BC 1.1.PDF

Chapter 1: Amino Acids Lesson 1.1 Amino Acid Structure Introduction Amino 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 th...

Chapter 1: Amino Acids Lesson 1.1 Amino Acid Structure Introduction Amino 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. Glycln6 Alanln Sarlne Cy.tslne Thrconlnr (Gly,G) (acA) (Ser,9)" (cy., cl (Thr, T) coo- coo- co6- coo- coo- I I I I H3N*-C-H H3N'-C-H H3N+-C-H H3N'-C-H HsN*-c -H Fl clts CH flr, ?FI, OH SH ,o/ \r"u Vallne Leuclne lroleuclne Prollno Arpoilaio (Val,V) * (Lau, L) 0b, l) (Pro, P) {Arp, O} coo- coo- coo- coo- coo-.+ H3N--?-H I.t H3N'-C-H x^ru*-d-n H3N'-C-H I i %N"-c-H.l I crL H.C-CH r{ HrC G+l CHo. l"- -t CHo t- ttr, C}lz -o"oo fz HgC CHa cHe Asparaglne Glutamata Glulamlne tethlonlne Lyslno (A3n, il) (Glu, E) (Gh,a) (t6qil) (Ly!, K) coo- coo- coo- coo- coo- I -t I I H3N'-C -H nrru*-d-n H3N+-C-H H3N'-C-H ".*.-f tt' ?f" Y f' e'.. flle FHz xrltlc\o {z icHe G. i*' 'o'"\o \o + I ?'" cHo ".n/ ?H, [Ht Aryintno Phenyhlanlne Tyroalne Hlsffdlne Tryptophan (tus'R) (Phe, F) (Tvr, Y) (Hls, H) F p, ri4 coo- coo- c@- coo- coo- I I _l I H3N'-C-H H3N+-C-H x.,u'-l-,1 H3N'-C-H H3N+-C-H l. cH cll, cH. fz t- I a a>, fq ?q w t-8 I ffi M| l+ ?=r", Ml2 Figure 1.1 The 20 proteinogenic amino acids, arranged by increasing complexity.  ChaPter 1: Amino Acids features of the amino acids and some important This lesson provides an overview of the structural properties that arise from these features' Theproteinogenicaminoacidsshareacommonstructureca||edthebackbone.Thebackboneconsiststo the name group (also called a carboxyl group), giving rise of an amino group and a carboxylic acio tn" amino and carboxylic acid groups are both amino acid. lnthe 20 proteinogenic amino "t0,, to the this centrar carbon is direcay adjacent; or a/pha, connected to a centrar carbon ltom. Because (o-carbon), and amino acids of this known as the alpha-carbon carboxylic acid, the cenirat carbon is also form aie often called o-amino acids' amino and acids contain multiple carbons between the In contrast, some nonproteinogenic amino play carboxyl groups. These amino acids are nottypically found in proteins' though they still physiologically important roles. B-Alanine, ior exatil", i' a B-amino acid that has an amino group on its acid (GABA) is an and ptays a structural iole in the molecule'coenzyme A' y-Aminobutyric B-carbon aminoacidwithitsaminogroupontnev-c+nonandisanimportantinhibitoryneurotransmitter. to a ln addition to being bonded to the amino griup ano the carboxyl group, the q-carbon is also bonded n-grorp or tne iiOe chain (Figure 1'2)' The R-group hydrogen atom and to a variaOfe group "ulbJ'in" uniquL properties of the amino acid' determines the identity and Amino grouP j\Ti' Carboxylic acid c-H Variable side chain (R grouP) Figure 1.2 General structure of an q-amino acid' u Figurel.2depictsanaminoacidwitha||atomsinane|ectrica||yneutra|form(ie,withnoformalcharges) amino in aprotic solvents such as DMSo' However' This form can be found in amino acids dissoiveo acidsinnaturearetypicallyfoundintneaqueousenvironmentoface||,usua||yatornearpHT.4(ie' mammalian PhYsiological PH)' to lose a proton and the amino group tends to pick up a ln this environment, the carboxyl group tends at one position canceled by a has a positive charge proton, resulting in a zwitterion.(1?, a molecule that overat). Figure 1.3 shows."rriting in a moiecute that is erectricaty neutrar negative charge ut "*in"i, thJzwitterionil form of a typical amino acid' 4  Chapter 1: Amino Acids oo- \/ Carboxylate group c I Ammonium group HsN*- C H - s-carbon l'''.*- R Variable R group Figure 1.3 Zwitterionic form of an amino acid, as found in the conditions within a living cell. 1.1.02 Variable Side Chains The unique side chain of each amino acid determines ils identity and its properties, including how it cehaves 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 cther one-letter codes. For the exam, it is essential to memorize the structures of each amino acid along with the three- and one- etter codes. The folloWing amino acids are presented in order of increasing structural complexity to allow 'or 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. Glycine Glycine 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. coo- I HeN'- C- H H Figure 1.4 Predominant structure of glycine (Gly, G) at physiological pH. Alanine The next simplest amino acid is alanine, which has a methyl (-CHa) group as its side chain. The three- letter code for alanine is Ala, and the one-letter code is A. coo- I H.N*- ur C -H I cHe Figure 1.5 Predominant structure of alanine (Ala, A) at physiological pH  Chapter 1: Amino Acids group (-cHz-) alanine because they contain a methylene Most amino acids are' in a sense, derived from where alanine has its methylgroup. Serine in the form of a methylene group linked to a hydroxYl (-OH) The side chain of serine is a primary alcohol replaced by an -OH grouP in group of alanine is group. In other *orO., onl J the H atoms^in the -CHg and the one-letter code is s. serine. The three-letteicooe for serine is ser, coo- I H3N+- c- H ?" OH (Ser, s) at physiological pH' Figure 1.6 Predominant structure of serine Gysteine in its one atom'.ryLT: serine has an oxygen atom The structures of serine and cysteine differ by group' The three- i iiu tf''iof eSH) instead of a hydroxyl hydroxyl group, cysteine has sulfur utor, liuing i"tt", toi cyiteine is Cys, and the one-letter code is C' "oOL coo- I H3N"- c - H ?*' SH Figurel.TPredominantstructureofcysteine(Cys'C)atphysio|ogicalpH. Threonine Threonineisnear|yidentica|instructuretoserine,butthreoninecontainsanextramethy|group. and the alcohol' The three-letter code for threonine is Thr' Consequently, threonine contains a un.onOuiy one-letter code is T' goo- H3N'- c - H CH ,/\ HO cHs (Thr' T) at physiological pH' Figure 1.8 Predominant structure of threonine Valine threonine except that varine has a methyr group where structuraily, varine is nearry identicar to threonine, hasahydroxy|group-Trrethree-tettercooetorva|ineisVal,andtheone-|ettercodeisV.Notethatthe the letter V' chain of valine resembles arrangement of the carbon atoms in the side 6  t Chapter 1: Amino Acids r.t- " irci r Figure 1.9 Predominant structure of varine (val, v) at physiologicar pH. Leucine Leucine is similar to valine but has an extra methylene group connected to the q-carbon. The three-letter code for leucine is Leu, and the one-letter code is L. GOO- I Figure 1.10 Predominant structure of leucine (Leu, L)at physiologicar pH. lsoleucine r As its name implies, isoleueine is an isomer of leucine. In other words, isoleucine has the same molecular formula as leucine (CoHrsozN), but the atoms are arranged differenfly. In leucine, both methyl groups are attached to the sanlqcarbon, whereas in isoleucine the methyl groups are attached to different carbons. The three-letter code for isoleucine is lle (an exception to tne rule of using the first three letters of the name), and the one-letter code is l. coo- I t,r Figure 1.11 Predominant structure of isoleucine (lle, l)at physiologicalpH. Proline Proline is unique among the amino acids because its side chain connects to the backbone in twopl3ces: the q-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 secondary amine instead of a primary amine. The three-letter code for proline is Pro, and the one-letter code is p.  Chapter 1: Amino Acids goo- trT.-?-* Hoc ' cH" \,/ cHz proline (Pro' P) at physiological pF Figure 1.12 Predominant structure of ' Aspartic Acid dicarboxylic to the methylene group' forms a four-carbon Aspartic acid, with a carboxylic acid attached is typically deprotonated piotonr in water, tne sibe chain acid. Because carboxyric acids tend to ror" of the deprotonated side under physiological.ondition, and carries i"g"tiu" chgrge' ln recognition u chain,theaminoacidisoftenca||edaspartateinsteadofasparticacid' Thethree-|ettercodeforaspartate(orasparticacid)isAsp.BecauseAisa|readyusedastheone.|etter code for aspartate (or aspartic is needed. The one-retter code for aranine, a different one-retier code as reprebenting asparD ate or asparDic acid' acid) is D, which can be remembered coo- I H3N+- c -H ?n, ' ,zc\-o -o. (Asp' D)at physiological pH' Figure 1.13 Predominant structure of aspartate Asparagine has an amide' aspartate has a carboxyl group, asparagine Asparagine is similar to aspartate, but where physiological conditions' not ionize and remains n"utrat under The side chain amide of asparagine does code was Asparagine ano aspartate both lt"rt witn the same three letters, so a different three-letter code is N' which can the -NHz of the amide' The one-letter chosen for asparagin"' Arn, which highlights be remembered as the code for asparagiNe' coo- H3N'- c - H ?" c. n^ru/ \o a (Asn' N) at physiologicalpH' Figure 1.14 Predominant structure of asparagine Glutamic Acid group (giving it acid, but grutamic acid has an extra methylene Grutamic acid is nearry identicar to aspartic five carbons in total). Like aspartic a"lo, glui";i" u"',i tends to lose a proton from its side chain when in water and is commonly called glutamate' B  \ Chapter 1; Amino Acids The 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. coo- I Figure 1.15 Predominant structure of glutamate (Glu, E) at physiological pH. Glutamine 1 Like aspartate and asparagine, glutamate and glutamirE Oifer 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 -NHz 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, a) at physiological pH. Methionine Like glutamate and glutamine, methionine has two methylene Soups connected to the q-carbon. However, instead of a carboxyl group, the second methylene group is attached to a thioether-a sulfur atom that is in turn connected to an alkyl group. Specifically, methionine contains a methylthioether. The three-letter code for methionine is Met. and the oneletter code is M. coo- I Figure 1.17 Predominant structure of methionine (Met, M) at physiological pH.  ChaPter 1: ,A,mino Acids Lysine q-carbon' At the end of this carbon Lysine contains a chain of four methylene groups attached to the positive charge at physiological pH' The chain is an amino group, which is protonated and carries a for leucine, a different letter is needed three-letter code for lysine is Lys. Because L is the one-letter code code for lysine' for lysine. K is adjacent to L in the alphabet and is the one-letter coo- I H^N*-c-H 'l 9Hz I ?", GH" l-.l 9H, ' NH. pH' Figure 1.18 Predominant structure of lysine (Lys, K) at physiological Arginine quanidinium gr**p' which is protonated and Arginine contains three methylene groups attached to a sp2 carbon atom surrounded a positive cfrarge at p'hysiol6gical pH. The guanidinium group is an ""iri"r each-bonded to one or two hydrogen atoms. The three-letter code for arginine is iv irril" ,,.'itrog"n arginine' R was chosen Arg. Because A is"tor-., the one-letter code for alanine, a drfferent code is needed for sounds like R-ginine. as the one-letter code bnd can be remembered because arginine coo* I H3N*-C*H ?" cH^ l1 I ?*, NH l+ ?=*", NHz Figurel.lgPredominantstructureofarginine(Ar"g,R)atphysiologicalpH' Phenylalanine methylene group of their side chains' The remaining amino acids contain aronratic i"ings connected to the has a phenyl group (ie' a benzene ring) The simplest of these amino acids is phenylalan"ine, which is a phenyl-substituted alanine' The attached to its methylene group. In other words, phenylalanine phe. Because P is the one-letter code for proline, a different letter is three-letter code for phenilalanine is sounds like Fenylalanine' needed for phenylalanine. F was chosen because phenylalanine  Chapter 1: Amino Acids coo- I H3N+- C - H ?" A v2 Figure 1.20 Predominant structure of phenylalanine (Phe, F) at physiological pH. Tyrosine Tyrosine is identical to phenylalanine except that it contains a hydroxyl group at the pam pr:sition on the r€nzene ring (ie, it is a phenol gro*p). The three-letter code for tyrosine is Tyr. Because T is the one- etter code for threonine, a different letter is needed for tyrosine. As the second letter in the name, Y was 3hosen for the one-letter code. 'a coo- I H^N'-C-H tl cH^ r' /\ lll I OH Figure 1.21 Predominant structur6 of tyrosine (Tyr, Y) at physiological pH. Histidine.'tstidine contains a five-membered aromatic ring called imidazole attached to its methylene group. The -ng contains two nitrogen atoms and three carbon atoms. The nitrogen atoms are separated from each :fier by one of the three carbon atoms. The three-letter code for histidine is His, and the one-letter code sH. coo- I H3N'-C-H ?" FNH llu-N) Fgure 1.22 Predominant structure of histidine (His, H) at physiological pH. Tryptophan -aptophan is the only amino acid with two aromatic rings (an indole group) in its side chain. A five- rembered ring containing a nitrogen atom is connected to the methylene group, and a six-member ring is inked to the five-member ring. Two carbon atoms are shared by the rings. The three-letter code for :lptophan is Trp, a slight deviation from using the first three letters. Because T is the one-letter code for :neonine, a different letter is needed for tryptophan. W was chosen for this purpose a-nd can be by thinking of tryptophan as tWyptophan. =rnembered 11  Chapter 1: Amino Acids coo- H3N+- C * H I '& l* \* H, \_/ Figure 1.23 Predominant structure of tryptophan (Trp, W) at physiological pH, The 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 o-carbon has tetrahecjral geometry. Any (the tetrahedral atom that is bonded to four distinct groups is a chiral atom, meaning that its substituents in two distinct, nonsuperimposable (and therefore chemical groups that surround it) can be arranged nonidentical) configurations. Apart from glycine, which is achiral, all proteinogenic amino acids have four distinct substituents around possible the o-carbon; therefore, these amino acids are chiral. In other words, there are at least two forms of each amino acid except glycine. Figure 1.24 shows different ways in which the constituents of an amino acid may be arranged. o o- \ 'c I HrN.-- ? I R -:::*::.i /\ R-group in back R-grouP in front 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 ilo convention, which names molecules based on their similarity to r-- or o-glyceraldehyde (see Figure 1.25), respectively. r_-Glyceraldehyde was given its designation because it is empirically observed to be levorotatory (ie' it rotaies plane-polarized light counterclockwise), whereas o-glyceraldehyde is dextrorotatory (ie, it rotates 12  Chapter 1: Amina Acids :'ele-polarized light clockwise). Amino acids with q-carbon configurations similar to r--glyceraldehyde are -=nino acids, and amino acids that are similar to o-glyceraldehyde are o-amino acids. r ving cells, the chiral amino acids in proteins are almost exclusively r-. A few rare exceptions exist (eg, bacteria convert l-amino acids to the o-form within specific proteins). =riain CHO /*l.1r\- : =: a' = ii{": > ggct-{ : = CH..OH I = r.-Glyceraldehyde l-amino acid CHO : F :, Hl>6' g < t{t""i. = = = cH,ol-l rt o-Glyceraldehyde o-amino acid Egure 1.25 Comparison bf tfre structures of l-and o-glyceraldehyde with l- and o-amino acids. \cte that designation of an amino acid as L- or D- does nof indicate how the amino acid rotates plane- :oanzed light. Some l-amino a'bids rotate plane-polarized light clockwise, and some rotate it The designation represents onlythe structural similarity to glyceraldehyde. ='-nterclockwise. fror-rcept Check 1.'n Three different amino acids are analyzed by polarimetry. One amino acid rotates plane-polarized ight clockwise, one rotates plane-polarized light counterclockwise, and one does not rotate plane- colarized-light. What conclusions can be drawn about the stereochemistry of these amino acids? ,Assume that solutions containing chiral amino bcids have only the l-form or only the o-form (ie, :he mixtures are not racemic). Solutimm 'lcte: The appendix contains the answer. --e other convention for naming different forms of amino acids is the R/S system, which follows the -:- --,rtgch:i-i'rielag prr*rity t^ules. Under this system, all l-amino acids have S-configurations at the :-=rbon r::xcepi f{}r ilysl"ein*. The sulfur atom in cysteine's side chain increases its priority, giving the :-arbon of l-cysteine an R-configuration. Note, however, that R-cysteine is still an l-amino acid. - addition to stereochemistry at the q-carbon, two amino acids have chiral centers in their side chains. --e chiral center in the side chain of l-threonine has an R-configuration (which can be remembered as ---Reonine), whereas the chiral center in the side chain of l-isoleucine has an S-configuration --Soleucine). Their ciiestereon-rers (allothreonine and alloisoleucine) are not prevalent'in healthy -r-11?fls but may accumulate in pathological conditions.