Amino Acids

Time to get down to revising for my CHEM1004 exam!

I was originally going to do a series of posts going through textbook questions, but there were so many questions (plus so many that required diagrams) that after going through five or so chapters I realised that it wasn't an efficient use of my time. Besides, I'm sure my answers wouldn't have been that interesting to read either. Now I'm going to do the whole "expand on lecture key points" thing again because, let's face it, I have no imagination.

In this post, I'm going to talk about amino acids. To be honest, amino acids and proteins was probably my least favourite topic in this unit, but I guess it's pretty important because proteins have a wide variety of important functions in our bodies. So, without further ado, let's dig in:

Be able to draw the general structure of an amino acid in its cation, zwitterion and anion forms and know at which general pHs each form exists.

Amino acids can exist in a cation (positively charged), anion (negatively charged) or zwitterion (containing both positive and negative charges) forms. In the cation form, the amino group is positively charged (-NH3+) and the carboxyl group is neutral (-COOH). In the anion form, the amino group is neutral (-NH2) and the carboxyl group is negatively charged (-COO-). In the zwitterion form, the amino group is positively charged (-NH3+) and negatively charged (COO-).

Cation forms are more likely to exist at acidic pHs. This is due to the higher concentration of hydrogen ions which can protonate amino acids. The inverse is also true: anion forms are more likely to exist at basic pHs due to the lower concentration of hydrogen ions. Zwitterions are most commonly seen at around neutral pH.

Know that in all amino acids except glycine the α-carbon is a chiral centre and why this is the case.

In most amino acids, the amino carbon (i.e. the carbon next to the carboxyl group) is attached to four different groups: a hydrogen atom, the carboxyl group, the amino group and the amino acid side chain. Due to this, most amino acids are chiral. The exception is glycine as glycine's side chain is a single H. Thus the amino carbon of glycine has two identical -H side chains and is therefore achiral.

Understand the difference between R- and S- enantiomers and be able to identify the enantiomer given a structure of a chiral compound or be able to draw a structure given the enantiomer. This involves knowing the basis of priority for groups attached to the chiral carbon centre.

The first thing I'm going to attempt to quickly explain here is the concept of priorities (I'll probably cover this in further detail in a later post). Basically each chiral carbon atom is attached to four different groups. These groups can be given "priorities" for the purpose of determining whether the molecule is an R- or an S- enantiomer. Firstly, look at the four atoms directly attached to the chiral carbon and rank them in order of molecular weight (highest to lowest). So Cl would rank higher than O, O would rank higher than C, and so on. If you have a tie, take a look at the atoms attached to those atoms and go from there until you break the tie. (As I said, I'll probably explain this more clearly in a later post.)

Once you've assigned priorities to all four groups, mentally rotate the molecule so that the group with the lowest priority is facing away from you. If the other three groups are now going clockwise from highest to lowest priority, the molecule is in the R-enantiomer. If the three groups are going anticlockwise from highest to lowest priority, the molecule is in the S-enantiomer.

When it comes to drawing enantiomers, just be aware of your groups and their order, and make sure to place them accordingly. It makes it easier if you can draw them with the lowest priority atom already pointing away from you.

Understand that enantiomers rotate plane-polarised light either clockwise or anticlockwise by equal and opposite degrees and that this specific rotation, [α], is named dextrorotatory (D-, (+)) and laevoratatory (L-, (-)) respectively. Note that the direction of rotation cannot be predicted from the enantiomeric form of the chiral compound.

This dot-point kind of speaks for itself. Plane-polarised light, to my understanding, is basically like a long, flat beam of light. When it travels through optically active substances, the plane of light can rotate and this rotation can then be measured. Those that rotate the light clockwise are dextrorotatory and those that rotate the light anticlockwise are levorotatory.

Understand that most amino acids in biology are designated L-amino acids, but this does not refer to their specific rotation (some have (+) specific rotations some have (-) specific rotations), rather to their stereochemical relationship to L-glyceraldehyde. Know that most amino acids are thus S-enantiomers, except Cys that is R- and know why Cys is an exception. 

Once again, this dot point is kind of self-explanatory. After explaining what D- and L- means, I now have to take it back and say that that doesn't apply for amino acids. Instead, amino acids are designated as D- or L- depending on whether their structure is more similar to D-glyceraldehyde or L-glyceraldehyde. If you want to indicate specific rotation for amino acids, you'll have to stick to +/-.

Most amino acids are S-enantiomers (like L-glyceraldehyde), with -NH2 as their highest priority groups, followed by -COOH and then the amino acid side chain. Cysteine is an exception to this rule as its side chain is -CH2SH which ranks higher than -COOH due to the higher molecular weight of S compared to O.

Understand the importance of chirality in biology in relation to substrate binding in enzymes.

Chirality is important as different forms of the same molecule have different shapes, and enzymes will only bind substrates of the right shape. The wrong diastereomer, therefore, may not have any effect in a biological system.

Know which amino acids belong in each grouping and recognise the three-letter nomenclature for each amino acid. Know that Asp and Glu have carboxyl groups in their side chains, and the structures of the side chain groups of Lys, His and Arg. Also, know that Ser, Thr and Tyr all have –OH groups and that Cys has an –SH group.

I hate memorising stuff but apparently FAMILY VW is a good way to remember all of the hydrophobic amino acids. If only I could remember what each of the letters stood for...

Okay, well I remember that alanine is hydrophobic, so that must be the A. And then there's isoleucine, leucine and valine that are all also hydrophobic (the I, L and V). That's 50%! A pass (in Australia, at least)! w00t!

Hmm what else can I dig out of my brain... phenylalanine is hydrophobic, as it's basically just alanine attached to a benzyl (phenyl) group. (Just double-checked my book and it turns out that phenylalanine is F.) Also tryptophan is hydrophobic as that's a benzene ring attached to a five-carbon ring. Oh and then there's also proline, which is basically just a ring structure. Just one more...

Okay, stuff it, I'm just going to look in the textbook. Apparently the missing link is methionine, which I completely skipped over because I got fooled by the fact that it has an S in there (it's buried between two methyl groups, so it's probably not that reactive because of that).

Now for the other groups!

The polar acidic amino acids are aspartic acid and glutamic acid. Kind of easy to remember because there's only two of them and they both have "acid" in their names.

The three basic amino acids are lysine, histidine and arginine. Histidine has a five-membered imidazole ring in it (it's basically a ring with two Ns in it), arginine has two NH2 groups at the end, and lysine has a five-carbon chain (including the alpha carbon, not including the carbonyl carbon) with an -NH2 group at the end.

All other amino acids are polar uncharged. These are asparagine, cysteine, glutamine, glycine, serine, threonine and tyrosine.

Understand how polar and nonpolar amino acid side chains interact with water and how this influences their placement in a protein. Understand how hydrogen bonds are formed and be able to recognise potential H-bonding between amino acid side chains.

Water is relatively organised, with each water molecule hydrogen-bonded to other water molecules. When a hydrophobic nonpolar side chain enters the water, the water molecules have to rearrange to form a "cage" around it. This is energetically unfavourable, especially if there are a lot of hydrophobic chains exposed to the water. If all of the hydrophobic amino acids cluster together, however, with hydrophilic amino acids on the outside, this disruption of water molecules is reduced. Hence the outside of proteins tend to be hydrophilic with hydrophobic centres.

Hydrogen bonds are generally formed between relatively positive hydrogens and relatively negative oxygens or nitrogens. As there are plenty of =O and -NH groups in amino acids due to the peptide linkages, peptide chains can form intrachain hydrogen bonds. As well as in peptide linkages, certain amino acids (see my answer to the previous question) have groups such as -OH, -NH2 etc. which are also capable of forming hydrogen bonds. Hence hydrogen bonds can also form between amino acid side chains.