Biochem 8.1 Nucleotides PDF

# Lesson 8.1 Nucleotides ## Chapter 8: Nucleotides and Nucleic Acids ### Introduction Nucleotides are a class of molecules that store and transmit genetic information, provide energy for thermodynamically unfavorable reactions, and facilitate various biologically important oxidation-reduction reacti...

# Lesson 8.1 Nucleotides ## Chapter 8: Nucleotides and Nucleic Acids ### Introduction Nucleotides are a class of molecules that store and transmit genetic information, provide energy for thermodynamically unfavorable reactions, and facilitate various biologically important oxidation-reduction reactions. These molecules consist of a nitrogenous base (ie, a system of one or more nitrogen-containing aromatic rings) glycosidically linked to a sugar (usually ribose or deoxyribose). The sugar contains at least one phosphate group, typically linked to the sugar's highest-numbered carbon atom. Figure 8.1 shows the general structure of a nucleotide. - **Phosphate group** - **Nitrogenous base** - **Sugar** - **= H in DNA (deoxyribose sugar) and OH in RNA (ribose sugar)** - Figure 8.1: General structure of a nucleotide This lesson explains: - the structures of the nitrogenous bases used in DNA and RNA - the arrangement of the components in a nucleotide - nucleotides other than those in DNA and RNA - the biological roles that nucleotides perform ### 8.1.01 Nitrogenous Bases Just as amino acids are identified by their side chains, nucleotides are identified by their nitrogenous bases. The most abundant bases are those found in nucleic acids (ie, DNA, RNA). The structures of these bases are commonly tested on the exam. - **Purines** are adenine and guanine - **Pyrimidines** are cytosine, Thymine, and uracil The pyrimidine bases consist of a single six-membered aromatic ring that contains two nitrogen atoms. Figure 8.2 shows the structure of pyrimidine. - **Figure 8.2:** The structure of pyrimidine, from which pyrimidine bases are derived. The purine bases consist of two fused aromatic rings, one with five members and one with six members. Figure 8.3 shows the structure of purine. - **Figure 8.3:** Structure of purine with similarities and differences to pyrimidine. ### 8.1.02 Chemical Modifications of Nitrogenous Bases The nitrogenous bases in the nucleotides of DNA and RNA are susceptible to certain chemical modifications. These modifications can cause incorrect base pairing, which can lead to mutations. This concept provides information about several of the most common nucleotide modifications and their biological relevance. #### Tautomerization Tautomerization is the transfer of a proton from one site within a molecule to another site in the same molecule. This process also involves movement of a double bond. Each of the nitrogenous bases found in DNA and RNA can undergo tautomerization. - Adenine and cytosine both contain amino groups that can transfer a proton to the ring nitrogen while shifting a double bond to generate an imino group - Guanine, thymine, and uracil contain carbonyl groups linked to nitrogen, which is in turn linked to hydrogen. This functional group as a whole is a cross between a lactone and an amide (ie, a lactam). Transfer of the hydrogen atom to the carbonyl oxygen produces a hydroxyl group and results in a double bond shift. The result is that the nitrogen now carries a double bond (becoming more imine-like) and is a lactim. - Figure 8.9: Tautomerization of the nitrogenous bases. #### Deamination Adenine, guanine, and cytosine each contain one primary amino group (ie, a nitrogen atom bonded to two hydrogen atoms and one carbon atom). These amino groups can be removed and replaced by carbonyls in a process called deamination. - Figure 8.10: Deamination of several nitrogenous bases. #### Methylation Cytosine can become methylated at position 5. Unlike the other chemical modifications, cytosine methylation is commonly used for regulation of DNA expression. Therefore, many organisms have enzymes that intentionally cause cytosine methylation. Cytosine is shown before and after methylation in Figure 8.11. - Figure 8.11: Cytosine can be methylated at position 5. - Figure 8.12: Deamination of methylated cytosine produces thymine. ### 8.1.03 Nucleosides and Nucleotides When a carbohydrate (or deoxy carbohydrate derivative) forms a bond with a nitrogenous base, the result is a molecule that belongs to a class of compounds called nucleosides. In biological systems, the carbohydrate is typically ribose or deoxyribose. Just as amino acids have a constant backbone structure, the ribose or deoxyribose sugar is the constant backbone of a nucleoside. Figure 8.13 shows the furanose forms of ribose and deoxyribose. - Figure 8.13: Structures of ribose and deoxyribose in their furanose forms, which they adopt in nucleosides and nucleotides. Nucleosides are given names derived from the nitrogenous base involved in the glycosidic bond. - When adenine or guanine are attached to ribose, the molecule formed is called adenosine or guanosine, respectively. - Similarly, cytosine, thymine, and uracil become cytidine, thymidine, and uridine. - When the carbohydrate is deoxyribose, the names become deoxyadenosine, deoxyguanosine, and so forth. - Figure 8.14: General structures of pyrimidine and purine nucleosides. - Figure 8.15: Nucleosides found in DNA and RNA. The 5' carbon of a nucleotide is attached to a single phosphate group or to a chain of phosphate groups that are themselves linked to each other through phosphoanhydride bonds. - A nucleotide with a single phosphate group is a nucleoside monophosphate (NMP) - A nucleotide with two phosphates is a nucleoside diphosphate (NDP) - A nucleotide with three phosphates is a nucleoside triphosphate (NTP) - Figure 8.16: General structures of NMP, NDP, and NTP molecules. ### 8.1.04 Overview of Nucleotide Function Nucleotides are believed to be among the first molecules involved in giving rise to life. As such, these molecules perform many critical biological functions. This concept describes several aspects of nucleotide function, including genetic and nongenetic roles. #### Nucleotides in Genetics - DNA contains all the information necessary to produce the enzymes and proteins that carry out metabolism and other necessary functions. - Portions of DNA that encode proteins are read to produce mRNA, which ribosomes then translate into proteins. - The path from DNA to RNA to protein is called the central dogma of molecular biology and is depicted in Figure 8.19. - Figure 8.19: The central dogma of molecular biology. #### Metabolic Nucleotide Functions Nucleotides also play biological roles outside storage and transmission of genetic information. - Adenosine triphosphate (ATP) is a nucleotide that serves as the primary energy currency for all known life. - Various metabolic pathways involve nucleotides. - Figure 8.20: Examples of nucleotide involvement in several metabolic pathways. #### Regulatory Nucleotide Functions As discussed in Unit 2, many enzymes are tightly regulated to ensure that they are active only when the cell needs them. Nucleotides are highly involved in enzyme regulation. - Figure 8.21: Reduction and oxidation of NAD (or NADP) and FAD (or FMN). - Figure 8.22: G protein-coupled receptor pathways require the nucleotide GTP and often include conversion of ATP into cAMP. - Figure 8.23: Protein phosphorylation typically requires the nucleotide ATP, which becomes ADP after donating a phosphate group. The examples given in this concept are not comprehensive. However, they demonstrate how nucleotides play critical roles in almost every biological pathway.