CHAPTER OUTLINE
Nucleoside and Nucleotide Structure and Nomenclature
Nucleotide Derivatives in tRNAs
High-Yield Terms
Nucleoside: refers to the complex of nonphosphorylate ribose sugar and a nucleobase such as purine or pyrimidine
Nucleotide: refers to the complex of phosphorylated ribose sugar and a nucleobase such as purine or pyrimidine
Phosphodiester bond: the bond formed when the phosphate of 1 nucleotide is esterified to the hydroxyls of 2 ribose sugars typical in polynucleotides
Phosphoanhydride bond: an anhydride is a bond formed between 2 acids, a phosphoanhydride is the bond formed from 2 phosphoric acids such as with the β and γ phosphates of di- and triphosphate nucleosides, respectively
Chemically the nucleotides are basic compounds, which is the reason for the common term “bases” in the context of DNA and RNA. There are 5 major bases found in cells. The derivatives of purine are called adenine and guanine, and the derivatives of pyrimidine are called thymine, cytosine, and uracil. The common abbreviations used for these 5 bases are, A, G, T, C, and U, respectively.
As a class, the nucleotides may be considered one of the most important metabolites of the cell. Nucleotides are found primarily as the monomeric units comprising the major nucleic acids of the cell, RNA, and DNA. However, they also are required for numerous other important functions within the cell.
1. They serve as energy stores for future use in phosphate transfer reactions. ATP predominantly carries out these reactions.
2. They form a portion of several important coenzymes such as NAD+, NADP+, FAD, and coenzyme A.
3. They serve as mediators of numerous important cellular processes such as second messengers in signal transduction events. The predominant second messenger is cyclic-AMP (cAMP), a cyclic derivative of AMP formed from ATP.
4. They control numerous enzymatic reactions through allosteric effects on enzyme activity.
5. They serve as activated intermediates in numerous biosynthetic reactions. These activated intermediates include S-adenosylmethionine (S-AdoMet or SAM) involved in methyl transfer reactions as well as the many nucleotide-activated sugars involved in glycogen and glycoprotein synthesis.
Nucleoside and Nucleotide Structure and Nomenclature
The nucleotides found in cells are derivatives of the heterocyclic highly basic compounds, purine, and pyrimidine (Figure 4-1).
FIGURE 4-1: Purine and pyrimidine. The atoms are numbered according to the international system. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harper’s Illustrated Biochemistry, 29th Edition, Copyright 2012, New York: McGraw-Hill.
The purine and pyrimidine bases (Table 4-1) in cells are linked to carbohydrate and in this form are termed nucleosides. The nucleosides are coupled to D-ribose or 2′-deoxy-D-ribose through a β-N-glycosidic bond between the anomeric carbon of the ribose and the N9 of a purine or N1 of a pyrimidine. The carbon atoms of the ribose present in nucleotides are designated with a prime (′) mark to distinguish them from the backbone numbering in the bases. The base can exist in 2 distinct orientations about the N-glycosidic bond. These conformations are identified as syn and anti (Figure 4-2). The anti-conformation predominates in naturally occurring nucleotides.
FIGURE 4-2: The syn and anti conformers of adenosine differ with respect to orientation about the N-glycosidic bond. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harper’s Illustrated Biochemistry, 29th ed. New York, NY: McGraw-Hill; 2012.
Nucleosides are found in the cell primarily in their phosphorylated form and are called nucleotides. Nucleotides can exist in the mono-, di-, or tri-phosphorylated forms (Figure 4-3). Nucleotides are given distinct abbreviations to allow easy identification of their structure and state of phosphorylation. The monophosphorylated form of adenosine (adenosine-5-monophosphate) is written as AMP. The di- and tri-phosphorylated forms are written as, ADP and ATP, respectively.
FIGURE 4-3: ATP, its diphosphate, and its monophosphate. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harper’s Illustrated Biochemistry, 29th ed. New York, NY: McGraw-Hill; 2012.
The phosphate in a monophosphate nucleotide is linked via an ester bond to the ribose. The di- and tri-phosphates of nucleotides are linked by anhydride bonds. Acid anhydride bonds have a high ΔG0′ for hydrolysis imparting upon them a high potential to transfer the phosphates to other molecules. This property of the nucleotides results in their involvement in group transfer reactions in the cell.
The nucleotides found in the DNA are unique from those of the RNA in which the ribose exists in the 2′-deoxy form and the abbreviations of the deoxynucleotides contain a “d” designation. The monophosphorylated form of adenosine found in DNA (deoxyadenosine-5′-monophosphate) is written as dAMP (Figure 4-4).
FIGURE 4-4: Structures of AMP, dAMP, UMP, and TMP. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harper’s Illustrated Biochemistry, 29th ed. New York, NY: McGraw-Hill; 2012.
The nucleotide uridine is never found in the DNA while thymine is almost exclusively found in the DNA. Thymine is found in tRNAs but not in rRNAs or mRNAs. There are several less common bases found in the DNA and RNA. The primary modified base in DNA is 5-methylcytosine (see Chapter 35). A variety of modified bases appears in the tRNAs. Many modified nucleotides are encountered outside of the context of DNA and RNA that serve important biological functions.
Nucleotide Derivatives
The most common adenosine derivative is the cyclic form, 3-5-cyclic adenosine monophosphate, cAMP. Formation of cAMP is catalyzed by adenylate cyclase. The activation of adenylate cyclase occurs in response to the ligand binding to membrane receptors of the type termed G-protein–coupled receptors, GPCR (see Chapter 40). Cyclic-AMP is a very powerful second messenger involved in passing signal transduction events from the cell surface to internal proteins primarily through the activation of cAMP-dependent protein kinase, PKA. Cyclic-AMP is also involved in the regulation of ion channels by direct interaction with the channel proteins such as in the activation of odorant receptors by odorant molecules.
A cyclic form of guanosine 5-monophosphate (cGMP) is also produced in cells and acts as a second messenger molecule (Figure 4-5). In many cases its role is to antagonize the effects of cAMP. Formation of cGMP occurs in response to receptor-mediated signals similar to those for activation of adenylate cyclase. However, in this case it is guanylate cyclase that is coupled to the receptor. One of most significant cGMP-coupled signal transduction cascades is the activation of photoreception (see Chapter 8). Another is its role in vascular tone via effects within arterial smooth muscle cells (see Chapter 31).
FIGURE 4-5: cAMP, 3′,5′-cyclic AMP, and cGMP, 3′, 5′-cyclic GMP. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harper’s Illustrated Biochemistry, 29th ed. New York, NY: McGraw-Hill; 2012.
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