PROTEINS Notes

1 INTRODUCTIONP roteins are the most abundant biological macromolecules, occurring in all cellsand all parts of cells. Amino acids are the building blocks of PROTEINS . Allproteins, whether from the most ancient lines of bacteria or from the mostcomplex forms of life, are constructed from the same set of 20 amino acids. Whatis most remarkable is that cells can produce PROTEINS with strikingly differentproperties and activities by joining the same 20 amino acids in many differentcombinations and sequences. From these building blocks different organismscan make such widely diverse products as enzymes, hormones, antibodies,transporters, muscle fibers, the lens protein of the eye, feathers, spider webs,rhinoceros horn, milk PROTEINS , antibiotics, and mushroom poisons and othersubstances having distinct biological activities.

2 While PROTEINS contain onlyL- -amino acids, microorganisms elaborate peptides that contain both D- andL- -amino reading this lesson , you will be able tozdescribe amino acidszexplain the structure of amino acidszclassify amino acidszdescribe proteinszdescribe the structure of proteinzexplain the function of proteinszexplain the digestion and absorption of proteinszdescribe products of amino acidszexplain transamination, Deamination, Urea CycleBIOCHEMISTRYMODULEP roteinsBiochemistry AMINO ACIDSP roteins are the essential agents of biological function, and amino acids are thebuilding blocks of PROTEINS . The diversity of the thousands of PROTEINS found innature arises from the commonly occurring 20 amino acids. PROTEINS arepolymers of amino acids, with each amino acid residue joined to its neighborby a specific type of covalent bond.

3 PROTEINS can be broken down (hydrolyzed)to their constituent amino acids the free amino acids derived from them. Of theover 300 naturally occurring amino acids, 20 constitute the monomer units ofproteins. All 20 amino acids (Table ) are biologically essential. Humans cansynthesize 12 (nutritionally nonessential) of the 20 common amino acids fromthe amphibolic intermediates of glycolysis and of the citric acid cycle. Of the12 nutritionally nonessential amino acids, nine are formed from amphibolicintermediates and three (cysteine, tyrosine and hydroxylysine) from nutritionallyessential amino List of essential and nonessential amino acidsEssentialNonessentialHistidineAlani neIsoleucineArginineLeucineAspartic acidLysineCysteineMethionineGlutamic acidPhenylalanineGlutamineThreonineGlyci neTryptophanProlineValineSerineTyrosineA sparagineSelenocysteinePyrrolysineEssent ial amino acids are "essential" not because they are more important to lifethan the others, but because the body does not synthesize them.

4 They must bepresent in the diet or they will not be present in the body. In addition, the aminoacids arginine, cysteine, glycine, glutamine, histidine, proline, serine andtyrosine are considered conditionally essential, meaning they are not normallyrequired in the diet, but must be supplied exogenously to specific populationsthat do not synthesize them in adequate amounts. 47 ProteinsBIOCHEMISTRYMODULEB iochemistryNotesSelenocysteine, while not normally considered an amino acid present in PROTEINS ,selenocysteine occurs at the active sites of several enzymes. Examples includethe human enzymes thioredoxin reductase, glutathione peroxidase, and thedeiodinase that converts thyroxine to triiodothyronine. Pyrrolysine sometimesconsidered the 22nd amino acid , is not listed here as it is not used by Amino Acids are Chiral MoleculesAn -amino acid consists of a central carbon atom, called the carbon, linkedto an amino group, a carboxylic acid group, a hydrogen atom, and a distinctiveR group.

5 For all the common amino acids except glycine, the carbon is bondedto four different groups: a carboxyl group, an amino group, an R group, and ahydrogen atom (Fig. ; in glycine, the R group is another hydrogen atom). The -carbon atom is thus a chiral center. Because of the tetrahedral arrangementof the bonding orbitals around the -carbon atom, the four different groups canoccupy two unique spatial arrangements, and thus amino acids have two possiblestereoisomers. Since they are nonsuperimposable mirror images of each other(Fig. ), the two forms represent a class of stereoisomers called enantiomers(Fig. ). The R group is often referred to as the side chain. Enantiomericmolecules display a special property called optical activity the ability to rotatethe plane of polarization of plane-polarized light.

6 Clockwise rotation of incidentlight is referred to as dextrorotatory (D) behavior, and counterclockwiserotation is called levorotatory (L) behavior. Only L amino acids are constituentsof PROTEINS . The magnitude and direction of the optical rotation depend on thenature of the amino acid side +HRCOO CFig. : General structure of an amino acid. This structure is common to all but one ofthe -amino acids. (Proline, a cyclic amino acid, is the exception.) The R group or sidechain (red) attached to the carbon (blue) is different in each amino : The L and D Isomers of Amino Acids. R refers to the side chain. The L and Disomers are mirror images of each 48 NotesHCCOO HN3+CH3L-AlanineCCOO CH3D-AlanineH+3 NHFig. : Stereoisomerism in a-amino acids.

7 The two stereoisomers of alanine, L- andD-alanine, are nonsuperimposable mirror images of each other (enantiomers). structure of a Typical Amino AcidAmino acids in solution at neutral pH exist predominantly as dipolar ions (alsocalled zwitterions). Amino acids can exist as zwitterions - substances containingequal numbers of positive and negative charge due to their carboxyl and aminegroups, which can be negatively and positively charged, respectively. In thedipolar form, the amino group is protonated (NH3+) and the carboxyl group isdeprotonated (COO ). The ionization state of an amino acid varies with pH(Figure ). They differ from each other in their side chains, or R groups, whichvary in structure , size, and electric charge, and which influence the solubility ofthe amino acids in : Ionization State as a Function of pH.

8 The ionization state of amino acids isaltered by a change in pH. The zwitterionic form predominates near physiological Amino Acids can join via Peptide BondsThe crucial feature of amino acids that allows them to polymerize to formpeptides and PROTEINS is the existence of their two identifying chemical groups: 49 ProteinsBIOCHEMISTRYMODULEB iochemistryNotesthe amino (NH3+) and carboxyl (COO ) groups. The amino and carboxyl groupsof amino acids can react in a head-to-tail fashion, eliminating a water moleculeand forming a covalent amide linkage, which, in the case of peptides andproteins, is typically referred to as a peptide CLASSIFICATIONThe structures and abbreviations for the 20 amino acids commonly found inproteins are shown in Figure All the amino acids except proline have bothfree amino and free carboxyl groups.

9 The classifications of amino acids is basedon the polarity of the side chains. Thus, the structures shown in Figure aregrouped into the following categories: (1) nonpolar or hydrophobic amino acids,(2) neutral (uncharged) but polar amino acids, (3) acidic amino acids (whichhave a net negative charge at pH ), and (4) basic amino acids (which havea net positive charge at neutral pH). Nonpolar Amino AcidsThe nonpolar amino acids include all those with alkyl chain R groups (alanine,valine, leucine, and isoleucine), as well as proline (with its unusual cyclicstructure), methionine (one of the two sulfur-containing amino acids), and twoaromatic amino acids, phenylalanine and tryptophan. Tryptophan is sometimesconsidered a borderline member of this group because it can interact favorablywith water via the N H moiety of the indole ring.

10 Proline, strictly speaking, isnot an amino acid but rather an -imino Polar, Uncharged Amino AcidsThe polar, uncharged amino acids except for glycine contain R groups that canform hydrogen bonds with water. Thus, these amino acids are usually moresoluble in water than the nonpolar amino acids. Tyrosine displays the lowestsolubility in water of the 20 common amino acids. Glycine, the simplest aminoacid, has only a single hydrogen for an R group, and this hydrogen is not a goodhydrogen bond former. Glycine s solubility properties are mainly influenced byits polar amino and carboxyl groups, and thus glycine is best considered amember of the polar, uncharged group. It should be noted that tyrosine hassignificant nonpolar characteristics due to its aromatic ring and could arguablybe placed in the nonpolar Acidic Amino AcidsThere are two acidic amino acids aspartic acid and glutamic acid whose Rgroups contain a carboxyl group.