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Chapter 17 – Nucleic Acids and Protein Synthesis Nucleic Acids Nucleic acids are the components that make up the genetic material DNA (deoxyribonucleic acid). DNA is a macromolecule which contains all the genetic information – that is the genes – required to make any given organism. A second nucleic acid, RNA (ribonucleic acid) serves as an intermediary in converting DNA information into actual proteins. Nucleotides Nucleic acids are long chains, or unbranched polymers, made up of repeating units called nucleotides. A total of five different nucleotides are sufficient to create and store all the information in DNA to make every protein and all other components that make up any cell. Three separate chemical components linked together constitute a nucleotide molecule:

• A phosphate group • A pentose monosaccharide • A nitrogen-containing base.

In RNA, the five-membered monosaccharide ring is the aldopentose D-ribose. Hence the name ribonucleic acid (abbreviated RNA). In DNA, the monosaccaride has one small difference from ribose: absence of a hydroxyl group on carbon 2. This aldopentose missing a hydroyl group is known as D-2-deoxyribose. Nucleic acid containing deoxyribose is known as deoxyribonucleic acid (abbreviated DNA).

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The variability that produces five different deoxyribonucleic acids is in the type of nitrogen-containing base: three of the bases, cytosine (C), uracil (U), and thymine (T), differ only by differences in functional group substitutions to the parent compound, pyrimidine.

The remaining two nucleotide bases, adenine (A) and guanine (G), are derived from the parent compound purine. Differences in functional group substitutions differentiate A from G.

DNA contains the bases A, G, C, and T. RNA contains the bases A, G, C, and U.

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Synthesizing a Nucleotide 1. The formation of a nucleotide includes the attachment of the nitrogen-containing base to the C-1 carbon of D-ribose to form a nucleoside, with the release of H2O. For example, combining cytosine with D-ribose form the ribonucleoside cytidine

2. Add a phospate to the nucleoside. Nucleotides are finally formed by the addition of a phosphate group to the 5-hydroxyl group of the nucleoside.

The resulting nucleotide in this example is a ribonucleotide, cytidine 5ʹ′-monophosphate, a component of RNA abbreviated CMP. Note that with RNA, uracil (U) replaces thymine (T).

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Another example: Combine a deoxyribose and the purine adenine, and when phosphate is added, you have a component of DNA, deoxyadenosine 5ʹ′-monophosphate, abbreviated dAMP.

Naming a nucleoside: Ending

• If derived from a pyrimidine, add the ending – idine to the name. • If derived from a purine, add the ending – sine to the name.

Prefix

• If derived from a deoxyribose, add the prefix Deoxy – to the name.

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Nucleic Acid Polymers (DNA and RNA) The phosphate ester on a nucleotide can react with a hydroxyl group on another nucleotide to form a phosphate diester.

This process of linking alternating phosphate and sugar groups can continue to form a polynucleotide and eventually a long chain polymer. The polymer will have one free phosphate at the 5ʹ′ end, and one free hydroxyl at the 3ʹ′ end. The identity and sequence of the nucleotides linked together – specifically the bases – distinguish one polynucleotide from another.

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The previous sequence can be abbreviated to focus on the part where the information is stored, the purine and pyrimidine bases.

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Reading from the 5ʹ′ end, this polynucleotide would be named CATG. DNA – The Double Helix Molecule DNA consists of two very long polynucleotide strands that wind into a right-handed double helix. The two strands run in opposite directions; one runs from the 5’ end to the 3’ end and the other runs from the 3’ end to the 5’ end. The sugar-phosphate groups lie on the outside of the helix and the bases lie on the inside

A purine base on one strand always hydrogen bonds with a pyrimidine base on the other strand. Thus, there are complementary base pairs that always hydrogen bond together in a particular manner. For example (see below):

• Adenine pairs with thymine with 2 hydrogen bonds to form an A—T base pair.

• Cytosine pairs with guanine using 3 hydrogen bonds to form a C—G base pair.

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The information stored in DNA is used to direct the synthesis of proteins in the following sequence:

• Replication is the process by which DNA makes a copy of itself when a cell divides.

• Transcription is the ordered synthesis of RNA from DNA; the genetic

information stored in DNA is passed onto RNA.

• Translation is the synthesis of proteins from RNA; the genetic information determined the specific amino acid sequence of the protein.

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Replication The original DNA molecule acts as a template to form two new DNA molecules, each of which contains a strand from the parent DNA and one new strand. The process begins with unwinding the two intertwined DNA strands (the double helix) by breaking the hydrogen bonds holding the molecules together. When the individual strands are exposed, an enzyme, DNA polymerase, catalyzes the replication (reproduction) of the two strands by forming a daughter strand of each parent strand. Each parent strand combines with a new daughter strand to form two new DNA molecules The identity of the bases on the template strand determines the order of the bases on the new strand. A must pair with T, and G must pair with C

Transcription Transcription is the process of translating the information in DNA into a carrier of this information, namely messenger Ribonucleic Acid or mRNA. RNA Like DNA, RNA is composed of nucleotides, but there are important differences. Physical differences: RNA molecules are much smaller than DNA molecules, and they exist as a single strand of nucleotides, not a double strand.

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Chemical differences: • The sugar is ribose rather than deoxyribose • A new base, uracil (U) is employed in place of thymidine (T).

Functional differences: There are three types of RNA molecules:

• Ribosomal RNA (rRNA) • Messenger RNA (mRNA) • Transfer RNA (tRNA)

The messenger RNA carries the specific information from the DNA molecule required for the synthesis of proteins. For example: DNA Template strand: 3’—C T A G G A T A C—5’ mRNA: 5’—G A U C C U A U G—3’ Note the substitution of U in the mRNA for T in the DNA The ribosomal RNA, along with some proteins, serves as a workbench for assembling the amino acids into protein The transfer RNA carries the specific amino acid specified by the DNA to the site of protein synthesis. The specificity of the tRNA for the mRNA resides in a three nucleotide sequence on the tRNA molecule known as an anticodon. An anticodon is a three nucleotide sequence which is complementary to a three nucleotide sequence on the mRNA.

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The Genetic Code A sequence of three nucleotides (a triplet) codes for a specific amino acid. Each triplet is called a codon. For example:

• UCA is a codon for the amino acid serine • UGC is a codon for the amino acid cysteine

With four different nucleotides in mRNA, there are 64 different ways to combine them into groups of three. Thus, many amino acids have more than one codon. For example, the amino acid serine has six different codons.

• UCU • UCC • UCA • UCG • AGU • AGC

The complete genetic code – the RNA triplets (codons) in mRNA – is given in Table 17.3 in your textbook. Translation and Protein Synthesis

Relating codons, anticodons, and amino acids

mRNA Codon tRNA Anticodon Amino Acid

ACA UGU threonine

GCG CGC alanine

AGA UCU arginine

UCC AGG serine

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A summary of the process of transcription of the DNA information into mRNA, and translation of the mRNA into the specified proteins is outlined below.

Mutations and Genetic Disease A mutation is a change in the nucleotide sequence in a molecule of DNA. A point mutation – the substitution of one nucleotide in the DNA for another – may or may not change the amino acid originally specified since for many amino acids, there are multiple codons. If the amino acid does not change, then this is known as a silent mutation.

On the other hand, in a protein such as hemoglobin, the substitution of an A in CCT to give CAT results in the substitution of the amino acid valine for the amino acid glutamate. This dramatically alters the function of the protein – its ability to carry oxygen – causing the fatal genetic disease sickle cell anemia.

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A deletion mutation, the complete loss of a nucleotide, can occur.

An insertion mutation can occur where an additional nucleotide is inserted into the DNA

Deletion or insertion mutations are much more problematic.