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Nucleic Acids*#

Nucleic acids

Nucleic acids are molecules made up of nucleotides that carry the genetic blueprint of a cell. Each nucleotide is made up of a pentose sugar, a nitrogenous base, and a phosphate group. There are two types of nucleic acids: DNA and RNA. DNA carries the genetic blueprint of the cell and is passed on from parents to offspring. Double-stranded DNA has a helical structure with the two strands running in opposite directions. The two strands are connected by hydrogen bonds, and chemically complementary to each other. Interactions known as "base stacking" interactions also help stabilize the double helix. RNA can either be single stranded, or double stranded and is made of a pentose sugar (ribose), a nitrogenous base, and a phosphate group. RNA is involved in protein synthesis as a messenger and as a regulator of protein synthesis, other regulatory processes, and some catalytic activities. Messenger RNA (mRNA) is copied from the DNA, is exported from the nucleus to the cytoplasm, and contains information for the construction of proteins. Ribosomal RNA (rRNA) is a part of the ribosomes at the site of protein synthesis, whereas transfer RNA (tRNA) carries the amino acid to the site of protein synthesis. microRNA regulates the use of mRNA for protein synthesis.

Nucleotide structure

The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). The main common difference between these two types of nucleic acids is the presence or absence of a hydroxyl group at the C2 position, also called the 2' position, of the ribose. DNA lacks the ribose and contains a hydrogen atom at that position, hence the name, "deoxy" ribonucleic acid whereas RNA has a hydroxyl functional group at that position.  

DNA and RNA are made up of monomers known as nucleotides. Individual nucleotides condense with one another to form a nucleic acid polymer. Each nucleotide is made up of three components: a nitrogenous base (for which there are five different types), a pentose (five-carbon) sugar, and a phosphate group. These are depicted below.

Figure 1. A nucleotide is made up of three components: a nitrogenous base, a pentose sugar, and one or more phosphate groups. Carbon residues in the pentose are numbered 1′ through 5′ (the prime distinguishes these residues from those in the base, which are numbered without using a prime notation). The base is attached to the 1′ position of the ribose, and the phosphate is attached to the 5′ position. When a polynucleotide is formed, the 5′ phosphate of the incoming nucleotide attaches to the 3′ hydroxyl group at the end of the growing chain. Two types of pentose are found in nucleotides, deoxyribose (found in DNA) and ribose (found in RNA). Deoxyribose is similar in structure to ribose, but it has an -H instead of an -OH at the 2′ position. Bases can be divided into two categories: purines and pyrimidines. Purines have a double ring structure, and pyrimidines have a single ring.
Attribution: Marc T. Facciotti (original work)

The nitrogenous base

The nitrogenous bases of nucleotides are organic molecules and are so named because they contain carbon and nitrogen. They are bases because they contain an amino group that has the potential of binding an extra hydrogen, and thus acting as a base by decreasing the hydrogen ion concentration in the local environment. Each nucleotide in DNA contains one of four possible nitrogenous bases: adenine (A), guanine (G) cytosine (C), and thymine (T). RNA contains adenine (A), guanine (G) cytosine (C), and uracil (U) instead of thymine (T). 

Adenine and guanine are classified as purines. The primary distinguishing feature of the structure of a purine is double carbon-nitrogen ring. Cytosine, thymine, and uracil are classified as pyrimidines. These are distinguished structurally by a single carbon-nitrogen ring. You will be expected to recognize that each of these ring structures is decorated by functional groups that may be involved in a variety of chemistries and interactions.

Note: practice

Take a moment to review the nitrogenous base in Figure 1. Identify functional groups as described in class. For each functional group identified, describe what type of chemistry you expect it to be involved in. If hydrogen bonded, does the functional group act as a donor or acceptor?

The pentose sugar

The pentose sugar contains five carbon atoms. Each carbon atom of the sugar molecule are numbered as 1′, 2′, 3′, 4′, and 5′ (1′ is read as “one prime”). The two main functional groups that are attached to the sugar are often referred in reference to the carbon number they are bound to. For example, the phosphate residue is attached to the 5′ carbon of the sugar and the hydroxyl group is attached to the 3′ carbon of the sugar. We will often use the carbon number to refer to functional groups on nucleotides so be very familiar with the structure of the pentose sugar. 

The pentose sugar in DNA is called deoxyribose, and in RNA, the sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the 2' carbon of the ribose and its absence on the 2' carbon of the deoxyribose. Hence you can determine if you are looking at a DNA or RNA nucleotide by the presence or absence of the hydroxyl group on the 2' carbon atom—you will likely be asked to do so on numerous occasions (including exams).

The phosphate group

There can be anywhere between one and three phosphate groups bound to the 5' carbon of the sugar. When one phosphate is bound, the nucleotide is referred to as a Nucleotide MonoPhosphate (NMP). If two phosphates are bound the nucleotide is referred to as Nucleotide DiPhosphate (NDP). When three phosphates are bound to the nucleotide it is referred to as a Nucleotide TriPhosphate (NTP). The phosphoanhydride bonds between that link the phosphate groups to each other have specific chemical properties that make them good for various biological functions. The hydrolysis of the bonds between the phosphate groups is thermodynamically exergonic in biological conditions and nature has evolved numerous mechanisms to couple this negative change in free energy to help drive many reactions in the cell. Figure 2 shows an example of the hydrolysis of the nucleotide triphosphate ATP.

Note: "high-energy" bonds

The term "high-energy bond" is used A LOT in biology. It is, however, one of those shortcuts we referred to earlier. The term refers to the amount of negative free energy associated with the HYDROLYSIS of that bond! The water is important. While we have tried to minimize the use of the vernacular "high energy" when referring to bonds, keep the above in mind when you are reading or listening to discussions in biology.


Figure 2. ATP (adenosine triphosphate) has three phosphate groups that can be removed by hydrolysis to form ADP (adenosine diphosphate) or AMP (adenosine monophosphate).The negative charges on the phosphate group naturally repel each other, requiring energy to bond them together and releasing energy when these bonds are broken.
Attribution: Marc T. Facciotti (original work)

Double helix structure of DNA

DNA has a double helix structure (shown below). The sugar and phosphate lie on the outside of the helix, forming the backbone of the DNA. The nitrogenous bases are stacked in the interior, like the steps of a staircase in pairs; the pairs are bound to each other by hydrogen bonds. Every base pair in the double helix is separated from the next base pair by 0.34 nm. The two strands of the helix run in opposite directions, meaning that the 5′ carbon end of one strand will face the 3′ carbon end of its matching strand. This is referred to as antiparallel orientation.

Figure 3. Native DNA is an antiparallel double helix. The phosphate backbone (indicated by the curvy lines) is on the outside, and the bases are on the inside. Each base from one strand interacts via hydrogen bonding with a base from the opposing strand.
Attribution: Marc T. Facciotti (original work)

In a double helix, certain combinations of base pairing are chemically more favored than others based on the types and locations of functional groups on the nitrogenous bases of each nucleotide.  In biology we find that adenine (A) is chemically complementary with thymidine (T) and guanine (G) is chemically complementary with cytosine (C), as shown below. We often refer to this pattern as "base complementarity" and say that the antiparallel strands are complementary to each other. For example, if the sequence of one strand is of DNA is 5'-AATTGGCC-3', the complementary strand would have the sequence 5'-GGCCAATT-3'. 

Figure 4. In a double-stranded DNA molecule, the two strands run antiparallel to one another so that one strand runs 5′ to 3′ and the other 3′ to 5′. The phosphate backbone is located on the outside, and the bases are in the middle. Adenine forms hydrogen bonds (or base pairs) with thymine, and guanine base pairs with cytosine. 
Created by Ivy Jose

Functions and roles of nucleic acids and nucleotides

Nucleic acids play a variety of roles in in cellular process besides being the information storage molecule. Nucleic acids, RNA in particular, are believed to be the first biologically active molecules during a period referred to as the "RNA world" when catalytic RNA were thought to serve the dual role as catalysts and information storing molecules. Remnants of the RNA world can be seen in many riboprotein complexes essential for life. In these RNA-Protein complexes, the RNA serves both catalytic and structural roles. Examples of such complexes include, ribosomes, RNases, splicesosome complexes, and telomerase. Nucleotides such as ATP and GTP also serve as mobile short-term energy transport units for the cell. Nucleotides also play important roles as co-factors (in addition to energy vehicles) for many enzymatic reactions. Like lipids, proteins, and carbohydrates, nucleic acids and nucleotides play a wide variety of roles in the cell.