Amino Acids - Chapter 1 PDF

Chapter 1: Amino Acids3Lesson 1.1Amino Acid StructureIntroductionAmino acids are the fundamental building blocks of proteins, which carry out nearly every necessary function of the cell. To fully understand how proteins form and how they interact with their environment, the properties of the amino a...

Chapter 1: Amino Acids3Lesson 1.1Amino Acid StructureIntroductionAmino acids are the fundamental building blocks of proteins, which carry out nearly every necessary function of the cell. To fully understand how proteins form and how they interact with their environment, the properties of the amino acids that make up proteins must first be understood. The proteinogenic amino acids, the 20 amino acids that serve as building blocks for proteins in all organisms, each have a distinct structure. This structure determines the amino acid\'s properties and contributes to interactions between a protein and its environment. The 20 proteinogenic amino acids are shown in Figure 1.1.Figure 1.1 The 20 proteinogenic amino acids, arranged by increasing complexity. Chapter 1: Amino Acids4This lesson provides an overview of the structural features of the amino acids and some important properties that arise from these features.1.1.01 Amino Acid BackboneThe proteinogenic amino acids share a common structure called the backbone. The backbone consists of an and a (also called a carboxyl group), giving rise to the name amino acid. In the 20 proteinogenic amino acids, the amino and carboxylic acid groups are both connected to a central carbon atom. Because this central carbon is directly adjacent, or alpha, to the carboxylic acid, the central carbon is also known as the alpha-carbon (α-carbon), and amino acids of this form are often called α-amino acids.In contrast, some nonproteinogenic amino acids contain multiple carbons between the amino and carboxyl groups. These amino acids are not typically found in proteins, though they still play physiologically important roles. β-Alanine, for example, is a that has an amino group on its β-carbon and plays a structural role in the molecule coenzyme A. γ-Aminobutyric acid (GABA) is an amino acid with its amino group on the γ-carbon and is an important inhibitory neurotransmitter.In addition to being bonded to the amino group and the carboxyl group, the α-carbon is also bonded to a hydrogen atom and to a variable group called the R-group or the side chain (Figure 1.2). The R-group determines the identity and unique properties of the amino acid.Figure 1.2 General structure of an α-amino acid.Figure 1.2 depicts an amino acid with all atoms in an electrically neutral form (ie, with no ). This form can be found in amino acids dissolved in aprotic solvents such as DMSO. However, amino acids in nature are typically found in the aqueous environment of a cell, usually at or near pH 7.4 (ie, mammalian physiological pH).In this environment, the carboxyl group tends to lose a proton and the amino group tends to pick up a proton, resulting in a zwitterion (ie, a molecule that has a positive charge at one position canceled by a negative charge at another, resulting in a molecule that is electrically neutral overall). Figure 1.3 shows the zwitterionic form of a typical amino acid. Chapter 1: Amino Acids5Figure 1.3 Zwitterionic form of an amino acid, as found in the conditions within a living cell.1.1.02 Variable Side ChainsThe unique side chain of each amino acid determines its identity and its properties, including how it behaves when it is part of a protein. The name of each amino acid can be abbreviated using either a three-letter code or a one-letter code as summarized in Figure 1.1.For most amino acids, the three-letter code is the first three letters of its name, with a few exceptions detailed in the following list of amino acids. The one-letter code is the first letter of the amino acid name where possible, but in cases where multiple amino acids start with the same letter, some are assigned other one-letter codes.For the exam, it is essential to memorize the structures of each amino acid along with the three- and one-letter codes. The following amino acids are presented in order of increasing structural complexity to allow for the memorization of the simple structures first. These can then be built upon to learn the more complex structures. The structures of the amino acids are shown in Figures 1.4 through 1.23.GlycineGlycine is the simplest of the amino acids and perhaps the easiest structure to remember. Glycine\'s side chain is a hydrogen atom. The three-letter code for glycine is Gly, and the one-letter code is G.Figure 1.4 Predominant structure of glycine (Gly, G) at physiological pH.AlanineThe next simplest amino acid is alanine, which has a methyl (--CH3) group as its side chain. The three-letter code for alanine is Ala, and the one-letter code is A.Figure 1.5 Predominant structure of alanine (Ala, A) at physiological pH. Chapter 1: Amino Acids6Most amino acids are, in a sense, derived from alanine because they contain a methylene group (--CH2--) where alanine has its methyl group.SerineThe side chain of serine is a in the form of a methylene group linked to a hydroxyl (--OH) group. In other words, one of the H atoms in the --CH3 group of alanine is replaced by an --OH group in serine. The three-letter code for serine is Ser, and the one-letter code is S.Figure 1.6 Predominant structure of serine (Ser, S) at physiological pH.CysteineThe structures of serine and cysteine differ by one atom. Where serine has an oxygen atom in its hydroxyl group, cysteine has a sulfur atom, giving it a thiol (--SH) instead of a hydroxyl group. The three-letter code for cysteine is Cys, and the one-letter code is C.Figure 1.7 Predominant structure of cysteine (Cys, C) at physiological pH.ThreonineThreonine is nearly identical in structure to serine, but threonine contains an extra methyl group. Consequently, threonine contains a. The three-letter code for threonine is Thr, and the one-letter code is T.Figure 1.8 Predominant structure of threonine (Thr, T) at physiological pH.ValineStructurally, valine is nearly identical to threonine, except that valine has a methyl group where threonine has a hydroxyl group. The three-letter code for valine is Val, and the one-letter code is V. Note that the arrangement of the carbon atoms in the side chain of valine resembles the letter V. Chapter 1: Amino Acids7Figure 1.9 Predominant structure of valine (Val, V) at physiological pH.LeucineLeucine is similar to valine but has an extra methylene group connected to the α-carbon. The three-letter code for leucine is Leu, and the one-letter code is L.Figure 1.10 Predominant structure of leucine (Leu, L) at physiological pH.IsoleucineAs its name implies, isoleucine is an of leucine. In other words, isoleucine has the same molecular formula as leucine (C6H13O2N), but the atoms are arranged differently. In leucine, both methyl groups are attached to the same carbon, whereas in isoleucine the methyl groups are attached to different carbons. The three-letter code for isoleucine is Ile (an exception to the rule of using the first three letters of the name), and the one-letter code is I.Figure 1.11 Predominant structure of isoleucine (Ile, I) at physiological pH.ProlineProline is unique among the amino acids because its side chain connects to the backbone in two places: the α-carbon (as in all amino acids) and the backbone nitrogen, forming a five-membered ring. Because of this feature, proline is the only proteinogenic amino acid that has a instead of a primary amine. The three-letter code for proline is Pro, and the one-letter code is P. Chapter 1: Amino Acids8Figure 1.12 Predominant structure of proline (Pro, P) at physiological pH.Aspartic AcidAspartic acid, with a carboxylic acid attached to the methylene group, forms a four-carbon dicarboxylic acid. Because carboxylic acids tend to lose protons in water, the side chain is typically deprotonated under physiological conditions and carries a negative charge. In recognition of the deprotonated side chain, the amino acid is often called aspartate instead of aspartic acid.The three-letter code for aspartate (or aspartic acid) is Asp. Because A is already used as the one-letter code for alanine, a different one-letter code is needed. The one-letter code for aspartate (or aspartic acid) is D, which can be remembered as representing asparDate or asparDic acid.Figure 1.13 Predominant structure of aspartate (Asp, D) at physiological pH.AsparagineAsparagine is similar to aspartate, but where aspartate has a carboxyl group, asparagine has an. The side chain amide of asparagine does not ionize and remains neutral under physiological conditions. Asparagine and aspartate both start with the same three letters, so a different three-letter code was chosen for asparagine: Asn, which highlights the --NH2 of the amide. The one-letter code is N, which can be remembered as the code for asparagiNe.Figure 1.14 Predominant structure of asparagine (Asn, N) at physiological pH.Glutamic AcidGlutamic acid is nearly identical to aspartic acid, but glutamic acid has an extra methylene group (giving it five carbons in total). Like aspartic acid, glutamic acid tends to lose a proton from its side chain when in water and is commonly called glutamate. Chapter 1: Amino Acids9The three-letter code for glutamate (or glutamic acid) is Glu. Because G is the one-letter code for glycine, E was chosen as the one-letter code for glutamate (or glutamic acid) because alphabetically it comes after D, the one-letter code for the similar aspartate molecule.Figure 1.15 Predominant structure of glutamate (Glu, E) at physiological pH.GlutamineLike aspartate and asparagine, glutamate and glutamine differ only in that glutamine has an amide where glutamate has a carboxyl group. Glu is the three-letter code for glutamate, so a different code is needed for glutamine. Gln was chosen, which highlights the --NH2 of the amide. The one-letter code for glutamine is Q, which can be remembered because glutamine sounds similar to Q-tamine.Figure 1.16 Predominant structure of glutamine (Gln, Q) at physiological pH.MethionineLike glutamate and glutamine, methionine has two methylene groups connected to the α-carbon. However, instead of a carboxyl group, the second methylene group is attached to a ---a sulfur atom that is in turn connected to an alkyl group. Specifically, methionine contains a methyl thioether. The three-letter code for methionine is Met, and the one-letter code is M.Figure 1.17 Predominant structure of methionine (Met, M) at physiological pH. Chapter 1: Amino Acids10LysineLysine contains a chain of four methylene groups attached to the α-carbon. At the end of this carbon chain is an amino group, which is protonated and carries a positive charge at physiological pH. The three-letter code for lysine is Lys. Because L is the one-letter code for leucine, a different letter is needed for lysine. K is adjacent to L in the alphabet and is the one-letter code for lysine.Figure 1.18 Predominant structure of lysine (Lys, K) at physiological pH.ArginineArginine contains three methylene groups attached to a , which is protonated and carries a positive charge at physiological pH. The guanidinium group is an sp2 carbon atom surrounded by three nitrogen atoms, each bonded to one or two hydrogen atoms. The three-letter code for arginine is Arg. Because A is the one-letter code for alanine, a different code is needed for arginine. R was chosen as the one-letter code and can be remembered because arginine sounds like R-ginine.Figure 1.19 Predominant structure of arginine (Arg, R) at physiological pH.PhenylalanineThe remaining amino acids contain connected to the methylene group of their side chains. The simplest of these amino acids is phenylalanine, which has a phenyl group (ie, a benzene ring) attached to its methylene group. In other words, phenylalanine is a phenyl-substituted alanine. The three-letter code for phenylalanine is Phe. Because P is the one-letter code for proline, a different letter is needed for phenylalanine. F was chosen because phenylalanine sounds like Fenylalanine. Chapter 1: Amino Acids11Figure 1.20 Predominant structure of phenylalanine (Phe, F) at physiological pH.TyrosineTyrosine is identical to phenylalanine except that it contains a hydroxyl group at the on the benzene ring (ie, it is a ). The three-letter code for tyrosine is Tyr. Because T is the one-letter code for threonine, a different letter is needed for tyrosine. As the second letter in the name, Y was chosen for the one-letter code.Figure 1.21 Predominant structure of tyrosine (Tyr, Y) at physiological pH.HistidineHistidine contains a five-membered aromatic ring called attached to its methylene group. The ring contains two nitrogen atoms and three carbon atoms. The nitrogen atoms are separated from each other by one of the three carbon atoms. The three-letter code for histidine is His, and the one-letter code is H.Figure 1.22 Predominant structure of histidine (His, H) at physiological pH.TryptophanTryptophan is the only amino acid with two aromatic rings (an ) in its side chain. A five-membered ring containing a nitrogen atom is connected to the methylene group, and a six-member ring is linked to the five-member ring. Two carbon atoms are shared by the rings. The three-letter code for tryptophan is Trp, a slight deviation from using the first three letters. Because T is the one-letter code for threonine, a different letter is needed for tryptophan. W was chosen for this purpose and can be remembered by thinking of tryptophan as tWyptophan. Chapter 1: Amino Acids12Figure 1.23 Predominant structure of tryptophan (Trp, W) at physiological pH.1.1.03 Amino Acid StereochemistryThe amino acids are often represented in two dimensions, causing them to appear flat. In reality, the amino acids are three-dimensional objects in which the α-carbon has. Any tetrahedral atom that is bonded to four distinct groups is a chiral atom, meaning that its substituents (the chemical groups that surround it) can be arranged in two distinct, nonsuperimposable (and therefore nonidentical) configurations.Apart from , which is , all proteinogenic amino acids have four distinct substituents around the α-carbon; therefore, these amino acids are chiral. In other words, there are at least two possible forms of each amino acid except glycine. Figure 1.24 shows different ways in which the constituents of an amino acid may be arranged.Figure 1.24 Two possible configurations of a typical amino acid.Two conventions are commonly used to distinguish amino acid isomers. The first is the ʟ/ᴅ convention, which names molecules based on their similarity to ʟ- or ᴅ-glyceraldehyde (see Figure 1.25), respectively. ʟ-Glyceraldehyde was given its designation because it is empirically observed to be levorotatory (ie, it rotates plane-polarized light counterclockwise), whereas ᴅ-glyceraldehyde is dextrorotatory (ie, it rotates Chapter 1: Amino Acids13plane-polarized light clockwise). Amino acids with α-carbon configurations similar to ʟ-glyceraldehyde are ʟ-amino acids, and amino acids that are similar to ᴅ-glyceraldehyde are ᴅ-amino acids.In living cells, the chiral amino acids in proteins are almost exclusively ʟ. A few rare exceptions exist (eg, certain bacteria convert ʟ-amino acids to the ᴅ-form within specific proteins).Figure 1.25 Comparison of the structures of ʟ-and ᴅ-glyceraldehyde with ʟ- and ᴅ-amino acids.Note that designation of an amino acid as ʟ- or ᴅ- does not indicate how the amino acid rotates plane-polarized light. Some ʟ-amino acids rotate plane-polarized light clockwise, and some rotate it counterclockwise. The designation represents only the structural similarity to glyceraldehyde.Concept Check 1.1Three different amino acids are analyzed by polarimetry. One amino acid rotates plane-polarized light clockwise, one rotates plane-polarized light counterclockwise, and one does not rotate plane-polarized-light. What conclusions can be drawn about the stereochemistry of these amino acids? Assume that solutions containing chiral amino acids have only the ʟ-form or only the ᴅ-form (ie, the mixtures are not racemic).The other convention for naming different forms of amino acids is the R/S system, which follows the. Under this system, all ʟ-amino acids have S-configurations at the α-carbon. The sulfur atom in cysteine\'s side chain increases its priority, giving the α-carbon of ʟ-cysteine an R-configuration. Note, however, that R-cysteine is still an ʟ-amino acid.In addition to stereochemistry at the α-carbon, two amino acids have chiral centers in their side chains. The chiral center in the side chain of ʟ-threonine has an R-configuration (which can be remembered as ʟ-thReonine), whereas the chiral center in the side chain of ʟ-isoleucine has an S-configuration (ʟ-iSoleucine). Their (allothreonine and alloisoleucine) are not prevalent in healthy humans but may accumulate in pathological conditions.