Amino Acids

The Amino Acids

Why is memorizing the amino acids a traditional biochemistry rite of passage?

It's because their chemistry is part of the vocabulary of biochemistry. When I write "YWFVLIV" you need to recognize a peptide that is highly hydrophobic, absorbs UV light, and has a side chain pKa around 10. The reason I spend lecture time on the amino acids is to give you a sense of their "personalities."

Here is the common structure of the amino acids (formally, alpha-amino carboxylic acids):

So...what do you need to know about each amino acid?

The common structure of all the amino acids. I don't require memorization of the sterochemistry shown in the figure, but you should appreciate that the existence of a unique stereochemistry is vital to biochemistry, since otherwise a typical 100-residue protein would exist as a mixture of 2^100 diastereomers.
Is the amino acid large hydrophobic, small hydrophobic, polar, or charged? You don't need to remember the molecular formula or molecular weight.
What is the structure of the side chain? The most important aspect of the side chain is the functional group, if any. I am more willing to forgive making a mistake on the number of methylene groups in a side chain.
If there is an ionizable side chain, what is its approximate pKa? What is the dominant prototropic form at any given pH? You need not memorize the precise pKa's of the NH2 and COOH groups.
Does it absorb UV light?
And, of course, the name, 3-letter abbreviation, and one-letter code

Notes on individual amino acids:

I am not going to reproduce table 4-1 of V-V-P. These are just added comments I made in class.

Small Hydrophobic Amino Acids
Glycine Gly G		The smallest and most flexible amino acid. Tends to be a structure breaker because of the entropy cost of restraining its flexibility. The only achiral amino acid.
Alanine Ala A		The John Q. Public of amino acids. When molecular biologists want to know where important amino acids are, they can "alanine scan," replacing each amino acid in turn to look for functional effects.
Large Hydrophobic Amino Acids
Valine Val V		Branched at C-beta: the carbons are identified by Greek letters as shown. Hydrophobic, therefore side chain tends to pack inside the protein. Discrimination between valine and isoleucine is a challenge for the translational machinery, as they differ by one methyl group. Valine can fit anywhere Ile can. To aminoacylata tRNAIle specifically, a separate smaller active site removes mis-added valine.
Leucine Leu L		Branched at C-gamma. The classic large hydrophobic. The most common amino acid. "Leucine zipper" transcription factors have a series of leucines (every seventh residue) lined up on one face of an alpha helix that forms part of an interface to another subunit, forming a dimer.
Isoleucine Ile I		Chiral at C-beta (don't worry about the configuration). See valine above.
Methionine Met M		One of two sulfur-containing amino acids, the other being Cys. They are useful for radioactively labeling proteins, for example in in vitro transcription-translation systems. Formyl-Met is the N-terminal amino acid during protein synthesis, though it is often cleaved off. Rare.
Proline Pro P		Cyclic, rigid ring structure. Strictly not an amino acid, often called an imino acid. The lack of a hydrogen on the N (after incorporation into a peptide) means that it cannot form the H-binds seen in extended structures, therefore acts as a structure breaker. The only amino acid that can exist significantly with a cis- peptide bond.
Phenylalanine Phe F		Mnemonic _F_ennelalanine. One of three aromatic amino acids, therefore absorbs UV light, although not as weell as Tyr or Trp. Hydroxylated to form tyrosine. If this pathway is defective, phenylketonuria or PKU results. This was the first genetic disease of metabolism whose molecular mechanism was understood. Aspartame is half Phe, PKU sufferers must avoid it.
Tryptophan Trp W		Aromatic. Largest and rarest amino acid. Mnemonic is W for wide, or for you New Jersey residents it's "Twp," the abbreviation for townships. Absorbs furthest into the red (at 280 nm, in the UV), therefore often added to designed proteins as a convenient spectroscopic handle.
Polar Amino Acids
Serine Ser S		The only amino acid with a primary hydroxyl, often seen as a nucleophile in enzyme active sites. Can act as a hydrogen bond donor or acceptor. Can be phosphorylated, the most commonly phosphorylated amino acid.
Threonine Thr T		The only amino acid with a secondary hydroxyl. Chiral C-beta. Can be phosphorylated, though less frequently than Ser.
Asparagine Asn N		Amide functional group can act as a donor and acceptor of hydrogen bonds. Can be hydrolyzed during workup, and then becomes Asp. If the identity is uncertain, the amono acid is denoted Asx (abbreviation B).
Glutamine Gln Q		Similar to Asn but one methylene group longer. Can be hydrolyzed during workup, and then becomes Glu. If the identity is uncertain, the amono acid is denoted Glx (Z). The main control point for assimilation of nitrogen from the environment.
Cysteine Cys C		The other sulfur-containing amino acid. Two Cys's can be reversibly oxidized to form the disulfide crosslink shown. Disulfides are typically extracellular, as in insulin and antibodies. Also can act as a nucleophile, with a sulfhydryl side-chain pKa of about 8.4, giving thiolate anion (S^-) upon deprotonation.
Tyrosine Tyr Y		Mnemonic tYrosine. Phenylalanine plus a hydroxyl. Side chain pK_a of about 10.5 fo rthe indicated form, meaning it's usually neutral. Tyrosine can be a nucleophile (as in DNA topoisomerases), can be phosphorylated. Tyr phosphorylation is rare, but critical in cellular responses to extracellular stimuli.
Charged Amino Acids
Lysine Lys K		Mnemonic: K is before L. Lysine has a primary amino group. A pK_a of around 10.5 for the protonated form shown means that for practical purposes it is nearly always positively charged. Often found interacting with nucleic acids. The amine can be reacted with carboxylates to form an isopepttide linkage, as seen with the conjugation of the small protein ubiquitin to its targets, which marks them for degradation by the proteasome.
Arginine Arg R		Mneomonioc aRrrrgh. Arginine is the most basic amino acid, with a side-chain pK_a for the guanidinium group of about 12.5. Positive charge is extensively delocalized as shown. Can donate several H-bonds, often seen in protein-nucleic acid interaction.
Histidine His H		Histidine is the only amino acid with a pKa in the physiological range, hence often seen in active sites when donation or abstraction of a proton is needed. The protonated form shown has a pK_a around 6 for the indicated proton , meaning it's mainly neutral at pH 7.
Aspartate (aspartic acid) Asp D		Mnemonic "aspardic" acid. Side chain pK_a of about 4. Part of Aspartame. One of two negatively charged amino acids.
Glutamate (glutamic acid) Glu E		Mnemonic one letter larger than D. Side chain pK_a of about 4. Neurotransmitter. Monosodium glutamate is a flavor enhancer -- MSG is the "fifth flavor," after sweet, sour, bitter, and salty.