Tiempo de lectura: 13 minutos

The foundations of biochemistry are biomolecules. Learning the role that carbohydrates, lipids, nucleic acids and proteins play in our cells is what elucidates how the body words. According to the interactions between these polymers, we are able to understand a variety of processes, from energy storage to mechanisms of fighting against disease! Despite the relative importance of each of the biomolecules mentioned here, proteins occupy a place of honor in the molecular hierarchy, especially in biochemistry. They catalyse reactions, like ATP synthesis, serve as receptors, adhere cells together, form structures such as keratin (in hair) and collagen (in skin), etc. The immense range of functions that proteins can perform depends mainly their structure. And yet, only 20 amino acids make up our VIPs (very important proteins).

In this article I will discuss how it is possible that only 20 amino acids can yield the wide variety of structures and the characteristics that tie them together. For those of you who are already familiar with these monomers, there will also be fun facts dispersed throughout, so I’m sure there will be something new for everyone.

20 known amino acids

Amino acids are relatively small molecules, ranging from 10 to 27 atoms in size. Their name comes from the functional groups they present, as they contain both an amino group (-NH_{2}) and a carboxylic acid group (-COOH).

The R stands for any other atom or chain of atoms that will form the side chain. This is what varies depending on the amino acid and what will be the key to understanding how only 20 molecules can assemble into all the different types of protein.

Normally, because amino acids are in aqueous environments, these structures exist with a positive charge on the amino group and a negative charge in the carboxyl group. This form is called «zwitterion», from the German word «Zwitter», meaning hermaphrodite.

Amino acid side chains

Before analysing all of the side chains, I would like to point out some of my favorite resources as a student to learn about amino acids. The first is the table from Compound Chem found below and the second is a poem by LeRoy Kuehl, a Biochemistry professor from the University of Utah, titled «Amino Acid Tales». These two different explanations of the properties of amino acids (one very straightforward and condensed, the other more comedic and poetic), provide options for different learning styles. I hope that this article will also serve as a reference for studying them.

Glycine

The smallest and simplest of them all. Glycine has R=H so it is not chiral like the other 19 amino acids. Chirality occurs when a carbon is bonded to 4 different groups and it causes special features that we will see later on.

Glycine is perfect for providing flexibility in a chain because of its size, which is why spider silk is made up of around 42% glycine residues. Since it only has a hydrogen atom for a side chain, it is able to pack closely together, forming strong, yet flexible filaments. In turns of proteins that link alpha helices or beta sheets together, there is also an abundance of glycine.

Alanine and Valine

Alanine has R=CH_¨¨{3}, so it is only one methyl group different from glycine. However, because of the change it is now a chiral molecule. This feature causes the appearance of two enantiomers: molecules that have the same formula but are mirror images of each other. We know that they are not the same molecule because one of them will rotate polarised light in one direction, while the mirror image one will rotate polarised light in the opposite direction. Although this seems silly, the spatial orientation of the groups attached to a chiral carbon can have significant implications. For example, the smell of lemon and the smell of orange arise from limonene. However, S-limonene smells like lemon and R-limonene smells like orange.

Valine has R=CH_2CH_3CH_3 in the form of a «V». This is the first of the amino acids that we have discussed so far that is essential for the human diet. All amino acids are necessary for a balanced nutrition, but essential amino acids cannot be produced by the body from other components.

Leucine and Isoleucine

These are isomers of each other, so both of their R=CH_2CH_2CH_3CH_3. However, the way in which these groups are organised cause the differences between them. Because of this, isoleucine has two chiral centers, instead of one like leucine.

Combined with valine, leucine and isoleucine make up the branched-chain amino acids (BCAA’s). There are several rare genetic diseases linked to a malfunction or deficiency in proteins that can break these amino acids down, restricting the individual from eating them in a regular diet. One such condition is called maple syrup urine syndrome. Due to accumulation of these molecules and their toxic derivatives, they can produce neurological dysfunction, lethargy and irritability. It is diagnosed within the first 24-48 hours of life.

Proline

This is the last aliphatic amino acid, with R=NHCH_{2}CH_{2}CH_{2}. Aliphatic means that it is made up of hydrocarbon chains and no hydrocarbon rings. Compounds which exhibit hydrocarbon rings are called aromatic and they will be covered next.

Despite being on the list of amino acids, proline is actually an imino acid. Another curiosity of this molecule is that its side chain is linked to the backbone through the nitrogen ring. Since the amino group is no longer able to form hydrogen bonds because of how it is held in the ring, proline serves to interrupt secondary protein structures, mainly those of alpha helices.

Furthermore, proline was synthesised in vitro one year before it was isolated in nature (1901)! Both the scientist who prepared the synthetic reaction, Richard M. Willstätter, and the one who isolated proline in nature, Emil Fischer, won Nobel Prizes in Chemistry! Dr. Willstätter was awarded for investigating plant pigments and Dr. Fischer received the prize for developing the Fischer synthesis.

Richard Willstätter
Emil Fischer

Phenylalanine

This amino acid has R=CH_{2}C_{6}H_{5}. The ring it contains as a side chain is called a benzene ring. All compounds which contain these kinds of species are called aromatic because of their fragrant properties.

Similar to valine, leucine and isoleucine, phenylalanine is also an essential amino acid. It is a precursor of tyrosine (see below) and it is involved in a pathway to synthesize L-dopa, which is in turn the precursor of dopamine. Through this pathway it is also possible to obtain epinephrine and norepinephrine, the hormones of fight and flight, respectively.

Tryptophan

Next is the largest amino acid, at 27 atoms, whose R=CH_2C_8H_7N. The bicyclic system it contains at the end is called an indole group.

A fun fact about this amino acid is that it can absorb light at 280nm, which corresponds to UV light. The only other amino acid which can do this is tyrosine, but tryptophan is responsible for most of the absorbance at this wavelength. This is useful because it the measure of absorbance can be used to determine the concentration of a protein in a sample.

Tryptophan is thought to be linked to sleepiness when consumed in large quantities. That is why turkey, a food eaten during Thanksgiving which is rich in tryptophan (usually eaten during Thanksgiving), causes lethargy.

Additionally, tryptophan is a precursor for serotonin! It really does a lot in the body.

Tyrosine, Serine and Threonine

These three amino acids contain hydroxyl groups, which makes them slightly or very polar. Tyrosine is phenylalanine with a hydroxyl group appended, so its R=CH_{2}C_{6}H_{5}OH. Serine is much smaller and it is like alanine with a hydroxyl group appended, so its R=CH_3OH. Last in this sequence, threonine contains an extra carbon with respect to serine, so R={CH_3CH_2OH}, granting an additional chiral center.

Methionine and Cysteine

These are the only two amino acids which contain sulfur. For methionine, R=CH_2CH_2SCH_3 and for cysteine R=CH_2SH. You might ask yourself why these amino acids contain such a large atom and the reason is that sulfur has very interesting properties for proteins.

Sulfur has the ability to make disulfide bonds. These are crucial for the structure of antibodies and other larger proteins. Disulfide bonds are a kind of ionic interaction that forms exclusively from cysteines. A very famous experiment that proved that proteins always adopt the lowest energy conformation depended on these disulfide bonds. Christian Anfinsen, another Nobel Prize winner, concluded that the information required for a protein to fold into its native structure is contained exclusively within its sequence of amino acids.

Methionine, on the other hand, is the first amino acid in every protein. Do not alarm, it can be cleaved during post-translational modifications, but the start codon of an mRNA will always be AUG, which codes for methionine. The reason for this is not entirely known, but it happens in all eukaryotes.

Aspartic acid and Glutamic acid

These are the acidic amino acids. As we saw at the start, all of the amino acids contain an acidic group, but these contain two. For aspartic acid, R=CH_2COO^- and for glutamic acid, R=CH_2CH_2COO^-.

Aspartic acid is involved in several pathways, but most importantly in the urea cycle. Combined with ammonia, it donates the amino groups which lead to the formation of urea. Furthermore, it is of economic interest for its superabsorbent properties. Both diapers and feminine hygiene products rely on polyaspartic acid for their functions and this chemical is biodegradable, unlike its counterpart polyacrylate.

Glutamic acid, also known as glutamate, is probably in your spice cabinet right now. Monosodium glutamate (MSG) is a flavor enhancer that is present in a wide variety of foods. It is said that this compound is also responsible for the umami flavor, the one triggered by artichokes for example.

Asparagine and Glutamine

These are the amidic amino acids. As you may have noticed, they have the same root names as above, but with the termination «-ine» instead of «-ic acid», because they exhibit amide groups. For asparagine, R=CH_2CONH_2 and for glutamic acid, R=CH_2CH_2CONH_2.

It is not a coincidence that asparagine sounds a lot like asparagus. Indeed, it was first isolated from this vegetable’s juice, which is why it carries a similar name. In fact, the extraction of this molecule was done before that of aspartic acid in 1806.

Glutamine is the most abundant amino acid in the body because it is used to make other amino acids, nucleotides, antioxidants and more. It plays a special role in maintaining immunity since these cells use glutamine at a rate similar or above than that of glucose. For this reason, it is offered as a nutrition supplement after surgery, and for many athletes after they have overcome an illness.

But glutamine is not all that beneficial. Some cancers rely on glutamine so much that there are specific oncogenes in charge of regulating the cell’s consumption of glutamine. The enzyme glutamine synthetase can make glutamine from glucose, potentially sustaining cancer cells for longer.

Arginine, Histidine and Lysine

Last, but certainly not least are the basic amino acids. These contain at least one additional amine. Arginine has R=CH_2CH_2CH_2NHCNH_2NH_2^+, histidine has R= CH_2C_3H_3N_2 and lysine, the longest chain amino acid, has R=CH_2CH_2CH_2CH_2NH_3^+.

Arginine has been linked to treating cardiovascular disease due to how the body can convert it into nitric oxide, a vasodilator. Another interesting fact about arginine is that its name is derived from a Greek word (arginoeis) meaning brightly shining, like silver. However, it was purified from a yellow plant, lupin in 1886.

Histidine is used to make histamine in the body. This is the compound that causes allergic reactions when our non-specific immune system recognizes an agent as foreign. Furthermore, histidine is involved in the regulation of trace metals such as molybdenum, nickel and mercury, to eventually eliminate them from the body, since it can bind metals under basic conditions.

Lysine plays a role in epigenetic modifications. DNA wraps around histones to form a condensed version of genetic material called «string of pearls». The combination and tight packaging of this structural element is responsible for assembling chromosomes. To access the DNA from these histones though, it is necessary that they unwind. Nevertheless, some genes are silenced by environmental factors or are not needed in certain cells which is what causes them to suffer epigenetic modifications. Common ones include methylation, acetylation or ubiquitination. Because histones are proteins, they contain lysines and it has been shown that methylation occurs on those residues. This later impacts gene expression and transcriptional regulation.

Conclusion

I hope that no matter your level of prior knowledge, you have learnt something new about the building blocks of our molecular machines: proteins.

Bibliography

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