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Nucleic acids

Building Bridges to Knowledge

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Hydrolysis of nucleic acids results in the formation of nucleotides, and hydrolysis of nucleotides results in the formation of nucleosides and phosphoric acid. Hydrolysis of nucleosides produces two purine bases, two pyrimidine bases and a pentose sugar. The identity of the purine and pyrimidine bases, and the pentose sugar depends on the structure of the nucleoside. There are two kinds of nucleic acids, and both are very large, and both have repeating nucleotide units. One type is referred to as DNA, deoxyribonucleic acid. DNA is found in cell nuclei. The other type is referred to as RNA, ribonucleic acid. RNA is found in all parts of the cell. Hydrolysis of DNA leads to two purine bases, adenine (1) and guanine (2) and two pyrimidine bases, cytosine (3) and thymine (4), phosphoric acid, and 2-deoxyribose (5), a pentose sugar. The following reaction schema represents the hydrolysis of DNA.

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Hydrolysis of RNA leads to two purine bases, adenine (1) and guanine (2) and two pyrimidine bases, cytosine (3) and uracil (6), phosphoric acid, and ribose (7), a pentose sugar. The following reaction schema represents the hydrolysis of RNA.

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Nucleosides are purine or pyrimidine bases with ribose or deoxyribose attached. When ribose is attached to a purine or pyrimidine base, it is referred to as a ribonucleoside. When 2-deoxyribose is attached to a purine or pyrimidine base, it is referred to as a deoxyribonucleoside. Adenosine (8); uridine (9); guanine (10); cytidine (11); and deoxythymidine (12) are examples of nucleosides.

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Ten (10) nucleosides are theoretically possible, but only eight are observed in nature. Though theoretically possible, thymine is not found in the natural environment with ribose. Though theoretically possible, uracil is not found in the natural environment with 2-deoxyribose. Nucleoside derivatives have been useful in medicine. For example, puromycin (13), a derivative of adenosine, obtained from Streptomyces Alboniger cultures, has been used as an antibiotic and an anticarcenogenic agent.

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Nucleotides are phosphate esters of nucleosides. For example, adenosine monophosphate (14) is the phosphate ester of adenosine. Adenosine monophosphate, also referred to as adenylic acid, is frequently abbreviated as AMP.

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Other examples of nucleotides are thymidine monophosphate, TMP, (15) and deoxythymidine monophosphate, DMP, (16). TMP does not exist in biological systems.

Nucleotides are the monomers of DNA and RNA. The diphosphate ester of adenosine is adenosine diphosphate, ADP, (17).

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ADP is involved in metabolic and biosynthetic processes. The triphosphate ester of adenosine is adenosine triphosphate, ATP, (18).

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Cyclic AMP (19) is a mediator in the synthesis of proteins and steroids. Cyclic AMP is also used in the metabolism of carbohydrates and fats.

Nucleic acids are polymers of nucleotides. Following is an illustration of the primary structure of nucleic acids. The HO groups attached to the phosphorous atoms contain hydrogen atoms that are ionizable making the molecule an acid.

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RNA contains the purine bases adenine and guanine, and the pyrimidine bases cytosine and uracil, and deoxyribose. Structure 21 is the primary structure of the RNA monomer. The primary structure of RNA is a polymer consisting of repeating units of the monomer represented by structure 21.

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DNA contains the purine bases adenine and guanine and the pyrimidine bases cytosine and thymine and ribose. Structure 22 is the primary structure of the DNA monomer. The primary structure of

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DNA is a polymer consisting of repeating units of the monomer represented by structure 22.

The primary structure of nucleic acids is more complex than the primary structures of proteins. It took Robert William Holley, of Cornell University, seven years to work out the primary structure for alanine transfer RNA. Alanine t-RNA contains seventy-seven (77) nucleotide units. Robert Holley received the 1968 Nobel Prize in Medicine for his work.

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The Secondary Structures of Nucleic Acids James Watson and Francis Crick worked out the secondary structures of nucleic acids in 1953. They used x-ray analysis to determine that the secondary structure was like a spiral staircase. They received the Nobel Prize for their work in 1962. Prior to the work of Watson and Crick, Erwin Chargaff showed that the molar amounts of adenosine equals the amount of thymine and the molar amounts of quinine equals the molar amounts of cytosine. These data helped Watson and Crick to determine the double helical structure for DNA.

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Adenine pairs with thymine and thymine pairs with adenine, guanine pairs with cytosine, and cytosine pairs with guanine by molecular association (hydrogen bonding). For example, molecular association of thymine with adenine may be illustrated in the following manner.

The molecular association of cytosine and guanine can be illustrated in the following manner.

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Note that a pyrimidine base is paired with a purine base, and the distance between the purine and pyrimidine bases in DNA is 1.085 nanometers. This distance is important in the helical arrangement, because if two purine bases paired, then they would occupy too much space for a double helical arrangement; and if two pyrimidine bases paired, then they would not occupy enough space for a double helical arrangement. The pairing of a purine base with a pyrimidine base with a distance of 1.085 nanometers is optimal for the spatial formation of the DNA double helix. Also, the purine and pyrimidine base pairing with an optimum distance of 1.085 nanometers allows for ten base pairs per turn of the double helix where the acidic phosphate units are on the out side of the helix. Proteins can wrap around the double helix where the proton goes from phosphate units of DNA to lysine and arginine side chains of the proteins to give a positive charge to hold the proteins to the DNA by salt bridges. RNA consists of a single strand of nucleic acids with some internal folding with some sections exhibiting double helical arrangements. DNA is the basic material that makes species uniquely different. DNA is found in the chromosomal nuclei of cells. There are variable

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chromosomes in different species, and human beings have 46 chromosomes. The chromosomes are in nuclei, and genes make up the chromosomes. Genes are made up of DNA in the double helix. When the helix separates, it can replicate itself. The arrangement of bases along the DNA chain stores information in the DNA that gives directions for building organisms. For example, the three bases cytosine-guanine-thymine sends a different message than the three bases guanine-cytosine-thymine.

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RNA reads the DNA message, and DNA directs the synthesis of proteins by its code. A portion of the DNA message is transcribed to the messenger RNA (m-RNA). The DNA double helix partially unzips and a limited portion of one DNA strand directs the synthesis of the single-stranded m-RNA molecule. Following is a representation of this process where A = adenine; T =thymine; G = guanine; C = cytosine Once the new strands are formed, the encoded m-RNA is read and translated into a protein structure. The m-RNA goes from the nucleus to the cell’s cytoplasm where it becomes attached to ribosomes where the genetic code is deciphered. Transfer RNA (t-RNA), in the cytoplasm, translates the purine and pyrimidine base sequencing from the m-RNA into amino acid sequences for a

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specific protein molecule. Transfer RNA has a looped structure where one end has three bases that carry a codon for a specific kind of amino acid. For example, the t-RNA with the bases cytosine-cytosine-cytosine is specific for glycine (the simplest amino acid) and guanine-cytosine-guanine is specific for arginine, an amino acid with basic properties. Proteins are specific sequences of amino acids that are prepared in vivo from the appropriate pairing of purine and pyrimidine bases of DNA nucleotides that are replicated by m-RNA and t-RNA with an anticodon to carry a specific amino acid to be attached to the developing protein. For example, m-RNA with cytosine-adenine-guanine attached could molecularly associate with a t-RNA with the anticodon sequence of bases guanine-uracil-cytosine bases providing the codon and anticodon specific for carrying glutamine to form a peptide bond in the in vivo synthesis of a protein. The m-RNA could also have codon cytosine-adenine-cytosine attached that would molecular associate with the anticodon guanine-uracil-guanine on the t-RNA specific for carrying histidine to form a peptide bond in the in vivo synthesis of a protein. The two amino acids, guanine and histidine would form a peptide bond, and sequencing with other m-RNA codons and t-RNA anticodons would continue with the formation of amide bonds until a specific protein has been synthesized. The simple peptide connection gly-leu could be synthesized by a m-RNA with codon sequence that would align with t-RNA with the anticodon sequence for delivery gly, and m-RNA codon sequence that would align with t-RNA with the anticodon for leucine (leu). Such a model could be illustrated in the following manner.

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Refer to the following Website for a tabulation of DNA base triplets and RNA codons and anticodons. http://waynesword.palomar.edu/codons.htm

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Problems Nucleic Acids 1. Draw formulas for:

(a) β-D-ribose 5-phosphate (b) α-D-ribose 3-phosphate (c) Adenosine 5’-triphosphate

2. Write formulas showing hydrogen bonding between:

(a) uracil and cytosine (b) uracil and adenine (c) uracil and guanine

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3. A portion of a DNA molecule has the following structure:

Suggest a structure for the partial complementary strand.

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4. What is(are) the tripeptide(s) that would be found by the sequence of m-RNA condons in (a) and (b)? (a) UUU-UAU-ACU (b) UUU-UAC-ACU

5. Give a rationale for the following observation:

The denaturation temperature of DNA increases with guanosine cytosine content

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Solutions to Problems

1. Draw formulas for: (a) β-D-ribose 5-phosphate

(b) α-D-ribose 3-phosphate

(c) Adenosine 5’-triphosphate

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2. Write formulas showing hydrogen bonding between:

(a) uracil and cytosine

(b) uracil and adenine

(c) uracil and guanine

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3. A portion of a DNA molecule has the following structure:

Suggest a structure for the partial complementary strand.

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4. What is(are) the tripeptide(s) that would be found by the sequence of condons in (a) and (b)?

(a) UUU-UAU-ACU phe-tyr-thr (b) UUU-UAC-ACU phe-tyr-thr 5.

Give a rationale for the following observation: The denaturation temperature of DNA increases with the addition of guanosine-cytosine moieties. As illustrated in the following structure, guanine-cyctosine exhibits three hydrogen bonding sites; whereas, the other base pairs have two hydrogen bonding sites. An increase in hydrogen bonding results in an increase in melting point or an increase in boiling point or an increase in denaturation temperature. Therefore, the denaturation temperature of DNA would increase with increasing guanine-cytosine content in the DNA molecule.