Leucine, and Isoleucine

BicoZamycin. Bico2amycin (bicyclomycin) [38129-37-2] C22H2gN20y, shown in Figure 6, is a colorless, water-soluble diketopipera2ine or cycHc dipeptide derived from leucine and isoleucine. It was simultaneously isolated in 1972 in Japan from cultures of two different strains (166). 

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. 

The nonpolar amino acids (Figure 4.3a) include all those with alkyl chain R groups (alanine, valine, leucine, and isoleucine), as well as proline (with its unusual cyclic structure), methionine (one of the two sulfur-containing amino acids), and two aromatic amino acids, phenylalanine and tryptophan. Tryptophan is sometimes considered a borderline member of this group because it can interact favorably with water via the N-H moiety of the indole ring. Proline, strictly speaking, is not an amino acid but rather an a-imino acid. 

Peptides inside the mass specttometet ate broken down into smaller units by coUisions with neuttal helium atoms (collision-induced dissociation), and the masses of the individual fragments are determined. Since peptide bonds are much more labile than carbon-carbon bonds, the most abundant fragments will differ from one another by units equivalent to one or two amino acids. Since—with the exception of leucine and isoleucine—the molecular mass of each amino acid is unique, the sequence of the peptide can be reconstructed from the masses of its fragments. 

Valine, Leucine, and Isoleucine. While leucine, valine, and isoleucine are all nutritionally essential... 

In some cases they may serve to differentiate between selected amino acids. In particular, they allow one to distinguish between leucine and isoleucine, which have identical molecular weights but yield different sateHite ions (Fig. 6.9). 

Figure 6.9. The analysis of satellite ions may help to differentiate between leucine and isoleucine, which have identical molecular weights and cannot be distinguished in most MS/ MS experiments. In high energy CID, Leu loses a 43 Da radical, while lie loses a 29 Da fragment.

R. S. Johnson, S. A. Martin, K. Biemann, J. T. Stults, and J. T. Watson, Novel Fragmentation Process of Peptides by Collision-Induced Decomposition in a Tandem Mass Spectrometer Differentiation of Leucine and Isoleucine. Anal. Chem., 59(1987) 2621-2625. 

Methionine metabolism Cysteine metabolism Valine, leucine, and isoleucine degradation... 

Valine, leucine, and isoleucine biosynthesis Lysine biosynthesis Lysine degradation Arginine and proline metabolism Histidine metabolism Tyrosine metabolism Phenylalanine metabolism Tryptophan metabolism Phenylalanine, tyrosine, and tryptophan biosynthesis Urea cycle and metabolism of amino groups... 

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). 

Johnson R.S., Martin S.A., Biemann K., Stulz J.T., and Watson J.T. (1987), Novel fragmentation process of peptides by collision-induced decomposition in a tandem mass spectrometer differentiation of leucine and isoleucine, Anal. Chem. 59, 2621-2625. 

Valine, leucine, and isoleucine are branched-chain amino adds whose metabolism is abnormal in maple syrup urine disease (discussed in Chapter 17). 

The aliphatic amino acids (class 1) include glycine, alanine, valine, leucine, and isoleucine. These amino acids do not contain heteroatoms (N, 0, or S) in their side chains and do not contain a ring system. Their side chains are markedly apolar. Together with threonine (see below), valine, leucine, and isoleucine form the group of branched-chain amino acids. The sulfurcontaining amino acids cysteine and methionine (class 11), are also apolar. However, in the case of cysteine, this only applies to the undissociated state. Due to its ability to form disulfide bonds, cysteine plays an important role in the stabilization of proteins (see p. 72). Two cysteine residues linked by a disulfide bridge are referred to as cystine (not shown). 

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). 

Of the various isomeric amino-caprok acids only leucine and isoleucine occur in the protein molecule both of them, combined with tyrosine and valine in the form of polypeptides, from which they are easily split off by enzymes, seem to form a very important part of most proteins. 

The nonpolar or hydrophobic amino acids—glycine, alanine, valine, leucine, and isoleucine-have alkyl side chains (or simply a hydrogen atom in the case of glycine). 

The commercially-available (S)-amino acids alanine, valine, leucine and isoleucine usually contained only negligible amounts (a few parts/thousand) of the (R)-antipode, but occasionally up to Z.5% of the (R)-enantiomer has been detected in (S)-alanine and (S)-valine. The (R)-enantiomer is almost completely removed by one recrystallization from water. 

Concentrated hydrochloric acid is diluted by its own volume with water. Hydrochloric acid (2.4 L, 5 N) is employed for the less soluble (S)-araino acids valine, leucine and isoleucine. 

Certain limitations for complete sequence information with tandem mass analysis do exist. In determining the amino acid sequence of a peptide, a complete ion series could be used except that neither leucine and isoleucine, nor lysine and glutamine can be differentiated because they have the same mass. As a complete ion series is not usually observed, the information from both the N- and C-terminal ions must be used to help determine the entire sequence. 

---