What Are Amino Acids?• Amino acids are building blocks for proteins – They have a central α‐carbon and α‐amino and α‐carboxyl groups – 20 different amino acids – Same core structure, but different side group (R) – The α‐C is chiral (except glycine); proteins contain only L‐isoforms. • Amino acids are ampholytes: – pKa of α‐COOH is ~2 – pKa of α‐NH2 is ~ 9• At physiological pH most amino acids behave as zwitterion.
Amino Acids Classification• Amino acids can be classified according to POLARITY to: – Hydrophobic / non‐polar R group: Glycine, alanine, valine, leucine, isoleucine, methionine, proline, phenylalanine, tryptophan – Polar R group (net charge 0 at pH 7.4): Serine, threonine, cysteine, tyrosine, asparagine, glutamine, histidine – Polar R group (Charged ion at pH 7.4): aspartate, glutamate, lysine, arginine
Non Polar R‐ Group O O C O- +H3N CH C O- CH3 +H2N Proline alanine O O O +H3N CH C O- +H3N CH C O-+H3N CH C O- CH2 CH CH3 CH CH3 CH CH3 CH2 CH3 CH3 CH3 valine leucine isoleucine
Non Polar R‐ Group O O +H3N CH C O-+H3N CH C O- CH2 CH2 CH2 O S HN +H3N CH C O- CH3 CH2 Methionine Tryptophan Phenylalanine
O Polar R‐ Group +H3N CH C O- O O +H3N CH C O- CH2 +H3N CH C O- CH OH CH2 CH2 C O CH3 threonine serine glutamine O NH2 OH +H3N CH C O- CH2 O +H3N CH C O- O +H3N CH C O- CH2 CH2 SH O tyrosine OH C O +H3N CH C O- cysteine NH2 Hasparagine Glycine
O OCharged R‐ Groups +H3N CH C O- +H3N CH C O- CH2 CH2 O CH2 CH2+H3N CH C O- lysine CH2 CH2 CH2 arginine C O CH2 NH O- O NH3+ C NH2+aspartatic acid +H3N CH C O- NH2 CH2 CH2 C O glutamic acid O-
Amino Acids Classification• Amino acids can be classified according to R‐ Group to: – Aliphatic: gly (G), ala (A) , val (V), leu (L), ile (I) – Aromatic: Trp (W), Phe (F), Tyr (Y), His (H), – Sulphur : Met (M), Cys (C) – Hydroxyl: Ser (S), Thr (T), Tyr (Y) – Cyclic: pro (P) – Carboxyl: asp (D), glu (E) – Amine: lys (K), arg (R) – Amide: asn (N), gln (Q)
Aliphatic Side‐Chain Amino Acids O O +H3N CH C O- +H3N CH C O- H CH3 glycine alanine O O O +H3N CH C O- +H3N CH C O-+H3N CH C O- CH2 CH CH3 CH CH3 CH CH3 CH2 CH3 CH3 CH3 valine leucine isoleucine
Hydroxy‐Containing Amino Acids O O +H3N CH C O- +H3N CH C O- CH2 CH OH OH CH3 serine threonineSulfur‐Containing Amino Acids O O +H3N CH C O- +H3N CH C O- CH2 CH2 CH2 SH S cysteine methionine CH3
Acidic Amino Acids O O +H3N CH C O- +H3N CH C O- CH2 CH2 C O CH2 O- aspartatic acid C O glutamic acid O-Amides of Acidic Amino Acids O O +H3N CH C O- +H3N CH C O- CH2 CH2 C O CH2 C O NH2 asparagine NH2 glutamine
Basic Amino Acids O O +H3N CH C O- +H3N CH C O- CH2 CH2 CH2 CH2 CH2 CH2 CH2 NH NH3+ C NH2+ NH2 lysine arginine
Benzene‐Containing Amino Acids O O +H3N CH C O- +H3N CH C O- CH2 CH2 OH phenylalanine tyrosine
Heterocyclic Amino Acids O O O +H3N CH C O- +H3N CH C O- C O- CH2 CH2 +H2N N NH HN Proline histidine tryptophan
Learn Amino Acids Structures• The best approach is to use logic and name recognition and to look for similarities, not differences in structures.• The Name should tell you the structure.• Structures are built on one another and interrelate. • Learning amino acids prepares you for understanding proteins structure.
BASICS Lets start with the basics. All amino acids have a common structural unit that is built around the alpha carbon (click 1). Lets call this the “core” structure. The figure shows the core with one of the bonds on the ‐carbon unassigned. A group in this location is represented by the letter R (click 1). COOH +H 3N C H R RR groups are the only variable groups in the structure. Consider R the only unknown and focus on this group to learn the structures. Hence, Rule (1) is amino acids are composed of a core group and an R group. Rule (2) is the R group gives an amino acid its structural identity and, later as we will see, its unique biochemical properties. Thus, if you insist on using flash cards, draw them as shown above (click 1) with the box representing the core. Click to go on.
Building an R Group You saw the importance of the R group. Now, you will see how R groups build and interrelate. Four that illustrate this point are “glycine, alanine, phenylalanine and tyrosine. The R groups of each will be shown below (click 1). Glycine Alanine Phenylalanine Tyrosine H CH3 CH2 CH2 OH With an H, glycine is the simplest amino acid, so named because of its sugary taste (click 1). Alanine with a methyl group is the next simplest (click 1). The red color helps you see how each R group structure differs from the preceding. Phenylalanine arises when a phenyl group replaces an H on alanine’s methyl group (click 1). Tyrosine evolves by adding an –OH group to the para position on the phenyl ring of phenylalanine (click 1). Click to go on.
Acidic and Amide Amino Acids The acidic amino acids have (–) charges in their R group. There are two, aspartic acid and glutamic acid (click 1). Note their similarity. Glutamic acid has one more –CH2 group (click 1). Note that both have a –COO– group which gives the negative charge. Aspartic Glutamic Asparagine Glutamine acid Acid CH2 CH2 CH2 CH2 COO– CH2 COO– C=O CH2 COO– NH2 C=O COO– Aspartate Glutamate NH2The –COO– can exchange a proton with the solvent and hence behave as an acid. The suffix “ate” is used to designate an ionized acid (more properly called a salt). Hence, you will see aspartic acid and glutamic acid referred to as “aspartate” and “glutamate” (click 1). By forming the amide derivatives of aspartate and glutamate you give rise to asparagine and glutamine (click 1). Note name and structure similarities between the “open” and the corresponding “amide” amino acids. Click to go on.
The (+) charged amino acids are represented by lysine, arginine and histidine. Unfortunately, R structures for basic amino acids have little resemblance to one another. But each is characterized by a (+) N in the R group. Lysine Arginine Histidine CH2 CH2 CH2 CH2 CH2 CH2 CH2 HN NH+ CH2 NH +H Imidazole NH3+ 2N=C NH2 Epsilon amino GuanidiniumIt will help you to remember that each (+) N is part of a group. For lysine this group is called the epsilon amino group (click 1). In arginine it’s the guanidinium group and for histidine it’s the imidazole group. Remember these group names and you will remember the structures of the basic amino acids. Click to go on.
Serine,Threonine, Cysteine and Methionine Start with serine. Serine has a simple –CH2OH for it R group (click 1). Threonine is serine with a methyl group (click 1). And, if you replace the O in serine with an S, you generate cysteine (click 1). Serine Threonine Cysteine Methionine CH2OH H‐C‐OH CH2SH CH2 CH3 CH2 S CH3 Methionine appears to combine cysteine with threonine. The name tells you methionine has a sulfur (thio) and a methyl group in the structure. Like threonine methionine has a 2 carbon chain attached to the alpha carbon (click 1). This is followed by sulfur and ends with a methyl on the sulfur. Click to go on.
Valine, Leucine, Isoleucine These 3 branched‐chain hydrophobic amino acids have only C and H in their R groups. Valine is easy to remember because the carbon chain is arranged as the letter V (click 1). Leucine and isoleucine both have a 4 carbon R group. Leucine resembles valine but with a ‐CH2 before the V (click 1). Isoleucine’s side chain resembles the letter L, just the opposite of what you would predict from the name (click 1). To distinguish the 3, focus only on the branched chains in the R structure. Valine and leucine have only methyl groups, whereas isoleucine’s branches are one methyl and one ethyl group (click 1). Click to go on. Leucine Isoleucine Valine C C C– C C C C C Ethyl group C C C
Tryptophan and Proline The last 2 amino acid to consider are tryptophan (pronounced trip‐toe‐fane) and proline. Tryptophan is unique in having an indole ring (click 1). Attach this ring to the core via a CH2 group and you complete the structure of tryptophan (click 1). Proline also has a ring, but this ring is saturated. In fact proline’s ring looks like “home plate” in baseball (click 1). Note proline does not have a core structure. This is because the alpha amino group is incorporated into the ring. Tryptophan Proline H2C CH2 CH2 H H2C C N COO– N H H Indole This completes all the amino acids. Review this lesson as many times as necessary. Use paper and pencil to draw out the structures. Soon you will have mastered amino acid structures. Click to go on to quiz.
Test Your Knowledge. Click to see the answer.Q: What amino acid has the shortest carbon chain in its R group? A.Q: What structural feature is common to alanine, serine and cysteine? A:Q: Which amino acid has the longest straight chain of carbons in its R group? A:Q: What R group structural feature is common to phenylalanine, tyrosine, tryptophan, and histidine? A:Q: What structural feature is common to isoleucine and threonine A: