Naturally Occurring Amino Acids

Glutamic Acid A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. 

Fig.1. Chemical structures of fluorinated analogues of amino acids naturally occurring in proteins and labelled with fluorine-18.

This process was developed in order to synthesize unnatural a-amino acids. Naturally occurring, enantiomerically pure amino acids, as well as achiral glycine, have been used as starting materials in order to enantioselectively introduce a-substituents1 14. The resulting cyclic esters and amides have been alkylated and subjected to aldol reactions1-14. 

Stereochemistry of Amino Acids Naturally occurring amino acids belong to the T-family. That is, when the amino acid is drawn as a Fischer projection, with the carboxyl group at the top and the side chain at the bottom, the amino group is on the left, as shown in Figure 12.45. 

The third mechanism is represented by nonmodular one-step peptide synthesis. Enzymes belonging to this group catalyze the biosynthesis of poly(amino acids). Naturally occurring poly(amino acids) comprise cyanophy-cin [multi-L-arginyl-poly-(L-aspartic acid) cyanophycin granule polypeptide, (CGP)], (poly-(e-lysine) (PL), and poly-(y-glutamate) (PGA). As a consequence of non-ribosomal biosynthesis these peptides reveal a polydisperse mass distribution. 

Proteins are built of peptide units, the amino acids, whose side chains give the structural feature and therefore the functional properties to the molecule. Among the amino acids naturally occurring in proteins, one can distinguish between polar and nonpolar ones. 

Most biological catalysts are enzymes, i.e., proteins, which are macromolecules (polypeptides) fonned by biopolymerization of amino acids (with elimination of water) some enzymes are huge, with hundreds of monomer units. The 20 amino acid monomers occurring in nature. 

All amino acids except glycine exist in these two different isomeric forms but only the L isomers of the a-amino acids are found in proteins, although many D amino acids do occur naturally, for example in certain bacterial cell walls and polypeptide antibiotics. It is difficult to differentiate between the D and the L isomers by chemical methods and when it is necessary to resolve a racemic mixture, an isomer-specific enzyme provides a convenient way to degrade the unwanted isomer, leaving the other isomer intact. Similarly in a particular sample, one isomer may be determined in the presence of the other using an enzyme with a specificity for the isomer under investigation. The other isomer present will not act as a substrate for the enzyme and no enzymic activity will be demonstrated. The enzyme L-amino acid oxidase (EC 1.4.3.2), for example, is an enzyme that shows activity only with L amino acids and will not react with the D amino acids. 

In 1974 Garay and Hrasko [13] contended that PVEDs between enantiomers would, in the course of millions of years of evolution, lead to almost complete selection of one isomer, and in 1975 Letokhov [14] asserted that PVED-generated rate differences as small as 10-16 would over 10s to 109 years be quite sufficient for full selection of either of the two stereoisomeric forms of all the amino acids that occur in animate nature. In 1983 Kondepudi and Nelson [15] claimed that a value of AE/kTof 1017 to 1(T15 is sufficient to have a strong chiral selectivity. ... 

Sulfur is a constituent of two amino acids that occur in proteins, cysteine and methionine (chapter 10), and occurs in a large number of additional natural products, several of which we will encounter in what follows. 

Here is an important point almost all chiral amino acids that occur naturally in proteins throughout all of nature have L-stereochemistry. Why has nature uniquely selected L-amino acids for the construction of proteins No one knows for sure. In passing, we note that D-amino acids do occur in some living systems. The cell walls of bacteria possess both d- and L-amino acids, for example. However, these are introduced in a manner distinct from that employed to synthesize proteins. 

Although free amino acids and those in proteins in eukaryotes are entirely of the L-form (except glycine, which is not optically active), D-amino acids do occur in nature, for example in bacterial cell walls (D-alanine and D-glutamate). Consequently, they enter the body from bacteria in food and from the digestion of bacteria in the... 

For example, the two configurations of the amino acid, alanine, would be represented in perspective or projection as 15 and 16. The carboxyl carbon is CI and is placed at the top. The substituents at the chiral carbon connected to the horizontal bonds are amino (—NH2) and hydrogen. The amino substituent is taken to be the main substituent when this is on the left the acid has the l configuration, and when it is on the right, the d configuration. All of the amino acids that occur in natural proteins have been shown to have the L configuration. 

The amino acids that occur naturally as constituents of proteins have an amino group (NH2) and a carboxylic acid group (C02H) attached to the same... 

The most abundant amino acids are those that are protein constituents and these are always a-amino acids. However, there are many other amino acids that occur naturally in living systems that are not constituents of proteins, and are not a-amino acids. Many of these are rare, but others are common and play important roles in cellular metabolism. For example, 3-aminopropanoic acid is a precursor in the biosynthesis of the vitamin, pantothenic acid,2... 

Stereochemistry in Biological Systems. Amino acids occur naturally in both D and L (R and S) enantiomeric configurations. Amino acids that occur in proteins almost always have the L configuration although amino acids that occur in bacterial peptides may have the enantiomeric D configuration. The two configurations are shown in Figure 1.21 for alanine. 

Twenty standard amino acids commonly occur in nature. They differ in the structure of the side chain that is attached to the a-carbon (the R group in the previous structure). Table 26.1 shows the structures of the standard amino acids at pFI 7, along with their names and abbreviations. 

The 20 amino acids that occur naturally in proteins differ in the identity of the R group bonded to the a carbon. The simplest amino acid, called glycine, has R = H. When the R group is any other substituent, the a carbon is a sterer enic center, and there are two possible enantiomers. 

With neuraminic acid, a sugar amino acid widely occurring naturally as Ai-acetylneuraminic acid, an amide-linked (1 5)-dimer 21 (O Scheme 6) and the corresponding 2,3-ene analogue were prepared [30], On a solid phase, even an octamer 22 was available [31]. 

Amino acids are small organic molecules that posses both an amino and a carboxyl group. Amino acids occur in nature in a multitude of biological forms, either free or conjugated to various types of compounds, or as the building blocks of proteins. The amino acids that occur in proteins are named a-amino acids and have the empirical formula RCH(NH2)COOH. Only 20 amino acids are used in nature for the biosynthesis of the proteins, because only 20 amino acids are coded by the nucleic acids. 

Go to Appendix C. If you are using a TI-83 Plus, you can download the program PEPTIDE and run the application as directed. If you are using another calculator, your teacher will provide you with keystrokes to use. There are 20 amino acids that occur in proteins found in nature. The program will prompt you to input a number of amino acids. After you do, press ENTER. The program will respond with the number of different straight-chain polypeptides possible given that number of amino acid units, a. Aspartame is an artificial sweetener that is a dipeptide, a protein made of two amino acids. How many possible dipeptides are there ... 

TiTost of the amino acids which occur in the proteins of organisms, and also a few nonprotein amino acids, have been found dissolved in natural waters (1, 2, 3, 4, 5, 6,7, 8, 9). The concentrations range from about 1 to 20 fig per liter. These dissolved amino acids differ from the amino acids associated with the particulate organic matter in natural waters in that they are free and not bound in a peptide or polymeric linkage. Table I summarizes some of the amino acids and concentrations which have been reported. Amino acids not included in the table but which may be present in low concentrations in natural waters include... 

Phenylalanine is one of the 10 essential amino acids that must be obtained from outside the body, as distinguished from the 11 nonessential amino acids that occur naturally within the body, including tyrosine. Exclusive of the nonessential amino add hydroxyproline, both sets comprise 20 common amino adds that are found in aU proteins, and they conform with, or are derived from, the common genetic code. It may be further noted that a large array of alkaloids are derived from phenylalanine and tyrosine, according to Cordell s Introduction to Alkaloids, as presented by Hoffman (1999, p. 145). 

The PLP-dependent racemization of amino acids also occurs with the abstraction of the a-proton of the substrate, allowing similar inactivation approaches to be pursued. Walsh and co-workers have examined the reaction of alanine race-mases from several sources with /3-substituted alanines (Roise et al., 1984 Badet et al., 1984 Wang and Walsh, 1978, 1981). The partition ratio was found to be invariant with the stereochemistry of the a-carbon and the nature of the leaving group, indicating that a common intermediate was formed which did not recall... 

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