Aromatic amino acid utilization

See also Phenylalanine Hydroxylase, Aromatic Amino Acid Utilization,... 

See also Aromatic Amino Acid Utilization, Neurotransmitters and Biological Regulators, Biochemistry of Neurotransmission, Neurotransmitters and Receptors, Action of Epinephrine... 

The organism utilized is a mutant of E. coli blocked in the synthesis of aromatic amino acids before the shikimate step. Cells are first grown in the presence of adenosine, a technique that temporarily derepresses the system of en-... 

The major substrates for amino acid conjugation are benzoic acid and related aromatic carboxylic acids such as phenylacetic acid, phenoxyacetic acid, cinnamic acid, etc. (21). In humans, the major amino acid utilized in the conjugation is glycine however, glutamine and taurine can also be cofactors. In birds, the major amino acid utilized is ornithine. 

The oxidation state of thiazolines and oxazolines can be adjusted by additional tailoring enzymes. For instance, oxidation domains (Ox) composed of approximately 250 amino acids utilize the cofactor FMN (flavin mononucleotide) to form aromatic oxazoles and thiazoles from oxazolines and thiazolines, respectively. Such domains are likely utilized in the biosynthesis of the disorazoles, " diazonimides, bleomycin, and epothiolone. The typical domain organization for a synthetase containing an oxidation domain is Cy-A-PCP-Ox however, in myxothiazol biosynthesis one oxidation domain is incorporated into an A domain. Alternatively, NRPSs can utilize NAD(P)H reductase domains to convert thiazolines and oxazolines into thiazolidines and oxazolidines, respectively. For instance, PchC is a reductase domain from the pyochelin biosynthetic pathway that acts in trans to reduce a thiazolyinyl-Y-PCP-bound intermediate to the corresponding thiazolidynyl-Y-PCP. ... 

An intriguing puzzle in NOS catalysis is the precise role of H4B. The traditional function of H4B is in aromatic amino acid metabolism where H4B directly participates in the hydroxylation reaction via a nonheme iron. However, the NOS pterin site has no similarity to the pterin site in the hydroxylases, nor does NOS have a nonheme iron to assist pterin in substrate hydroxylation as in the amino acid hydroxylases 111). NOS more closely resembles pterin-containing enz5unes that have a redox function 81). In particular, N3 and the 03 amino group form H-bonds with either GIu or Asp residues in a series of pterin enzymes 112-116) similar to NOS, except that NOS utilizes the heme propionate (Fig. 6). 

Among the numerous enzymes that utilize pyridoxal phosphate (PLP) as cofactor, the amino acid racemases, amino acid decarboxylases (e.g., aromatic amino acids, ornithine, glutamic acid), aminotransferases (y-aminobutyrate transaminase), and a-oxamine synthases, have been the main targets in the search for fluorinated mechanism-based inhibitors. Pharmaceutical companies have played a very active role in this promising research (control of the metabolism of amino acids and neuroamines is very important at the physiological level). 

The helix contents of five peptide fragments from the protein thermolysin have been determined by CD and NMR in both water and 30% TFE. 85 The helix content was obtained from CD by the method of Chen et a I.162 and the NMR method utilized chemical shifts. 84 Four of the five peptides correspond to helical regions in the intact protein, and one corresponds to an Q-loop. 86 The rms difference between CD and NMR helix contents for the five peptides under the two conditions is 7.5%. One peptide shows the largest deviations (0 vs 13% in water, 45 vs 62% in 30% TFE). If it is excluded, the rms deviation decreases to 4%. The peptide showing the largest deviation, residues 258-276 from the thermolysin sequence, has two Tyr and one Phe (with the Phe adjacent to one of the Tyr in the sequence), and therefore it has an above-average content of aromatic amino acids, which can perturb both the CD spectrum and NMR chemical shifts. Of the other four peptides, three have a single aromatic residue and the fourth has two aromatics. 

Studies with the macrophage NOS were the first to show that NO synthesis was partially dependent on added Hbiopterin (Kwon et ai, 1989 Stuehr et al., 1990), which is a redox active cofactor utilized by the aromatic amino acid hydroxylases (Nichol et al., 1985). The requirement for H4biopterin has since been expanded to include all NOS isoforms studied to date. Mayer et al. (1990)... 

Aromatic compounds arise in several ways. The major mute utilized by autotrophic organisms for synthesis of the aromatic amino acids, quinones, and tocopherols is the shikimate pathway. As outlined here, it starts with the glycolysis intermediate phosphoenolpyruvate (PEP) and erythrose 4-phosphate, a metabolite from the pentose phosphate pathway. Phenylalanine, tyrosine, and tryptophan are not only used for protein synthesis but are converted into a broad range of hormones, chromophores, alkaloids, and structural materials. In plants phenylalanine is deaminated to cinnamate which yields hundreds of secondary products. In another pathway ribose 5-phosphate is converted to pyrimidine and purine nucleotides and also to flavins, folates, molybdopterin, and many other pterin derivatives. 

Numerous other amino acid decarboxylases have been isolated and characterized, and much interest has been shown as a result of the irreversible nature of the reaction with the release of C02 as the thermodynamic driving force. Although these enzymes have narrow substrate-specificity profiles, their utility has been widely demonstrated. Additional industrial processes will continue to be developed once other decarboxylases become available. Such biocatalysts would include the aromatic amino acid (E.C. 4.1.1.28), phenylalanine (E.C. 4.1.1.53) and tyrosine (E.C. 4.1.1.25) decarboxylases, which likely could be used to produce derivatives of their respective substrates. These derivatives are finding increased use in the development of peptidomimetic drugs and as possible positron emission tomography imaging agents.267-268... 

The utilization of evolutionary strategies in the laboratory can be illustrated with proteins that catalyze simple metabolic reactions. One of the simplest such reactions is the conversion of chorismate to prephenate (Fig. 3.3), a [3,3]-sigmatropic rearrangement. This transformation is a key step in the shikimate pathway leading to aromatic amino acids in plants and lower organisms [28, 29]. It is accelerated more than a million-fold by enzymes called chorismate mutases [30],... 

The shikimate pathway is utilized by plants to form aromatic amino acids.107 109 In this bioprocess, shown in Scheme 1.4.8, D-erythrose-4-phosphate is combined with phosphophenylpyruvate giving 3-deoxy-D-arabino-heptulosonic acid-7-phosphate (DAHP). The next step utilizes DHQ synthase to convert DAHP to dehydroquinate (DHQ). 

Soil is extremely rich in bacteria (10 —10 cells per g soil), which survive by utilizing nutrients and carbon sources present there. Naturally occurring aromatic compounds are present in soil from the breakdown of lignin from woody plants and phenylpropanoids found in plants the aromatic fraction of leached oil and coal as well as the aromatic amino acids L-phenylalanine, L-tyrosine, and L-tryptophan from protein breakdown (Figure 1). Man-made aromatic compounds include pesticides, detergents, oils, solvents, paints, and explosives. 

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