Isoleucine Isomers

The asterisk signifies an asymmetric carbon. AH of the amino acids, except glycine, have two optically active isomers designated D- or L-. Isoleucine and threonine also have centers of asymmetry at their P-carbon atoms (1,10). Protein amino acids are of the L-a-form (1,10) as illustrated in Table 1. 

FIGURE 4.14 The stereoisomers of isoleucine and threonine. The structures at the far left are the naturally occurring isomers. 

The molecules of two organic compounds are sometimes composed of the same type and number of atoms, but arranged in different ways. The molecular formula of each one of such compounds, which are known as isomers (for example, isoleucine and alloisoleucine, shown in Fig. 73), is therefore identical to that of the other only the structural formulas of the two isomers show the differences between their molecules (see Textbox 63). 

L and the D/L ratio approaches zero. After the death of the living organism, proteins start to spontaneously break down. An inter-conversion of the amino acids occurs from one chiral form (L) to a mixture of D- and L- forms following protein degradation this process is called amino acid racemisation. The extent of racemisation is measured by the ratio of D/L isomers and increases as a function of time and temperature. The longer the racemisation process continues the closer to 1 the ratio between the D- and L-forms becomes. If the D/L ratio is <1 it may be possible to use it to estimate age. The D/L ratio of aspartic acid and isoleucine are the most widely used for this dating technique [104]. Dates have been obtained as old as 200 000 years. However, it has been used mainly to date samples in the 5000 100 000 year range. Recent studies [ 105] mention an estimation of the method accuracy to be around 20%. 

Isoleucine is a constitutional isomer of leucine. Note that isoleucine has two chiral centers. 

Similarly, D-isoleucine is sweet but L-isoleucine is bitter. Both D-leucine and d-valine are sweet but their l isomers are tasteless to bitter. 

Diastereoisomers. Whereas compounds with one chiral center exist as an enantiomorphic pair, molecules with two or more chiral centers also exist as diastereoisomers (diastereomers). These are pairs of isomers with an opposite configuration at one or more of the chiral centers, but which are not complete mirror images of each other. An example is L-threonine which has the 2S, 3R configuration. The diastereoisomer with the 2S, 3S configuration is known as i-a//o-threonine. L-isoleucine, whose side chain is -CH(CH3) CH2CH3, has the 2S, 3R configuration. It can be called 2(S)-amino-3(R)-methyl-valeric acid but the simpler name L-isoleucine implies the correct configuration at both chiral centers. 

The two epimeric 7-turn mimetics 162 and 163 were synthesized from the respective isomer of leucine 154 and 155 (Scheme 34). The two chiral reagents 156 and 159 were synthesized from (.S )-HOC isoleucine and (/5-lcucinc. respectively <1997TL6961>. 

On the other hand, if the L-isomers 134 are mixed with the tolylurea 133a, 100% heterodimerization is observed for the (3-branched amino acid derivatives 134c,d (derived from isoleucine and valine) in benzene-d6. This preference for the heterodimerization is less pronounced for the other amino acid derivatives and also in the more polar CDC13 as a solvent (which is also known to be a less favorable guest). Moreover, only one of the two diastereomeric heterodimers LAP-BM or LAM-BP is observed in the case of 134c and 134d, and again this diastereoselectivity is less pronounced for the other examples. 

This enzyme s role in humans is to assist the detoxification of propionate derived from the degradation of the amino acids methionine, threonine, valine, and isoleucine. Propionyl-CoA is carboxylated to (5 )-methylmalonyl-CoA, which is epimerized to the (i )-isomer. Coenzyme Bi2-dependent methylmalonyl-CoA mutase isomerizes the latter to succinyl-CoA (Fig. 2), which enters the Krebs cycle. Methylmalonyl-CoA mutase was the first coenzyme B -dependent enzyme to be characterized crystallographically (by Philip Evans and Peter Leadlay). A mechanism for the catalytic reaction based on ab initio molecular orbital calculations invoked a partial protonation of the oxygen atom of the substrate thioester carbonyl group that facilitated formation of an oxycyclopropyl intermediate, which connects the substrate-derived and product-related radicals (14). The partial protonation was supposed to be provided by the hydrogen bonding of this carbonyl to His 244, which was inferred from the crystal structure of the protein. The ability of the substrate and product radicals to interconvert even in the absence of the enzyme was demonstrated by model studies (15). 

Contrasting isomers. Poly-l-leucine in an organic solvent such as dioxane is a helical, whereas poly-l-isoleucine is not. Why do these amino acids with the same number and kinds of atoms have different helix-forming tendencies ... 

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