Introduction to Molecular and Cell Biology, Biol. 220 Lecture 3: Amino Acids
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The 20 naturally occurring amino acids are built on a common theme.
A free amino acid has the general structure shown in Fig. 1 with an amino group, NH2, at one end and a carboxyl group, COOH, at the other.

  Fig. 1 Elementary Amino Acid Structure

 Each goup is attached to an alpha carbon.  Also attached to the alpha carbon is a H atom and an R group (side chain) (Fig. 1).  The R group is the only thing that varies from one amino acid to another. In an aqueous solution at a neutral pH, amino acids do not exists as shown in figure 1 (Fig. 1), but tak on a charged nature as shown in figure 2. (Fig. 2). When a molecule has both a positive and negative charge it is called a zwitterion.

 

Fig. 2 Amino Acids Act as Zwitterions When in Solution

 

Since the central alpha carbon is asymmetrical there are two possible isomers which are mirror images of each other (Fig. 3)  Biological systems use the L isomer.

 

Fig. 3 Isomeric forms of Amino Acids

 

When amino acids are dissolved in water, the amino and carboxyl groups act as bases and acids respectively as shown in Fig. 4.  Therefore, amino acids are considered to be Zwitterionic (possessing both - and + charge) and amphoteric (able to act as an acid or as a base)

 

Fig. 4 Titration of Amino Acid with Base

pH is a measure of the free H+ ion concentration in a solution (pH = -log[H+].

Acids contribute H+ ions to a solution: HA -> H+  + A-.

Bases take up H+ ions from a solution: B + H+ -> BH+.

Amino acids can act as buffers (resistant to pH change) in a pH range which is + or - 1 pH unit from their pKa values (pKa = -log Keq for acid dissociation).

The point on a titration curve, as shown in Fig. 4, where the amino acid has an equal number of positive and negative charges called the isolelectric point because such molecules when placed in an electric field will be unable to migrate to either the anode or cathode.  The pH at which the isolelectric point occurs is called the pI.

 

Q: What would the charges be on an amino acid at pH = 1, or pH = 12?

 

 

Functional Grouping
Just twenty different amino acids are used to synthesize proteins. They can be described by 3 letter abbreviations or 1 letter abbreviations and are distinguished by the nature of their R-groups (Table 1).

Table 1 Click on the name of the Amino Acid to see an interactive 3-D view of each amino acid. (Note: to view this interactively on your Web browser, the free Chemscape Chime plug-in viewer must be installed in your browser's plug-in folder.)

Name	Abbr.	Abbr.	Structure
Non-polar	.	.	.
Glycine	Gly	G
Alanine	Ala	A
Valine	Val	V
Leucine	Leu	L
Isoleucine	Ile	I
Proline	Pro	P
Cysteine	Cys	C
Methionine	Met	M
Phenylalanine	Phe	F
Tryptophan	Trp	W
Polar	.	.	.
Serine	Ser	S
Threonine	Thr	T
Tyrosine	Tyr	Y
Asparagine	A	N
Glutamine	Gln	Q
Basic	.	.	.
Lysine	Lys	K
Arginine	Arg	R
Histidine	His	H
Acidic	.	.	.
Aspartic Acid	Asp	D
Glutamic Acid	Glu	E

Amino acids fall into four groups:

NON-POLAR NEUTRAL

 The NON-POLAR NEUTRAL amino acids are HYDROPHOBIC (water-repelling).

There are 10 amino acids with hydrophobic side chains. They tend to interact with one another and with other hydrophobic groups and would be expected to be located within the interior of a protein or in membranes. Typically they have primarily C and Hs in the R group.

 The simplest of course is glycine, which has a single H as its side group:

 alanine, valine, leucine, and isoleucine have hydrocarbon chains consisting of up to 4 carbon atoms.

 Proline also contains a hydrocarbon side chain but it forms a ringed structure:
As a result, a proline residue disrupts the usual organization of the backbone of a polypeptide chain, causing a sharp transition in the direction of the chain. The presence of proline, therefore, interrupts the formation of any regular repeating structure.

 The side chains of cysteine and methionine contain sulfur atoms. Methionine is very hydrophobic, cysteine is less so.  Even though both contain sulfur atoms, only cysteine can form disulfide bonds.

 Phenylalanine and tryptophan both have side chains containing very hydrophobic aromatic rings.  These amino acids can participate in ring stacking.

BASIC

 Three amino acids have basic R-groups:
  lysine, arginine, and histidine

 Addition of a hydrogen ion converts the free (second) amino group of lysine or arginine to the positively charged form NH3+. A proton can similarly be added to the histidine ring making it positively charged.

Important point: charge of the side group will depend upon the pH of the surrounding solution.

 Lysine and arginine exist in the + charged form within the cell  (pH 6-8).

 Histidine can be either uncharged or charged at physiological pH so it frequently plays an active role in enzymatic reactions involving the exchange of H ions.

 The basic amino acids are polar and hydrophilic and, therefore, would normally be found on the outer surface of a protein.

 Two amino acids have acidic R-groups: aspartic acid and glutamic acid.

 Because the R-group carboxyl  can lose a hydrogen ion to exist in the negatively charged form O=C-O-. Both exist in - charged form within the cell. These amino acids are also polar and hydrophilic and, therefore, would be found on the outer surface of a protein.

 Five amino acids are classified as POLAR Like the basic and acidic amino acids, the polar amino acids are hydrophilic and able to hydrogen bond with water.

Three are considered alcohols and have OH groups in their side chains: serine, threonine, and tyrosine.

 Two have polar amide groups [ O=C-NH2]: asparagine and glutamine. The amide bonds are very similar to those found in peptide bonds.

In addition to the standard 20 amino acids, certain others are occasionally found in proteins. They are created by modifying one of the standard amino acids after it has been incorporated into the protein.

Q: Which amino acid R-groups are able to participate in: 1) H-bonding, 2) Hydrophobic interactions, 3) Disulfide bonding, 4) Ring stacking, 5) Ionic bonding, 6) van der Waals interactions?

 Amino acids are joined together to form a protein through the formation of peptide bonds between amino acids.

 Peptide bonds are created by the condensation of the carboxyl (COO^-) group of one amino acid with the amino (NH₃⁺) group of the next (Fig. 6). Condensation involves the removal of one water molecule.

Fig. 6Peptide bonds are formed by condensation between the amino and carboxyl groups.

 

Since peptide bonds are covalent, they are relatively stable, and in the living cell are broken only rarely, usually as the result of a specific enzymatic action. Peptide bonds are broken in a process which is functionally the opposite of the condensation reaction. This process involves the addition of H₂O and is termed hydrolysis (Fig. 7).

Fig. 7 Peptide bonds are broken by hydrolysis.

 

Electrons are shared by the O,C, & N atoms in such a way the bond has a stiffness which resists rotation. As a result, each peptide bond lies in a flat plane (Fig. 8).

Fig. 8 Peptide plane.

 

Rotations must occur at the alpha carbon around the Phi and Psi bonds (Fig. 9).

Fig. 9 Polypeptide

 A peptide consisits of a small number of amino acids connected by peptide bonds.  These form an articulated chain of flat plates (Fig. 9).

 A longer chain of amino acids joined in this manner is called a polypeptide.

 We can define the direction of a polypeptide chain according to the orientation of the peptide bonds. The amino acid at one end of the chain must have a free NH2 group and thus defines the amino- or N terminal end (Fig. 9).

 The amino acid at the other end must have a free COOH group and thus defines the carboxy- or C terminal end (Fig. 9).

 Protein sequences are conventionally written from N-terminus (at the left) to C-terminus (at the right).

 The peptide bonds form a zig-zag backbone, from which the side-groups (denoted R) protrude (Fig. 10). The R group is different for each amino acid and determines the nature of its contribution to the overall protein structure.

Fig. 10 Orientation of R-groups and Peptide Planes

 

Q: Are all combination of psi and phi angles possible?

 

 

Polypeptide Conformation

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The angle conformations of the bonds around the alpha carbon are critical in determining the structure of the polypeptide and ultimately its function (Fig. 10).

Bonds

The bond between the alpha-carbon and the nitrogen of the peptide bond assumes an angle called Phi.  This angle can range from -180 to 180 degrees.

The bond between the slpha-carbon and the carbon attached to the oxygen in the peptide plane assumes an angle called Psi.  This angle can also range from -180 to 180 degrees.

When each of these angles are set to 0, the peptide planes are oriented as shown in Fig. 11.  Notice that you are looking down the plane which includes the alpha-carbon, the H and the R-group.

Fig. 11 Phi and Psi bond angles of 0.

Angle Combinations

The conformation of the phi and psi angles shown in Fig. 11 obviously does not exist because of the steric hinderance between the H and O groups from the adjacent planes.  When angles of phi and psi are monitored in natural polypeptides and proteins, it is found that these two angles tend to be restricted to certain combinations of angles.  Fig. 12 shows a plot of the phi and psi angles from over 300 residues naturally occuring in polypeptides.
 Fig. 12 Plot of Phi and Psi angle conformations for 386 phenylalanines from 52 proteins.

Summary:

Even though the peptide planes have the potential to assume any angle around the alpha carbon, they do not because certain combinations of Phi and Psi angles

 

   Quiz 3

 

Created 2004 by CA Rinehart• email CA Rinehart

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