

These acid intermediates of valine and isoleucine were the first to be isolated and identified from culture media of various mutants of Neurospora and E. cdi HI, HU, 168). The a, 8-dihydroxy acids were further characterized by their synthesis and by demonstrating the identity of the biological activity of the natural and synthetic compounds 14 ). 

Most of the naturally-occurring pyrazine hydroxamic acids appear to be derived from valine, leucine and isoleucine, and biosynthetic studies by MacDonald and coworkers (61JBC(236)512, 62JBC(237)1977, 65JBC(240)1692) indicate that these amino acids are incorporated. However, it would seem that the logical intermediates, viz. the 2,5-dioxopiperazines such as (111) and (112), are not always incorporated. This does not rule out their intermediacy, as there may be problems such as low solubility or membrane permeability which prevent their efficient incorporation. An exception to these results was reported for pulcherrimic acid (113) (65BJ(96)533), which has been shown to be derived from cyclo-L-leu-L-leu which serves as an efficient precursor. 

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. 

Methylmalonyl CoA mutase, leucine aminomutase, and methionine synthase (Figure 45-14) are vitamin Bj2-dependent enzymes. Methylmalonyl CoA is formed as an intermediate in the catabolism of valine and by the carboxylation of propionyl CoA arising in the catabolism of isoleucine, cholesterol, and, rarely, fatty acids with an odd number of carbon atoms—or directly from propionate, a major product of microbial fer-... 

Elimination reactions (Figure 5.7) often result in the formation of carbon-carbon double bonds, isomerizations involve intramolecular shifts of hydrogen atoms to change the position of a double bond, as in the aldose-ketose isomerization involving an enediolate anion intermediate, while rearrangements break and reform carbon-carbon bonds, as illustrated for the side-chain displacement involved in the biosynthesis of the branched chain amino acids valine and isoleucine. Finally, we have reactions that involve generation of resonance-stabilized nucleophilic carbanions (enolate anions), followed by their addition to an electrophilic carbon (such as the carbonyl carbon atoms... 

FIGURE 1.18 2-AI koxy-5(4/7)-oxazol ones as intermediates in reactions of IV-alkoxycarbo-nylamino acids.22 After removal of the symmetrical anhydride from a reaction mixture containing Boc-valine and ethyl-(3-dimethylaminopropyl)-carbodiimide hydrochloride, the filtrate contained a novel activated form of Boc-valine (20% yield) that was established to be the 2-alkoxy-5(4H)-oxazolone. Slow addition of Boc-valine to ethyl-(3-dimethylamino-propyl)-carbodiimide hydrochloride in dilute solution gave a 55% yield. Petrol = petroleum ether, bp 40-60°. 

During ACV formation, the stereochemistry of the valine component is changed. ACV is the linear tripeptide that leads to isopenicillin N, the first intermediate with the fused ring system found in the penicillins. Note, we are using the d and l convention for amino acid stereochemistry rather than the fully systematic R and S (see Section 3.4.10). This is one occasion where use of d and l is advantageous, in that the sulfur atom in L-cysteine means this compound has the R configuration, whereas the other L-amino acids have the S configuration. 

Figure 9-4. Metabolism of the branched-chain amino acids. The first two reactions, transamination and oxidative decarboxylation, are catalyzed by the same enzyme in all cases. Details are provided only for isoleucine. Further metabolism of isoleucine and valine follows a common pathway to propionyl CoA. Subsequent steps in the leucine degradative pathway diverge to yield acetoacetate. An intermediate in the pathway is 3-hydroxy-3-methylglutaryl CoA (HMG-CoA), which is a precursor for cytosolic cholesterol biosynthesis.

The radical intermediates and their yields are presented in Table III. It is noticeable that the G-values for production of a-carbon radicals are remarkably similar for the amino acids glycine, alanine, valine and glutamic acid, and are considerably higher than those for phenylalanine and tyrosine, indicative of the protective effect of the aromatic side chains. 

The carbon skeletons of methionine, isoleucine, threonine, and valine are degraded by pathways that yield suc-cinyl-CoA (Fig. 18-27), an intermediate of the citric acid cycle. Methionine donates its methyl group to one of several possible acceptors through S-adenosytmethionine,... 

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