Phenylalanine essentiality

In mammals, tyrosine (non-essential) is synthesised from phenylalanine (essential) by reaction... 

Snyder et aL (740) prepared N>acetyl nn-phenylalanine essentially by the same procedure. 

As constituents of proteins the amino-acids are important constituents of the food of animals. Certain amino-acids can be made in the body from ammonia and non-nitrogenous sources others can be made from other amino-acids, e.g. tyrosine from phenylalanine and cystine from methionine, but many are essential ingredients of the diet. The list of essential amino-acids depends partly on the species. See also peptides and proteins. 

One ammo acid often serves as the biological precursor to another L Phenylala nine is classified as an essential ammo acid whereas its p hydroxy derivative L tyro sine IS not This is because animals can convert L phenylalanine to L tyrosine by hydrox ylation of the aromatic ring An arene oxide (Section 24 7) is an intermediate... 

The mode of action is by inhibiting 5-enolpymvyl-shikimate-3-phosphate synthase. Roundup shuts down the production of the aromatic amino acids phenylalanine, tyrosine, and tryptophane (30). Whereas all these amino acids are essential to the survival of the plant, tryptophane is especially important because it is the progenitor for indole-3-acetic acid, or auxin, which plays an important role in growth and development, and controls cell extension and organogenesis. 

Cystic fibrosis, a disease of the Caucasian population, is associated with defective CL regulation and is essentially a disorder of epithehal cells (113,114). The defect arises at several levels in the CL ion transporter, ie, the cystic fibrosis transmembrane regulation (CFTR), and is associated with defective CL transport and defective processing, whereby the protein is not correctiy incorporated into the cell membrane. The most common mutation, affecting approximately 60% of patients, is termed F 608 and designates the loss of phenylalanine at this position. This mutation appears to be at least 50,000 years old, which suggests that its survival may have had evolutionary significance (115). 

Humans are able to synthesize only 11 of the 20 amino acids in proteins, called nonessential amino acids. The other 9, called essential amino acids, are biosynthesized only in plants and microorganisms and must be obtained in our diet. The division between essential and nonessential amino acids is not clearcut, however tyrosine, for instance, is sometimes considered nonessential because humans can produce it from phenylalanine, but phenylalanine itself is essential and must be obtained in the diet. Arginine can be synthesized by humans, but much of the arginine we need also comes from our diet. 

Biological examples of pericyclic reactions are relatively rare, although one much-studied example occurs during biosynthesis in bacteria of the essential amino acid phenylalanine. Phenylalanine arises from the precursor chorismate,... 

The elimination of the amino donor, L-aspartic acid, resulted in an almost complete reduction of activity. Neither cell permeabilisation nor cofactor (pyridoxalphosphate) addition were essential for L-phenylalanine production. Maximum conversion yield occurred (100%, 22 g r) when the amino donor concentration was increased. Aspartic add was a superior amino donor to glutamic add 35 g l 1 was used. 

Tyrosine. Phenylalanine hydroxylase converts phenylalanine to tyrosine (Figure 28-10). Provided that the diet contains adequate nutritionally essential phenylalanine, tyrosine is nutritionally nonessential. But since the reaction is irreversible, dietary tyrosine cannot replace phenylalanine. Catalysis by this mixed-function oxygenase incorporates one atom of O2 into phenylalanine and reduces the other atom to water. Reducing power, provided as tetrahydrobiopterin, derives ultimately from NADPH. 

Cysteine, tyrosine, and hydroxylysine are formed from nutritionally essential amino acids. Serine provides the carbon skeleton and homocysteine the sulfur for cysteine biosynthesis. Phenylalanine hydroxylase converts phenylalanine to tyrosine. 

Not all proteins are nutritionally equivalent. Mote of some than of others is needed to maintain nittogen balance because different proteins contain different amounts of the various amino acids. The body s requirement is for specific amino acids in the correct proportions to replace the body proteins. The amino acids can be divided into two groups essential and nonessential. There are nine essential or indispensable amino acids, which cannot be synthesized in the body histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. If one of these is lacking or inadequate, then—regardless of the total intake of protein—it will not be possible to maintain nitrogen balance since there will not be enough of that amino acid for protein synthesis. 

Two amino acids—cysteine and tyrosine—can be synthesized in the body, but only from essential amino acid ptecutsots (cysteine from methionine and tyrosine from phenylalanine). The dietary intakes of cysteine and tytosine thus affect the requirements for methionine and phenylalanine. The remaining 11 amino acids in proteins are considered to be nonessential or dispensable, since they can be synthesized as long as there is enough total protein in the diet—ie, if one of these amino acids is omitted from the diet, nitrogen balance can stiU be maintained. Howevet, only three amino acids—alanine, aspartate, and glutamate—can be considered to be truly dispensable they ate synthesized from common metabolic intetmediates (pyruvate, ox-... 

Like the glucose carrier, the carriers for large neutral amino acids, the so-called L-system - now designated LAT - are present at both sides of the endothelial cell membranes and transport at least 10 essential amino acids. The L-transporter at the BBB has a much higher transport capacity than those in other tissues. Its marked preference for phenylalanine analogs explains why the anticancer drugs melphalan and d,l-NAM-7 are transported by the L-system, as is the L-Dopa used to treat Parkinson s disease [42]. 

Precursors of phenylpropanoids are synthesized from two basic pathways the shikimic acid pathway and the malonic pathway (see Fig. 3.1). The shikimic acid pathway produces most plant phenolics, whereas the malonic pathway, which is an important source of phenolics in fungi and bacteria, is less significant in higher plants. The shikimate pathway converts simple carbohydrate precursors into the amino acids phenylalanine and tyrosine. The synthesis of an intermediate in this pathway, shikimic acid, is blocked by the broad-spectrum herbicide glyphosate (i.e., Roundup). Because animals do not possess this synthetic pathway, they have no way to synthesize the three aromatic amino acids (i.e., phenylalanine, tyrosine, and tryptophan), which are therefore essential nutrients in animal diets. 

Consider one small molecule, phenylalanine. It is an essential amino acid in our diet and is important in protein synthesis (a component of protein), as well as a precursor to tyrosine and neurotransmitters. Phenylalanine is one of several amino acids that are measured in a variety of clinical methods, which include immunoassay, fluorometry, high performance liquid chromatography (HPLC see Section 4.1.2) and most recently MS/MS (see Chapter 3). Historically, screening labs utilized immunoassays or fluorimetric analysis. Diagnostic metabolic labs used the amino acid analyzer, which was a form of HPLC. Most recently, the tandem mass spectrometer has been used extensively in screening labs to analyze amino acids or in diagnostic labs as a universal detector for GC and LC techniques. Why did MS/MS replace older technological systems The answer to this question lies in the power of mass spectrometer. 

Struyve, M., Moons, M., and Tommassen, J. (1991). Carboxy-terminal phenylalanine is essential for the correct assembly of a bacterial outer membrane protein. J. Mol. Biol. 218, 141-148. 

One of the groups of theories about the origin of the genetic code states that the code has to be the way it is, and is therefore universal, for stereochemical" reasons. In other words, phenylalanine, f. ex. must be represented by the triplets UUU and UUC because phenylalanine is somehow stereochemically related to these two codons 52,53,56,57) This seems likely, since steric fit is an essential property of the processes of replication, transcription and translation. That doesn t mean that one has conclusive evidence for such a statement. It only means that the theoreticians are groping in such a direction. 

Humans have a limited capacity to synthesize amino acids de novo, but extensive interconversions can occur. Those amino acids which cannot be formed within the body and must be supplied by the diet are called essential . Members of this group, which includes the branched chain amino acids leucine and valine, and also methionine and phenylalanine, are all dietary requirements. Such essential amino acids may be chemically converted, mainly in the liver, into the non-essential amino acids. The term non-essential does not equate with not biochemically important but simply means they are not strict dietary components. 

Among protein aromatic groups, histidyl residues are the most metal reactive, followed by tryptophan, tyrosine, and phenylalanine.1 Copper is the most reactive metal, followed in order by nickel, cobalt, and zinc. These interactions are typically strongest in the pH range of 7.5 to 8.5, coincident with the titration of histidine. Because histidine is essentially uncharged at alkaline pH, complex-ation makes affected proteins more electropositive. Because of the alkaline optima for these interactions, their effects are most often observed on anion exchangers, where complexed forms tend to be retained more weakly than native protein. The effect may be substantial or it may be small, but even small differences may erode resolution enough to limit the usefulness of an assay. 

Although relatively weak, it is this last interaction that is essential for determining chiral discrimination. The superior chiral recognition achieved when ref has an aromatic side chain (Table 10) suggests that 7r-cation interactions play an important role in the stereoselectivity. Evidence for such a rr-cation interaction is observed in the CID spectra of the dimeric [A Me° ref-H]and [A -Me -ref-H] diaster-eomers, in which one ligand is an aromatic amino acid, and is supported by ab initio calculations. When an L-aromatic amino acid, such as L-phenylalanine, is used as ref, these interactions are disrupted by the side group on the a-asymmetric carbon of the L-analyte, whereas the side-chain group in the D-analyte has little steric effect on... 

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