Amino Acids and Peptides Chapter 3

Why is it important to specify the three dimensional structure of amino acids? α-carbon has amino group and carboxyl group R-group – identity to amino acid Also bond to hydrogen Amino and carboxyl groups are adjacent to each other. R group and hydrogen are adjacent to each other. This is two dimensional formula conveying the simple structure of an amino acid

What is Stereochemistry? Nonsuperimposable mirror images – Chiral All protein-derived amino acids have at least one stereocenter (the α-carbon) and are chiral (stereoisomers) – except glycine Two stereoisomers of amino acids are designated L- or D- All amino acids are chiral giving rise to two nonsuperimposable mirror images. All have four different groups except glycine. Based on glyceraldehyde , the two stereoisomers or two possibilities of nonsuperimposable mirror images of amino acids – the Left/laevus form of glyceraldehyde has hydroxyl group on left side of molecule and D form has it on right side/dexter. Ability of optically active compounds to rotate polarized light to left or right

Amino acid structures (figure 3.3) The position of amino group on left or right side of alpha carbon determines the L or D designation L-amino acids are found in all proteins; D-amino acid image found in proline D-amino acids are found in nature Three letter or one-letter codes – refer to amino acids Memorize table 3.1

Why are amino acid side chains so important? Side chains – classification of amino acids Polar and nonpolar nature of side chain Acidic or basic group in side chain Nature of functional groups in side chains Side chain – simplest in glycine Can be larger and complex Carbon atoms – β-, γ-, ε-, δ- and ω- carbons (refer to lysine in figure 3.3) Aa are classified on basis of their side chains. Some are polar and some are non polar. Some can be acidic or basic. These two are the main critieria for classifying the aa. Some can have other functional groups besides being acide or basic. In most aa the side chains are larger and more compex but glycine has simplest side chain. Amino acids have individual amino acids. Omega represents terminal carbon

Which amino acids have nonpolar side chains? (Group 1) Nonpolar side chains – Ala, Val, Leu, Ile, Pro, Phe, Trp and Met Ala, Val, Leu, Ile. Pro – aliphatic hydrocarbon group- (absence of a benzene ring) - Proline has cyclic aliphatic structure Proline – nitrogen is bonded to two carbon atoms

Which amino acids have nonpolar side chains? (Group 1) Phenylalanine – hydrocarbon is aromatic (contains cyclic group similar to benzene ring) Trp – aromatic indole ring side chain Met – Sulfur + aliphatic hydrocarbon groupings in side chain

Which amino acids have electrically neutral polar side chains Which amino acids have electrically neutral polar side chains? (group 2) Neutral polar side chains – electrically neutral (uncharged) at neutral pH Ser, Thr, Tyr, Cyc, Glu, Asn

Which amino acids have electrically neutral polar side chains Which amino acids have electrically neutral polar side chains? (group 2) Ser, Thr – polar hydroxyl (-OH) group Tyr – hydroxyl group bonded to aromatic hydrocarbon group Cys – thiol group (-SH) Gln, Asn – amide bonds

Which amino groups have carboxyl groups in their side chains? (Group 3) Acidic side chains – Glutamic acid (Glu) and Aspartic acid (Asp) Carboxyl group (in addition to one already present) Lose a proton to form – carboxylate anion Negatively charged at neutral pH These have a carboxyl group in addition to a carboxyl group already in Glu and Asp. These lose a proton to form carboxylate anions – glutamate and aspartate. These ions give these aa a negative charge at neutral pH

Which amino acids have basic side chains? Basic side chains – His, Lys, Arg Positively charged at or near neutral pH Lys – NH3 group is attached to an aliphatic hydrocarbon chain Arg – Guanidino group His – Imidazole group

Amino acid summary α carbon present in 20 amino acids α amino group is primary (19 aa) and secondary in proline α carbon is stereo centre in all except glycine Isoleucine and threonine – second stereo center Letter codes in table 3.1

Uncommon amino acids Why some amino acids are found less commonly in proteins? Produced by modification of parent amino acid in posttranslation

Uncommon amino acids Why amino acids are found less commonly in proteins? Hydroxylysine and Hydroxyproline differ from parent by having hydroxyl groups on their side chains- found in connective-tissue proteins-collagen Thyroxine has extra iodine-containing aromatic group- found in thyroid glands OH bond to CH is the post translation modification. Thyroxine is the modification of tyrosine. Has extra iodine containing aromatic groups.

What are zwitterions? Amino acids without charged groups on their side chains – exist in neutral solution – zwitterions - with no net charge Zwitterions have equal positive and negative charges at neutral pH – electrically neutral Carboxylate groups are negatively charged and aminogroups are positively charged. Some aa are without any charged groups on their side chains. These occur in neutral solution –zwitter ions.

Why aminoacids can act as both acids and bases? The pKa values of α carboxyl groups are 2 The pKa values of amino group are 9 to 10.5 The classification of aa as acidic or basic depends on pKa of side chain as well as chemical nature of group

Why aminoacids can act as both acids and bases? Histidine, Lysine and arginine – basic aa – amino group - high pKa Aspartic acid and glutamic acid – acidic aa – carboxylic side chains – low pKa Have titratable protons. Some side chains do as well In amino acid, carboxyl group (-) and amino group (+) are charged at neutral pH. Histidine can occur in acidic pKa too

What happens when we titrate an amino acid? Titration curve indicates reaction of each functional group with hydrogen ion

Titration of alanine with NaOH At low pH – uncharged carboxyl group and positively charged amino group Alanine has a positive charge of 1 As base is added, carboxyl group loses proton – negatively charged carboxylate group and pH increases

Titration of alanine with NaOH Alanine has no net charge pH increases with addition of base – aminogroup loses it proton Alanine has negative charge of 1 Diprotic acid

What is Isoelectric point? Positive and negative charges are equal – no net charge – Isoelectric point or pH pI = pKa1 + pKa2 2 Determines properties of amino acids and proteins Molecules will not migrate in electric field. It can be at any pH

Which groups on amino acids react to form a peptide bond? Individual amino acids can be linked by forming covalent bonds PEPTIDE (amide) bond is formed between α carboxyl group of one amino acid and α amino group of another amino acid Dipeptide, tripeptide, polypeptide (> 100 amino acids)

Geometry of peptide bond The four atoms of a peptide bond joined by two alpha carbon atoms – lie in planar plane with bond angles of 120 about C and N Represented as a hybrid of two contributing structures – resonance structures Free rotation between the alpha carbon of given amino acid residue and amino nitrogen and carbonyl carbon of that residue. No rotation around peptide bond C and N. This constraint plays an important role in determining how the protein backbone can fold

What are some biological functions of small peptides? Marked physiological effects in organisms Naturally occurring dipeptide – carnosine is found in muscle tissue Glutathione – scavanger of oxidizing agents Oxytocin and vasopressin – hormones Enkephalins – naturally occurring painkillers Carnosine has alternative name – beta alanyl-L-histidine. Oxidizing agents causes lose of electrons, harmful to organisms, play a role in development of cancer

Carnosine Carnosine has alternative name – beta alanyl-L-histidine

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