Amino Acids 20 common amino acids there are others found naturally but much less frequently Common structure for amino acid COOH, -NH2, H and R functional groups all attached to the a carbon

Ionization of amino acids

Amino Acid Basics pKa of the a amino and a carboxyl differ based on R group and microenvironment. See pg 79 and figures.

– The average is about 2.1 for the alpha carboxyl and 9.7 for the alpha amino groups - Amino acids are zwitterions - a molecule with both a pos and neg charge - All naturally occurring amino acids are optically active isomers, except glycine. L amino acids - R-groups determine the functionality of the amino acids.

All amino acids can be based on one of three basic groups, non-polar, uncharged polar and charged polar. Also are classified based on hydrophobicity, reactivity, acidic and basic nature, relative size of the side groups

The 20 Common Amino Acids You should know names, structures, pKa values for carboxyl and amino terminus, approximate pKa for ionizable groups, 3-letter designation (not single letter).

• Non-polar amino acids • Polar, uncharged amino acids • Hydrophobic/hydrophilic • Large steric bulky or small • Common reactions of amino acids • Unique features of unusual amino acids (Pro, Met, Cys…) • Acidic amino acids • Basic amino acids

Non-Polar Amino Acids Aliphatic, inert and non polar. These are very hydrophobic amino acids with various sized side groups.

Non-Polar Amino Acids

Aliphatic, inert and non polar. These are very hydrophobic amino acids with various sized side groups.

Non-Polar Amino Acids

Proline is the only aa where the alpha amino group is tied up in a ring structure. This amino acid is only slightly hydrophobic. The ring structure decreases the flexibility of the peptide backbone.

Polar Uncharged Amino Acids Hydrophilic (except Gly). Which of the side groups have potential for being involved in H bonding and salt bridges?

Polar Uncharged Amino Acids All are hydrophilic. Which of the side groups have potential for being involved in H bonding and salt bridges?

Acidic Amino Acids All are hydrophilic. Which of the side groups have potential for being involved in H bonding and salt bridges?

Basic Amino Acids

Less Common Amino Acids

Amino acids which rarely occur in proteins but are important for function

These amino acids are not synthesized by ribosomal processes; most typically arise from post-translational modifications to the protein, which are catalyzed by specific enzymes.

You are not responsible for knowing these amino acids, but should be aware they exist

SPECIAL CASES – CYSTEINE

Hydrophilic  amino  acid  contains  sulfur.  Cysteine  is  very  reactive  and  involved  in  the  structure  of  the  protein.    

Involved  in  disulfide  bonds  when  oxidized.

Side groups with -OH

Ser, Thr and Tyr -Only slightly hydrophilic. -The OH is only ionizable under very basic conditions. -The OH groups are very reactive and are phosphorylated similar to tyrosine. Phenylalanine, tyrosine and tryptophan All are aromatic rings. Pi bonds / e- clouds

create a very hydrophobic aa. Phenylalanine is very low in relative concentrations.

Trp and Tyr absorb at 280 nm. Peptide backbone absorb at 260 nm. These aa contain phenyl and indol rings.

Biologically important aa

Additional Reactions of Amino Acids Carboxyl groups form amides & esters Amino (e) groups of lysine forms Schiff bases Side chains show unique reactivities

• Cys residues can form disulfides and can be easily alkylated • Few reactions are specific to a single kind of side chain

More titrations When the amino acid is has a 0 net charge that is considered the isoelectric point. For amino acids with side groups that contain an ionizable moiety it is the average of the two pKa that are charged when the net charge is zero.

Isoelectric Points If the side group is not ionizable, then the pI is the average of the C and N groups pKa Calculations of pI for a compound with more than two dissociable groups carries more possibility for error First write out all possible ionic structures for a compound in order that they occur starting with the most basic to the most acidic Next, identify the isoionic, zwiterionic or neutral representation

- The pI is the pH at the midpoint between the pK values on either side of the isoionic species

What about peptides or proteins?

“Peptides”

Peptide formation is the creation of an amide bond between the carboxyl group of one amino acid and the amino group of another amino acid.

Short polymers of amino acids Each unit is called a residue 2 residues - dipeptide 3 residues - tripeptide 12-20 residues - oligopeptide many - polypeptide Each amino acid is called a residue

Addition of acid or base hydrolyzes the peptide bond and adds water back across the peptide bond.

The amino (N) terminal is written on the left and the carboxyl (C) terminal is on the right.

Peptide Bond – Rx of bond formation costs energy (ATP) but degradation of proteins is thermodynamically

favorable. (entropy) – C-N bond shorter than normal and more like double bond – This results in rigid planar, non-rotating links between aa – Size of peptides and proteins are described in Daltons – 1 atomic unit = 1 dalton ; MW = Dalton / kd; Mr=molecular weight

Peptide Bond

• is usually found in the trans conformation • has partial (40%) double bond character • N partially positive; O partially negative • has a length of about 0.133 nm - shorter than a typical single bond but longer than a double bond • Due to the double-bond character of the peptide bond, the six atoms of the peptide bond group define a

plane – the amide plane

The Peptide Bond

The peptide bond has partial double bond character. One of the postulated resonance forms is shown here.

Many peptides have important biological activities Biologically important peptides Insulin -

– Short peptide produced as a pre-pro-peptide. The initial peptide is much longer and is modified twice, each time a set of peptide bonds are hydrolyzed. The final shortened version is active. There are two subunits, held together by a disulfide bond.

Bioactive Peptides

Oxytocin and Vasopressin – Start as long precursors in hypothalamus- whose final form is 9 aa – differ by 2 residues

• oxytocin - uterine contraction during childbirth and milk production during lactation • vasopressin - alters blood pressure by forcing kidney to retain water, increasing the

volume of blood Met-enkephalin (opioid peptides)

» Naturally produced peptides, bind to receptors, and reduce pain cause pleasure. Morphine like

Substance P » Opposite effect from opioids » Stimulates perception of pain (protective mechanism)

“Protein” One or more polypeptide chains

One polypeptide chain - a monomeric protein More than one - multimeric protein Homomultimer - one kind of chain Heteromultimer - two or more different chains Hemoglobin, for example, is a heterotetramer It has two alpha chains and two beta chains

Proteins - Large and Small Insulin - A chain of 21 residues, B chain of 30 residues -total mol. wt. of 5,733 Glutamine synthetase - 12 subunits of 468 residues each - total mol. wt. of 600,000 α−Connectin (a muscle protein) - MW 2.8 million β−Connectin - MW of 2.1 million, with a length of 1000 nm - it can stretch to 3000 nm

The Sequence of Amino Acids in a Protein Is a unique characteristic of every protein Is encoded by the nucleotide sequence of DNA Is thus a form of genetic information Is read from the amino terminus to the carboxyl terminus