Nucleotide Structure

Nucleic acids (both RNA and DNA) are polymers made up of monomers called mononucleotide units (MNU in the diagram). These mononucleotide units are joined together by intermolecular dehydration reactions that form phosphate ester bonds. Those reactions are, of course, catalyzed by specialized enzymes.

MNU + MNU + MNU + MNU
special	Ż	enzymes
žMNUžMNUžMNUžMNUž

The nucleotide units themselves are made up of smaller types of components. Each nucleotide contains a phosphate unit, a sugar unit, and a heterocyclic base unit. (Also look at the diagram at the bottom of Example 4 in your workbook.)

MNU = PhosphatežSugaržBase

Phosphate

The phosphate unit can be represented either as a phosphate ion or as phosphoric acid molecule. As you look at various representations of this in different places, you will see both approaches used. Because of the acid strength of phosphoric acid and the base strength of phosphate ion, something part way in between, such as the dihydrogen phosphate ion, is probably closer to the truth as far as the form in which the phosphate actually exists in solution.

Structures of phosphate ion, dihydrogen phosphate ion and phosphoric acid. [69004.jpg]

Note that these representations show the top oxygen atom bonded to the phosphorous by what appears to be a double bond. Its not really a double bond, but it serves to satisfy our presumed requirement that oxygen has two bonds.

If you look at the electron dot representation of either the ion or the molecule, you will see that there are two electrons (one pair) not four electrons (two pairs) shared between the oxygen and the phosphorous. So, it is really not a double bond, but yet the oxygen does have all the eight electrons that it is supposed to have in its valence shell.

Lewis structures for phosphate ion and phosphoric acid. [69005.jpg]

Note also, that when you look at the phosphate ion in this way, there's really no difference between the three oxygen atoms that are presumed to "have a charge" and the one oxygen atom that "doesn't have a charge."

Another important thing to keep in mind as we look at the structure of nucleic acids is that two of the oxygens (or OHs) of the phosphate group (or phosphoric acid molecule) will be used to bond this unit to sugar molecules.

Sugar

The sugar that is part of a nucleotide is a 5-carbon atom sugar in its ring form. It will either be ribose in RNA or deoxyribose in DNA. The "deoxy" simply means that the ribose molecule has lost an oxygen. That missing oxygen happens to be from the second carbon, so the more correct name for deoxyribose is 2-deoxyribose. (These are also shown in Examples 4 and 5 in your workbook.)

Structures of ribose and 2-deoxyribose. [69006.jpg]

Because the last asymmetric carbon atom has an OH to the right, these molecules are sometimes given the more complete names of D-ribose and also D-2-deoxyribose. More commonly they are simply referred to as ribose and deoxyribose.

Structures of D-ribose and D-2-deoxyribose. [69007.jpg]

It is the ring form of the ribose and deoxyribose that are used in the nucleotide units. Each of the OHs in these molecules serves a particular function. Ribose is shown here, but these comments apply to deoxyribose as well.

	The double-bonded oxygen on the first carbon in the linear form becomes the beta OH that is used to bond to a base unit.
	The OH in the second position serves to distinguish between the ribose in RNA and the deoxyribose in DNA.
	The OH on the third carbon will bond to the phosphate group of other nucleotides.
	The OH group on the fourth carbon is involved in the closure of the ring.
	The OH group on the fifth carbon is what bonds to the phosphate unit of this particular nucleotide.

Structure of ribose with numbered carbon atoms. [ribnum2.gif]

Heterocyclic Bases

Several different bases are found in nucleotides. They are heterocyclic bases or sometimes referred to as nitrogenous bases because they contain nitrogen within the rings. The fact that they are bases is actually irrelevant for the function that they serve and we really won't be paying attention to their base properties. (Structures for these compounds are also shown at the top of Example 4 in your workbook.)

Pyrimidines

Some have one ring and are similar in structure to the compound pyrimidine and, because of that, they are called the pyrimidines or the pyrimidine bases. There are three of them and they are called cytosine which is found in both DNA and RNA, thymine, which is found only in DNA, and uracil, which is found only in RNA. The abbreviations C, T and U will be used extensively to refer to these compounds.


cytosine (C)	thymine (T)	uracil (U)

Purines

Some of these heterocyclic bases have two rings like the compound purine and, therefore, they are called the purines or the purine bases. They are adenine and guanine, represented by the letters A and G, and they are both found in DNA and RNA.


adenine (A)	guanine (G)

For future reference, it is important to note that within these compounds one NH will be involved in the bond to a sugar molecule (bottom right in these diagrams). The other NH's (and also Ns and double-bonded oxygens) will hydrogen bond to other bases. Similarly, in the pyrimidines, one NH (bottom in these diagrams) will be used to bond to the sugar molecule, either ribose or the deoxyribose. The other NHs and also double-bonded oxygens and nitrogen will be used to form hydrogen bonds to other bases.

Nucleosides

Now let's put the parts together. One of these heterocyclic bases bonded to a sugar molecule makes a nucleoside.

For example, when the heterocyclic base adenine bonds with the sugar molecule ribose by an intermolecular dehydration the nucleoside adenosine is formed. A water molecule is formed and a bond is formed between a nitrogen atom in the base and a carbon atom in the ribose. (This is also shown in Exercise 6 in your workbook.)

Equation showing the formation of adenosine from adenine and ribose. [69012.jpg]

Practice

To get some practice working with the combination of a heterocyclic base with a sugar molecule to make a nucleoside, write equations using structural formulas in which you will combine uracil with sugar and then also thymine with sugar to make their corresponding nucleosides. (These are also shown in Exercise 7 in your workbook.)

uracil + ribose Ž uridine

thymine + deoxyribose Ž deoxythymidine

Take some time now to draw the structural formulas that represent those reactions. Check with the instructor when you come to the lab to make sure that you have drawn these correctly.

Nucleotides

The next step is to combine the nucleoside with a phosphate to form a nucleotide.

In this case adenosine combines with the phosphate (or phosphoric acid) to form the nucleotide adenosine monophosphate. This is a dehydration reaction in water is released and a phosphate ester bond is formed. (This reaction equation is also shown in Example 8 in your workbook. The structure in that example shows the oxygen atom that is missing from the phosphoester bond in this diagram. See if you can find where the missing oxygen atom should be.)

Equation showing the formation of AMP from adenosine and phosphoric acid. [69015.jpg]

This nucleotide is often called adenosine monophosphate because it is made from adenosine with one phosphate group attached. It is quite often abbreviated as AMP. It can also be called adenylic acid.

Practice

To get practice working with the formation of nucleotides, write equations using structural formulas for the following reactions, which involve the formation of two additional nucleotides. (These are also shown in Exercise 9 in your workbook.) Try to avoid being distracted by the names, they are not our focus here. Instead, concentrate on the structures and the manner in which parts join together to make the nucleotides.

cytidine

phosphate
or
phosphoric acid

cytidine monophosphate (CMP)
or
cytidilic acid

guanine +

ribose +

phosphate
or
phosphoric acid

guanosine monophosphate (GMP)
or
guanilic acid

Check your answers with the instructor when you come into the lab.

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E-mail instructor: Sue Eggling

Clackamas Community College
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