Amino acids, essential precursors

The 10 amino acids essential in the human diet (Arg, His, He, Leu, Lys, Met, Phe, Thr, Trp, Val) are synthesized by non-human organisms by multistep pathways starting from simple metabolic precursors. Amino acid biosynthesis is controlled by feedback inhibition and suppression of synthesis of biosynthetic enzymes. The ability of an amino acid analogue to block biosynthesis of the parent amino acid often contributes to the toxicity of the analogue. Mutants resistant to the toxic effects of the analogue can be valuable tools for studying various aspects of cellular mechanism (examples to be given below). 

See also Table 5.1, Genetic Code, Glutamate as a Precursor of Other Amino Acids, Essential Amino Acids... 

One fflnino acid often serves as the biological precursor to another. L-Phenylala-nine is classified as an essential amino 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 intennediate. 

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 other nine amino acids are essential and must be taken from the diet. Notice that some of the amino acids require other amino acids for their synthesis. Exam questions usually center on whether or not an amino acid is essential and the metabolites that serve as precursors for specific amino acids. 

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. 

Deficiency of essential amino acid precursors in the diet can cause a dysregulation of neurotransmitter activity (e.g, L-tryptophan deficiency causes a decrease in 5-HT and melatonin synthesis and activity). Deficiency in essential fatty acids (e.g, omega-3 fatty acids) can cause a dysregulation of neurottansmitter... 

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. 

In addition to neutral loss scans, mass spectrometers can be used to detect other compounds in a different manner. Acylcamitines are fatty acid esters of carnitine. The masses of acylcamitines differ by the size of the fatty acid attached to it. The tandem mass spectrometer can detect these selectively as well because they all produce a similar product, in this case an ion rather than a molecule. Because it is an ion, it can be detected by the second mass separation device. The ion has a mass of 85 Da and is common to all acylcamitines. Performing a precursor ion scan of 85 Da (essentially a scan of only molecules that produce the 85 ion) reveals a selective analysis of acylcar-nitines, as shown in Fig. 14.2. Additional scans have been added to more selectively detect basic amino acids, free carnitine, short chain acylcamitines and a hormone, thyroxin (T4) which has amino acid components. 

Now here is the central nnderstanding—the role of several vitamins is to serve as coenzymes or as metabolic precursors for coenzymes that is, the vitamin itself may serve as coenzyme or it may be converted in the human body to a coenzyme. The other key point 1 suppose is obvious but 1 am going to state it anyway we need vitamins in our diet because we cannot make them ourselves. In that sense, they are like essential amino acids or essential fatty acids stuff that we need but cannot make ourselves and so must obtain from dietary sources. So let s get started in understanding these critical molecules and how they serve the needs of human beings. 

The vitamin Be family of molecules are metabolic precursors to pyridoxal phosphate, an essential coenzyme for multiple enzymes involved in amino acid metabolism. 

Second, the essential amino acids leucine, isoleucine, and phenylalanine are precursors for several additional tomato flavor elements. Here, too, these flavor elements are important flavor constituents in other fruits, including strawberries and apples. They are also found in breads, cheeses, wine, and beer. 

To provide the nutrients for proliferation of the spermatogonia and spermatocytes and maturation of the sperm. These are essential amino acids, glutamine and glucose as fuels and also as precursors for formation of nucleotides essential fatty acids for formation of phospholipids (for discussion of these topics, see Chapters 20 and 21). It is presumed that Sertoli cells extract these compounds from the blood. 

In higher plants aromatic amino acids are required not only for protein synthesis, but as precursors for hormones, and a vast diversity of phenylpropanoid or other secondary metabolites. Thus, the availability of aromatic amino acids in a number of the spatially separate compartments of the plant-cell microenvironment is essential. 

Figure 7. A serotonergic synapse including a depiction of the acute tryptophan depletion method discussed in the text. All large neutral amino acids (SLNAAs) share a common blood-brain barrier transporter. The serotonergic precursor, tryptophan, essentially competes with the other LNAAs for transport. Thus tryptophan is uniquely susceptible to acute dietary manipulation. Numerous serotonergic receptor types exist, including presynaptic S-HTm and (somatodendritic) 5-HTia autoreceptors and postsynaptic 5-HTia, 5-HTid, 5-HT2a 5-HT2c 5-HT3 and 5-HT4 receptors. Additional modulation of serotonin activity can occur via the action of selective serotonin re-uptake inhibitors (SSRls) including fluoxetine, fluvoxamine, and citalopram.

Some prominent 3-substituted derivatives include skatole (3-methylin-dole), which has a faecal odour, and indoIyl-3-acetic acid (sold as a plant rooting powder). Many indoles are biologically important for example, tryptamine is the precursor of two hormones serotonin, a vasoconstrictor, and melatonin, which is involved in the control of circadian rhythm. In addition, the amino acid tryptophan is an essential component of proteins (see Box 7.1). 

Following the initial CSF findings, other serotonergic methods have added to our knowledge of its role in aggression. Tryptophan, the essential amino acid precursor to serotonin, has been studied via depletion and... 

Reduced forms of folic acid are required for essential biochemical reactions that provide precursors for the synthesis of amino acids, purines, and DNA. Folate deficiency is not uncommon, even though the deficiency is easily corrected by administration of folic acid. The consequences of folate deficiency go beyond the problem of anemia because folate deficiency is implicated as a cause of congenital malformations in newborns and may play a role in vascular disease (see Folic Acid Supplementation A Public Health Dilemma). 

Homocysteine (Hey) metabolism is closely linked to that of the essential amino acid methionine and thus plays a central role in several vital biological processes. Methionine itself is needed for protein synthesis and donates methyl groups for the synthesis of a broad range of vital methylated compounds. It is also a main source of sulphur and acts as the precursor for several other sulphur-containing amino acids such as cystathionine, cysteine and taurine. In addition, it donates the carbon skeleton for polyamine synthesis [1,2]. Hey is also important in the metabolism of folate and in the breakdown of choline. Hey levels are determined by its synthesis from methionine, which involves several enzymes, its remethylation to methionine and its breakdown by trans-sulphuration. 

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