Amino acids Phenylalanine Phe

Figure 9-3. Fates of the carbon skeletons upon metabolism of the amino acids. Points of entry at various steps of the tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis are shown for the carbons skeletons of the amino acids. Note the multiple fates of the glucogenic amino acids glycine (Gly), serine (Ser), and threonine (Thr) as well as the combined glucogenic and ketogenic amino acids phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). Ala, alanine Cys, cysteine lie, isoleucine Leu, leucine Lys, lysine Asn, asparagine Asp, aspartate Arg, arginine His, histidine Glu, glutamate Gin, glutamine Pro, proline Val, valine Met, methionine.

The main features of the near- and far-ultraviolet spectra of the proteins are related to the absorption properties of the aromatic amino acids phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), and histidine (His) [113,114]. The peaks observed in the absorption spectra up to 185 nm (6.70 eV) can be assigned to the excited states of the chromo-phore-acting molecules benzene, phenol, indole, and imidazole, respectively. In the present section we focus on the theoretical description of the most representative valence singlet excited states of the aromatic amino acid chromophores. As the results for benzene and phenol have been recently described [13, 46], only the results for indole, [(4) in Fig. 3] and imidazole [(5) in Fig. 3] are reviewed here [115,116]. The theoretical results support the assignment of four valence singlet states as... 

As shown in Scheme 11.84, chorismate yields prephenate. As will be seen here, vide infra, prephenate can yield both phenylpyruvate and p-hydroxyphenylpyruvate. Although these phenylpropanoids can simply cyclize to the corresponding lactones, reductions to the respective alcohols and subsequent dehydrations lead to the respective cinnamates. Amino acids (phenylalanine [Phe, F] and tyrosine [Tyr, Y]) result from the transamination (respectively) of these ketoacids. 

It is important at this point to digress because the amino acid phenylalanine (Phe, F) is the progenitor of a vast class of nonnitrogenous plant products the phenylpropanoids. 

Phenylalanine (Phe, F) is most conveniently synthesized by the azlactone (oxa-zolone) method. Thus, when hippuric acid (A -benzoylglycine) is heated with benz-aldehyde in the presence of anhydous sodium acetate (Na02CCH3) in glacial acetic acid (CH3CO2H), the corresponding azlactone (oxazolone) is obtained. Treatment of the latter with cold HI and red phosphorus followed by hot water produces the amino acid phenylalanine (Phe, F), which, after the removal of the benzoic acid by extraction, is isolated by adjusting the pH to between 5 and 6 with concentrated ammonia (Scheme 12.52). 

It appears that nature rarely uses concerted, pericyclic reactions in biosynthesis or metabolism. However, in at least one instance a Claisen rearrangement is key to a biosynthetic pathway. It i.s, in fact, a crucial pathway, the one that biosynthesizes the amino acids phenylalanine (Phe) and tyrosine (Tyr). The pathway only exists in plants— our bodies cannot synthesize Phe and Tyr, making Phe and Tyr so-called essential amino acids. 

Chymotrypsin shows a strong preference for hydrolyzing peptide bonds formed by the carboxyl groups of the aromatic amino acids, phenylalanine, tyrosine, and tryptophan. Flowever, over time chymotrypsin also hydrolyzes amide bonds involving amino acids other than Phe, Tyr, or Trp. Peptide bonds having leucine-donated carboxyls become particularly susceptible. Thus, the specificity... 

Consult Table 18.2. The codon UUU translates to the amino acid phenylalanine. If a UUU sequence were to be mutated to UCU (the codon for serine), the protein produced would have a Ser residue in place of the Phe. Since UCU and UCC both code for Ser, a UCU UCC mutation would not lead to a change in the protein sequence. Thus, the advantage of a redundant code is that not all mutations cause disadvantageous changes in protein structure. 

Another example of a protease-catalyzed commercial process, which in this case uses the enzyme in a synthetic mode, is the completely regio- and stereoselective production of the low-caloric sweetener aspartame developed by DSM-TOSOH [15] (Fig. 7.9). Aspartame is a dipeptide consisting of the amino acids phenylalanine and aspartic acid, which are coupled by the enzyme thermolysin from Bacillus thermoproteolyticus. For an efficient coupling, relatively high temperatures are required and the amount of water in the system must be kept low to drive the reaction in the desired direction. Thermolysin, which is a metallo-endoprotease, meets these two requirements. It is thermostable, and it works in an organic solvent, which is required to keep the water activity low. In practice, however, organic solvents were not necessary, since the product aspartame forms an insoluble complex with unreacted D-Phe-OMe, which crystallizes out of the aqueous medium. 

This type of reaction can be used to invert the natural series to give a rare and expensive (R) -amino acid. Phenylalanine 4 is converted into the hydroxyacid 22 with retention. Displacement of triflate from 24 with inversion and removal of the benzyl ester gives Boc-protected (R)-Phe 26. In fact this method was used to make 15N-(/ )-Phe so the nitrogen nucleophile was labelled but it is the inversion that matters to us.8... 

Dire consequences may result if one or more of these amino acids is either absent or overabundant. For instance, a genetic disorder called phenylketonuria (PKU) is caused by the body s inability to get rid of extra phenylalanine, an amino acid abbreviated Phe. PKU is an autosomal recessive disorder, meaning that the only way to get the disease is if both of your parents carry a version of a gene linked with this disease. If only one parent has the gene linked to PKU, his or her children cannot develop the disease. Children who have... 

In a HIV-directed project, inhibitors of a protease which cleaves a polyprotein-precursor between the amino acids phenylalanine and proline are desired (27 and references therein). Therefore we designed certain peptides whose Phe-Pro unit is replaced by the isosteric fluoioolefin moiety. Scheme 3 shows the preparation for the racemic compounds. 

The abbreviations for the amino acids are phe, phenylalanine leu, leucine ile, isoleucine met, methionine val, valine ser, serine pro, proline thr, threonine ala, alanine tyr, tyrosine his, histidine gin, glutamine asn, asparagine lys, lysine asp, aspartic acid glu, glutamic acid cys, cysteine trp, tryptophan arg, arginine gly, glycine. 

The common aromatic pathway is subject to repression control of enzyme synthesis as well as the previously described control by end-product inhibition of enzyme activity. Much of the work is reviewed by Gibson and Pittard [3] and Doy [72]. Most of the studies have centered on repression control of DAMPS, the first enzyme in the pathway. The three DAMPS isoenzymes of E. coli are repressed by their specific aromatic amino acids—phenylalanine, tyrosine [107], and tryptophan [108]. In addition there is cross repression of DAMPS (tyr) synthesis by phenylalanine and tryptophan at high concentrations [107,109], and DAMPS (phe) synthesis is cross-repressed by tryptophan [109,110]. 

Inborn errors of metabolism are inherited physiologicai defects which interfere with the normal utilization of nutrients by the body. For example, phenylketonuria (PKU) may cause mental retardation due to the accumulation of phe-nylpyruvic acid, which is derived from the incomplete metabolism of the amino acid phenylalanine. Sometimes, permanent damage from these disorders may be prevented by restricting the dietary content of the nutrients which give rise to the harmful products of metabolism. In other cases. It may be necessary to provide extra amounts of certain nutrients to people who have a genetic defect which leads to poor utilization of these nutrients. 

Position 8. Position 8 is occupied by the aromatic amino acid phenylalanine. The benzene ring is required for pressor activity an inactive analogue is obtained when L-Phe is replaced by alanine or D-Phe. The free carboxyl group is also required for activity. Amide formation reduces potency to 3%. The decapeptide angiotensin I is inactive per se. 

The aromatic amino acids - tryptophan (Trp), tyrosine (Tyr) and phenylalanine (Phe) - have strong deep-UV absorption bands (A, < 230 nm) corresponding to Sq —> S2 transitions, but commonly are excited to the Sj state in fluorescence studies (Agx 260-280 nm) to minimize photoreaction and enhance fluorescence quantum yields (f). At these longer wavelengths, Trp has the largest molar extinction coefficient ( max 5600) and quantum yield (Of 0.2) of the three amino acids for Phe, the values of and Of are so poor that this species is rarely useful in fluorescence studies. When subjected to UV irradiation, proteins with both Trp and Tyr (Figure 1) typically exhibit emission spectra whose shape is characteristic of Trp residues (A ,3x 50 nm) because of nonradiative energy transfer from Tyr to Trp. 

Alanine (ala) Phenylalanine (phe) R 1 0 - HNCHC N General formula for an amino acid residue Aspartic Acid (asp)... 

On complete hydrolysis, a polypeptide gives two alanine, one leucine, one methionine, one phenylalanine, and one valine residue. Partial hydrolysis gives the following fragments Ala-Phe, Leu-Met, Val-Ala, Phe-Leu. It is known that the first amino acid in the sequence is valine and the last one is methionine. What is the complete sequence of amino acids ... 

It has long been known that peptides of bacterial origin, such as N-formylat-ed oligopeptides, are potent activators of neutrophils. Bacterial protein biosynthesis is initiated by the codon AUG, which codes for polypeptide chains at the NH2 terminus to start with N-formylmethionine. However, very few mature bacterial proteins actually have this amino acid at the NH2 terminus because Af-formylmethionine is cleaved off by proteolytic processing. Sometimes just this amino acid is cleaved, but often several adjacent residues are also removed with it. These observations formed the basis for the chemical synthesis of a variety of N-formylated oligopeptides and an assessment of their ability to activate neutrophils in vitro. The most potent of these formylated peptides is TV-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe). 

Phenylalanine Phe F 2-Amino-3-phenylpropanoic acid CSH6 - C H2 - C H(N H2) - COOH... 

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-... 

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