Nucleic Acids

Nucleic acids are long strings of nucleotides that end up forming the basis of our genetic material in addition to serving other functions. Simply put, nucleic acids are DNA and RNA.

Nitrogenous Bases

The most basic building block of our nucleic acids are the nitrogenous bases. These bases fall into two major categories, pyrimidine, and purines which describe the number of rings found in the base. Pyrimidines are hexagonal with one ring in their structure while purines contain two rings one of which is six-membered the other of which is five-membered. I remember that a pyrimidine only has one ring by imagining a hexagon folding up into a pyramid.

Within the purines are adenine and guanine while the pyrimidines contain thymine, cytosine, and uracil. Although a bit annoying we need to recognize, not memorize, the individual structures of each. Additionally, we should understand how to number each one, as well as the MCAT, likes to ask about the addition of molecules to specific areas of cyclic molecules.

A, T, C, G and U

I like to work through a flow chart when recognizing the bases that way I don’t have to try and remember quite as much information.

First, we start with the total number of rings in the base. If there are two we are dealing with a purine which is either adenine or guanine. I use the mnemonic PURe As Gold to remember this. PURines are Adenine and Guanine.

From there I check to see if there is oxygen on the ring. If no then the base is adenine, which I think of Add Ns because it only has nitrogen in its ring strucutre. Guanine on the other has an oxygen so I remember it as Gonine.

If on the other hand you only have one ring present then you are dealing with a pyrimidine. I don’t have a mnemonic for this since it is easy to remember PURe As Gold then assign the remaining bases, C, T, and U, as pyrimidines. From there we will use the names to help us remember what they look like. Thymine has a methyl, cytosine has one oxygen and uracil has two oxygens arranged in a U-shape.

Numbering

Additionally, we need to understand how to number the cyclic components of each nitrogenous base. Unfortunately, they don’t all start and end in the same place as is the case with carbohydrates. However, all the pyrimidines follow the same numbering scheme, as do the purines.

For the pyrimidines we will always start counting at the bottom-most nitrogen. Then we will number in a clockwise fashion around the remainder of the ring.

In contrast in the purines we will always start counting at the top left nitrogen in the six-membered ring. The numbering will then proceed in a counterclockwise direction all the way around the first ring then start at the top of the five-membered ring and continue around clockwise.

Chemical Properties

For the most part, all of the nitrogenous bases have the same properties. Of all of their various properties there two that are important on the MCAT. First, is the ability of nitrogenous bases to form hydrogen bonds with one another. The second is that they are all aromatic and as a result are able to form pi-stacking interactions.

Since hydrogen bonds are able to form between O-H, N-H, and F-H bonds and another H-bond acceptor there are numerous points at which each nitrogenous base can bond with one another. However, the only pairings that we end up seeing in normal non-damaged DNA are adenine bonding with thymine or uracil and guanine bonding with cytosine.

This occurs because each has a matching set of H-bond donors and acceptors. In AT or AU pairings, there will end up being two hydrogen bonds while in GC pairing there will be three. Although you might have been taught that the one additional H-bond is a substantially stronger intermolecular bond this is actually incorrect. Turns out that pi stacking interactions account for the major stability differences of GC pairings as compared to AT pairings.

Since the bases are all aromatic their pi electrons are delocalized. As a result, the partially negative portions of one base can stack with the partially positive element of another base. Although both AT/AU pairings and GC pairings possess pi-stacking interactions the GC pi stacking interactions are far more stable. So organisms like thermophiles (think bacteria living in hot springs) tend to have a high GC content in their DNA in order to keep their DNA together despite extreme temperatures.

Nucleosides

Nucleosides are nitrogenous bases with a side of sugar. Specifically, they will have a ribose or a deoxyribose connected at the 9th position on purines and the 1st position on pyrimidines. Here the identity of the sugar determines whether or not the molecule is going to be ribonucleic acid (RNA) or deoxyribonucleic acid (DNA). With RNA having all riboses and DNA having all deoxyriboses.

Nucleotides

Nucleotides are nucleosides with phosphate groups (PO₄^3-) attached to the C5′ off their sugar molecule. Not all nucleotides are the same though. Not only can the identity of their nitrogenous bases be different but the number of phosphates attached to their sugar molecule can be different too.

This is where we get molecules like dGTP or deoxyguanidine triphosphosphate. Let’s look at the name of this molecule more closely so we can easily intuit the different forms that nucleotides can take.

First up we have guani- which tells us that this is a guanidine the -ine tells us that this is a nucleoside specifically a deoxyribose since there is a deoxy prefix. Now for the tri- which tells us how many phosphates are attached to the sugar. All in all this molecule is guanidine with three phosphates attached. If this were in RNA then the deoxy- prefix would be gone.

Base Name	Nucleoside	Nucleotides by # of Phosphate (1,2,3)
Adenine	(Deoxy)Adenosine	(d)ATP, (d)ADP, (d)AMP
Guanine	(Deoxy)Guanosine	(d)GTP, (d)GDP, (d)GMP
Cytosine	(Deoxy)Cytidine	(d)CTP, (d)CDP, (d)CMP
Uracil	(Deoxy)Uridine	(d)UTP, (d)UDP, (d)UMP
Thymine	Deoxythymidine	dTTP, dTDP, dTMP

Nucleotides have a wide range of important functions within cells. For example, ATP and GTP are one of the major energy sources in our bodies at a cellular level. While dADP, dTDP, dCDP, and dGCP function as the building blocks of our DNA and molecules such cAMP or cyclic AMP function to help regulate signaling cascades downstream of G-protein coupled receptors.

Nucleic Acids

Finally nucleic acids are multiple nucleotides that come together in chains. We only have two types DNA and RNA, which we will look in detail in the upcoming sections.