Amino 2-aminoadipic acid

Weber, P. L. Buck, D. R. Capillary Electrophoresis A Past and Simple Method for the Determination of the Amino Acid Composition of Proteins, /. Chem. Educ. 1994, 71, 609-612. This experiment describes a method for determining the amino acid composition of cyctochrome c and lysozyme. The proteins are hydrolyzed in acid, and an internal standard of a-aminoadipic acid is added. Derivatization with naphthalene-2,3-dicarboxaldehyde gives derivatives that absorb at 420 nm. Separation is by MEKC using a buffer solution of 50 mM SDS in 20 mM sodium borate. 

The first biosynthetic steps are two reactions that generate ACV from its constituent amino acids L-a-aminoadipic add, L-cysteine and L-valine. L-a-aminoadipic acid and L-cysteine are condensed by the enzyme AC synthetase and, in the next step, the resultant 8-(L-a-aminoadipyl)-L-cysteine is coupled with L-valine. In this step the configuration of L-valine is inverted to D-valine. 

Figure 6.9 Formation of isopenicillin N from its constituent amino acids. After condensation of L-a-aminoadipic acid with L-cysteine, L-valine is coupled. During this transformation, the configuration of the latter amino acid inverts to give D-valine.

The building blocks for the biosynthesis of benzylpenicillin are three amino acids, a-aminoadipic acid, cysteine and valine, and PAA. The amino acids condense to a tripeptide, ring closure of which gives the penicillin ring structure with an cu-aminoadipyl side-chain, isopenicillin N. The side-chain is then displayed by a phenylacetyl group from PAA to give benzylpenicillin. 

A simple example is the tripeptide precursor of the penicillin antibiotics, called ACV, an abbreviation for S-(L-a-aminoadipyl)-L-cysteinyl-D-valine. The amino acid precursors for ACV are L-a-aminoadipic acid (an unusual amino acid derived by modification of L-lysine), L-cysteine, and L-valine (not o-valine). 

The cephalosporins, discovered in the 1950s, are produced by various species of the mold Cephalosporium. Cephalosporin C (9.46) is the prototype of these antibiotics, and its structure shows a close similarity to the penam stmcture. The 5-thia-l-azabicyclo[4.2.0] octane ring system is therefore called the cepham ring. The parent compound carries the aminoadipate side chain, which can be cleaved to supply the 7-amino-cephalosporanic acid. This amine can easily be acylated and thus forms the basis of many useful derivatives. The 3-acetoxymethyl substiment is also amenable to modifications. 

The essential amino acid lysine (2,5-diaminohexanoic acid) can be degraded via two pathways, viz. the so-called saccharopine pathway and the pipecolic acid (PA) pathway. Both pathways merge at the level of a-aminoadipic acid semialdehyde (AASA). It is generally accepted that the saccharopine pathway constitutes the major breakdown pathway. However, the PA pathway has attracted much attention since the discovery of the association between the presence of elevated PA levels and Zellweger syndrome almost 40 years ago. Mainly because the analysis of amino acids was the primary biochemical approach for studying presumed inborn errors of metabolism, PA in Zellweger syndrome was discovered even before it was realized that this disorder was based on a defect of peroxisomal functions. 

The specifically 13C-enriched compounds were useful for the signal identification of the 13C NMR spectrum of this microbial product. Spectral comparison of cephalosporin C with a-aminoadipic acid-N-ethylamide, cephalexin, 3-methyl-7 (2-phenoxyacetamido)-3-cepham and 7-amino cephalosporanic acid led to the total signal identification of this antibiotic. The shifts are listed in Table 5.46. 

Fig. 5. Chromatogram of 24-hr urine specimen (sample 2/10 ml 360 ml/12 hr) in a case of hepatic coma in a 9-year-old child (D24). The following features are to be noted considerable increase in output of substances corresponding to all peaks presence of a-aminoadipic acid, a-amino-butyric acid (following the a-alanine peak), and tryptophan.

More specific and growing uses of microorganisms are in the areas of finding enzymes for specific tasks, especially if one can integrate with established biological transformations. Thus, the Antibioticos success in harnessing an amino acid oxidase to convert the aminoadipic acid side chain of cephalosporin C into a glutaroyl side... 

Benzoic acids substituted with alkyl, halo, hydroxyl, alkoxyl, cyano, or nitro groups react to give the corresponding substituted anilines in 41-80% yields. The carboxyl group in an a-amino acid does not react with hydrazoic acid the reaction proceeds, however, if the amino group is further removed. This difference in reactivity is shown by the conversion of a-aminoadipic acid to i(-ornithlne (75%). ... 

Fig. 10. Structures of nonribosomally synthesized peptides of bacterial origin (1-6) and fungal origin (7-9). Me, N-methylated peptide boni Orn, ornithine 4-MHA, 4-methyl-3-hydroxyanthranilic acid Aad, aminoadipic acid Aeo, 2-amino-9,10-epoxy-8-oxodecanoic acid D-Hiv, D-hydroxyisovaleric acid Bmt, (4i )-4-[( )-2-butenyl]-4-methyl-L-threonine Abu, a-aminoisobutyric acid Sar, sarcosine. The boxes signify gene products for peptide synthetases composed of modules which activate and process the indicated amino acids...

After the secretion into the extracellular space, collagen molecules may be modified chemically even more. Some collagen processing enzymes cleave the procollagen molecules to mature tissue type molecules. Lysine and 5-hydroxylysine residues can be modified enzymatically to allysine (alpha-aminoadipic-acid delta-semialdehyde) and hydroxyallysine (delta-hydroxy, alpha-aminoadipic acid delta-semialdehyde), respectively, by lysyl oxidase (protein-lysine 6-oxidase) (EC 1.4.3.13). The aldehyde group then interacts with the amino group of an adjacent lysine residue to form a Schiff base. Many... 

Equation 9.8 shows a simplified scheme of the biosynthesis of penicillin. It starts with the amino acids L-a-aminoadipic acid and L-cysteine from penicillin N in a complex reaction sequence. When phenyl acetic acid is added to the fermentation medium, the side chain of the molecule is modified and the resulting product is called penicillin G. Today, several hundred antibiotics are on the market, most of them have at least one fermentation step in the production process. The production of antibiotics is in the order of 50,000 t/year. 

Vigabatrin can produce an abnormal urinary amino acid pattern, which can be diagnostically confusing (SEDA-16, 74). It increases plasma and urinary alpha-aminoadipic acid concentrations, possibly comphcating the diagnosis of alpha-aminoadipicaciduria (SEDA-20, 71). 

Although cephalosporin C is divisable into a-aminoadipic acid, cysteine, and valine, the actual mechanism whereby Cephalosporium sp. incorporates the three amino acids into cephalosporin C has not been established, Arnstein and Morris isolated 8 (a-aminoadipyl) cysteinyl valine from mycelia of Penicillium chrysogenum and suggested that the tripeptide is a precursor in all penicillin biosynthesis.. This same tripeptide also appears to be found in the intracellular pool of Cephalosporium sp.- The final postulated step in the biosynthesis of penicillin is an acyl transfer reaction, or the production of 6-aminopeni-cillanic acid if precursor is not added. Cephalosporium sp. apparently do not produce sidechain amidases or acyl transferases, and no 7-ACA has been reported found in the fermentation. Thus, to obtain clinically useful antibiotics, chemical manipulation of cephalosporin C is necessary. Synthesis of many 7-acyl derivatives was possible once a practical cleavage reaction made available large amounts of 7-ACA from cephalosporin C. of these derivatives, sodium cephalothin was the first... 

L-a-amino-/3-phenylbutyric acid, a, /3-diaminobutyric acid L-a, jJ-diaminopropionic acid, / -aminopropionic acid d-aminovaleric acid, 2-aminohexenoic acid, 6-diazo-5-oxo-amino-hexanoic acid D-a-aminoadipic acid... 

Cephalosporins are derived from cepham. Cephalosporin C, a metabolite of Cephalosporium acremonium, was isolated by Newton and Abraham in 1955. Its structure was established in 1961 by chemical methods and X-ray diffraction. It is an acid amide derived from (i )-a-aminoadipic acid and 7-aminocephalosporic acid. The latter is (6i ,7i )-3-acetoxymethyl-7-amino-8-oxoceph-3-em-4-carboxylic acid. 

I. 1-1) starts with the polymerization of L-a-aminoadipic acid, L-cysteine, and L-valine to the linear tripeptide L-a-aminoadipyl-L-cysteinyl-D-valine(ACV-peptide). This reaction is catalyzed by the ACV-synthase (MW about 420 kD) through the following steps (1) the ATP-dependent activation of these amino acids to bind them as thiolesters, (2) the epimerization of L-valine, and hnally (3) the condensation by a thiotemplate mechanism [99]. 

Effect of Substrates on Penicillin Production. It is known that penicillin G is synthesized from three amino acids (L- -aminoadipic acid, L-cysteine, and L-valine) and the sidechain precursor, phenyl acetate. Furthermore, penicillin acyltrans-ferase, an enzyme presumably involved in the final step of penicillin G synthesis, catalyzes penicillin G synthesis from 6-aminopenicillanic acid (6-APA) and phenyl acetate. Therefore, the effect of these substrates on penicillin production by the immobilized mycelium was examined (Table II). Penicillin productivity by inmobilized mycelium in each substrate was expressed relative to that observed in glucose-(NH.)2S0, medium. As shown in Table II, the rate of penicillin produStTon in a... 

C11H20N2O6, Mr 276.29, mp. 240-248°C (decomp.), [a] 3 +33 go (0.5 m HCl), +8.1 ° (0.5 m NaOH), pK 2.6, 4.1,9.2, 10.3. A widely distributed non-proteinogenic amino acid in Saccharomyces cerevisiae, Candida utilis, Lentinus edodes, Agaricus bisporus, tobacco leaves (Nicotiana tabacum), and other plants. Metabolism S. is a direct precursor of lysine in the biosynthesis and the first product of lysine catabolism. The responsible enzyme is saccharopine dehydrogenase (EC 1.5.1.8). S. is degraded to 2-aminoadipic acid... 

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