Isoleucine reactions

Adenosylcobalamin (coenzyme B 2) is required in a number of rearrangement reactions that occurring in humans is the methylmalonyl-Co A mutase-mediated conversion of (R)-methylmalonyl-Co A (6) to succinjl-CoA (7) (eq. 1). The mechanism of this reaction is poorly understood, although probably free radical in nature (29). The reaction is involved in the cataboHsm of valine and isoleucine. In bacterial systems, adenosylcobalamin drives many 1,2-migrations of the type exemplified by equation 1 (30). 

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. 

In the desulfurization of 3-substituted thiophenes several stereoisomers may be formed in certain cases. Both meso and racemic compounds have been obtained from the desulfurization of 3,4-diaryl-substituted thiophenes. It is claimed, however, that only meso, -diphenyladipic acid is obtained upon desulfurization of 3,4-di-phenyl-2,5-thiophenedicarboxylic acid and only di-isoleucin from 3-thienylglycine. The formation of small amounts of dimeric products in the desulfurization has been discussed with reference to the mechanism of this reaction. ... 

Amino acids are metabolized by a transamination reaction in which the —NH2 group of the amino acid changes places with the keto group of an a-keto acid. The products are a new amino acid and a new a-keto acid. Show the product from transamination of isoleucine. 

As the name implies, the odor of urine in maple syrup urine disease (brancbed-chain ketonuria) suggests maple symp or burnt sugar. The biochemical defect involves the a-keto acid decarboxylase complex (reaction 2, Figure 30-19). Plasma and urinary levels of leucine, isoleucine, valine, a-keto acids, and a-hydroxy acids (reduced a-keto acids) are elevated. The mechanism of toxicity is unknown. Early diagnosis, especially prior to 1 week of age, employs enzymatic analysis. Prompt replacement of dietary protein by an amino acid mixture that lacks leucine, isoleucine, and valine averts brain damage and early mortality. 

Figure 30-19. The analogous first three reactions in the catabolism of leucine, valine, and isoleucine. Note also the analogy of reactions and to reactions of the catabolism of fatty acids (see Figure 22-3). The analogy to fatty acid catabolism continues, as shown in subsequent figures.

C13-0046. Draw the structures of all possible products resulting from condensation reactions between aspartic acid and isoleucine ... 

Model systems indicate that aldehydes may also be produced by the action of polyphenoloxidases on amino acids in the presence of catechin, all of which are present in coffee beans at some stage between green and roasted. For example, valine yields isobutanal, leucine yields isopentanal, and isoleucine yields 2-methyl-butanal.14 Some of these aldehydes probably undergo condensation reactions in the acidic medium of the roasted bean when moisture is present.15 Some dienals in green coffee beans have recently been identified as (E,E)-2,4- and (E,Z)-2,4-nonadienal and (E,E)-2,4- and (E,Z)-2,4-decadienal.18... 

It has been confirmed that isoleucine but not 3-hydroxy-2-methylbutanoic acid is a precursor for the tiglic acid which is the esterifying acid in some tropane alkaloids [e.g., meteloidine (77) (735)]. In the biosynthesis of meteloidine (77) from 3a-hydroxytropane (1), the hydroxyl groups at C-6 and C-7 are most probably introduced after esterification at C-3 (5) (Scheme 23). In this connection we would point out that scopolamine (89) is a well-known 2,3) metabolite of hyoscyamine (27) and that the reaction proceeds via 6-hydroxyhyoscyamine [(—)-anisodamine (63)] and 6,7-dehydrohyoscyamine (211) (Scheme 26). 

In mammals and in the majority of bacteria, cobalamin regulates DNA synthesis indirectly through its effect on a step in folate metabolism, catalyzing the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate via two methyl transfer reactions. This cytoplasmic reaction is catalyzed by methionine synthase (5-methyltetrahydrofolate-homocysteine methyl-transferase), which requires methyl cobalamin (MeCbl) (253), one of the two known coenzyme forms of the complex, as its cofactor. 5 -Deoxyadenosyl cobalamin (AdoCbl) (254), the other coenzyme form of cobalamin, occurs within mitochondria. This compound is a cofactor for the enzyme methylmalonyl-CoA mutase, which is responsible for the conversion of T-methylmalonyl CoA to succinyl CoA. This reaction is involved in the metabolism of odd chain fatty acids via propionic acid, as well as amino acids isoleucine, methionine, threonine, and valine. 

The complexity of the HCN oligomerisation reaction was also studied by Schwartz et al. (1984) in Nijmegen. The reactions worked best at a pH value which lies near the pK value of HCN. A list of the products of oligomerisation includes 38 compounds, including orotic acid, adenine, guanine and glycine, as well as more complex molecules such as isoleucine, glutamic acid, diaminosuccinic acid and... 

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... 

One of the most distinguishing features of metabolic networks is that the flux through a biochemical reaction is controlled and regulated by a number of effectors other than its substrates and products. For example, as already discovered in the mid-1950s, the first enzyme in the pathway of isoleucine biosynthesis (threonine dehydratase) in E. coli is strongly inhibited by its end product, despite isoleucine having little structural resemblance to the substrate or product of the reaction [140,166,167]. Since then, a vast number of related... 

The iminium salt 132, generated from benzylamine hydrochloride and aqueous formaldehyde, reacts with cyclopentadiene during 3 h at room temperature to give, after basification, the cycloadduct 133 in nearly quantitative yield (equation 70). Other examples of this reaction are shown in equations 71-75. The separable diastereomers 134 and 135 are formed in the ratio 4 1 from cyclopentadiene, (—)-a-methylbenzylamine hydrochloride and aqueous formaldehyde in a combined yield of 86% (equation 75)62. Hydrochlorides 136 of methyl esters of natural amino acids [(S )-valine, (S )-isoleucine] react with cyclopentadiene and formaldehyde in aqueous THF to produce mixtures of the diastereomers 137 and 138, in which the former predominate (equation 76)63. 

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). 

Similarly, chemical hydrolysis of a number of a-amino acyl prodrugs of metronidazole (8.100, R=H see Sect. 8.5.4) was compared to the serum-catalyzed reaction [135][136]. The amino acids used for esterification included alanine, glycine, isoleucine, leucine, lysine, phenylalanine, and valine. Under physiological conditions of pH and temperature, ty2 values for hydrolysis in human serum ranged from 4.5 min for the Phe ester to 96 h for the lie ester. A good linear relationship was established between the log of the rate constant of enzymatic hydrolysis and the log of the rate constant of HO-cata-... 

Another way to increase the host cavity is by using exchange reactions in y-CD (diameter of the cavity from 7.5 to 8.3 A) instead of j8-CD (diameter of the cavity from 6.0 to 6.5 A)." " The larger cavity size of y-CD decreases (and inverts) the enantioselectivity of valine from krJkL = 0.32 to kolk = 1.41 and that of isoleucine from ko/k = 0.26 to k /kL = 2.28. This observation indicates that the three amino acids have optimal enantioselectivity with j8-CD. Conversely, phenylalanine increases in selectivity from k /kL =1.2 (with j8-CD) to kolk =1.8 (with y-CD). This observation suggests that the larger cavity of y-CD allows each enantiomer of the larger amino acid to find more distinct interactions with the larger host. 

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