NUCLEIC ACIDS

Dr. Hazim allawi Mohammed MBChB, MSc, Ph.D (Clinical Biochemistry)Assist Prof, Dept. of BiochemistryMosul Medical College

INTRODUCTION

Nucleic acids are biological elements required for both the storage and expression of genetic information in the living organisms.

There are two chemically distinct types of nucleic acids:

*Deoxyribonucleic acid (DNA) *Ribonucleic acid (RNA).

DNA, the store of genetic information, is present not only in chromosomes in the nucleus of eukaryotic organisms, but also in mitochondria and the chloroplasts of plants. Prokaryotic cells, which lack nuclei, have a single chromosome, but may also contain non-chromosomal DNA in the form of plasmids.

Although the genetic master plan of an

organism is contained in the sequence of deoxyribonucleotides in its (DNA), however, it is through the ribonucleic acid (RNA)—the “working copies” of the DNA—that the master plan is expressed.

The copying process, during which a DNA strand serves as a template for the synthesis of RNA, is called as “DNA transcription”.

Transcription produces messenger RNAs that are translated into sequences of amino acids (polypeptide chains or proteins), and ribosomal RNAs, transfer RNAs, and additional small RNA molecules (snRNA) that perform specialized structural, catalytic, and regulatory functions and are not translated

STRUCTURE OF DNA

DNA is a polymer of deoxyribonucleoside monophosphates (or deoxyribonucleotides) covalently linked by 3′→5′–phosphodiester bonds. With the exception of a few viruses that contain single-stranded (ss) DNA, DNA exists as a double-stranded (ds) molecule, in which the two strands wind around each other, forming a double helix.

In eukaryotic cells, DNA is found associated with various types of proteins (known collectively as nucleoprotein) present in the nucleus, whereas in prokaryotes, the protein–DNA complex is present in a non membrane-bound region known as the nucleoid.

3′→5′-Phosphodiester bonds

Phosphodiester bonds join the 3′-hydroxyl group of the deoxypentose of one nucleotide to the 5′-hydroxyl group of the deoxypentose of an adjacent nucleotide through a phosphate group.The resulting long, unbranched chain has polarity, with both a 5′-end (the end with the free phosphate) and a 3′-end (the end with the free hydroxyl) that are not attached to other nucleotides. The bases located along the resulting deoxyribose–phosphate backbone are always written in sequence from the 5′-end of the chain to the 3′-end.

Double helix

In the double helix, the two chains are coiled around a common axis called the axis of symmetry. The chains are paired in an antiparallel manner, that is, the 5′-end of one strand is paired with the 3′-end of the other strand.

In the DNA helix, the hydrophilic deoxyribose–phosphate backbone of each chain is on the outside of the molecule, whereas the hydrophobic bases are stacked inside. The overall structure resembles a twisted ladder. The spatial relationship between the two strands in the helix creates a major (wide) groove and a minor (narrow) groove.

These grooves provide access for the binding of regulatory proteins to their specific recognition sequences along the DNA chain. Certain anticancer drugs, such as dactinomycin (actinomycin D), exert their cytotoxic effect by intercalating into the narrow groove of the DNA double helix, thus interfering with DNA and RNA synthesis.

Base pairing

The bases of one strand of DNA are paired with the bases of the second strand, so that an adenine is always paired with a thymine and a cytosine is always paired with a guanine. The base pairs are perpendicular to the axis of the helix, therefore, one polynucleotide chain of the DNA double helix is always the complement of the other. Once the sequence of bases on one chain are known, the sequence of bases on the complementary chain can be determined.

The base pairs are held together by hydrogen bonds: two between A and T and three between G and C. These hydrogen bonds, plus the hydrophobic interactions between the stacked bases, stabilize the structure of the double helix.

Chargaff RuleChargaff Rule: In any sample of dsDNA, the amount of adenine

equals the amount of thymine, the amount of guanine equals the amount of cytosine, and the total amount of purines equals the total amount of pyrimidines. The base pairs are held together by hydrogen bonds: two between A and T and three between G and C.

Nucleotide Metabolism

•Ribonucleoside and deoxyribonucleoside phosphates (nucleotides) are essential for all cells. Without them, neither DNA nor RNA can be produced and, therefore, proteins cannot be synthesized or cells proliferate.

•Nucleotides also serve as carriers of activated intermediates in the synthesis of some carbohydrates, lipids, and proteins.

•They are structural components of several essential coenzymes, for example, coenzyme A, FAD, NAD+, and NADP+

Nucleotides, such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), serve as second messengers in signal transduction pathways.

In addition, nucleotides play an important role as

“energy currency” in the cell. Finally, nucleotides are important regulatory

compounds for many of the pathways of intermediary metabolism, inhibiting or activating key enzymes.

Nucleotide Structure

Nucleotides are composed of: a nitrogenous base, a pentose monosaccharide, one, two, or three phosphate groups.

The nitrogen-containing bases belong to two families of compounds: the purines and the pyrimidines.

The purine and pyrimidine bases found in nucleotides can be synthesized de novo, or can be obtained through salvage pathways that allow the reuse of the preformed bases resulting from normal cell turnover or from the diet.

Nucleosides

The addition of a pentose sugar to a base produces a nucleoside. If the sugar is ribose, a ribonucleoside is produced; if the sugar is 2-deoxyribose, a deoxyribonucleoside is produced.

Purine and pyrimidine structures

Purine nitrogenous bases are two: Adenine (A) and Guanine (G), while pyrimidine bases are three; Thymine (T), Cytosine (C), and Uracil (U). Both DNA and RNA contain the same purine bases: adenine (A) and guanine (G). Both DNA and RNA contain the pyrimidine cytosine (C), but they differ in their second pyrimidine base: DNA contains thymine (T), whereas RNA contains uracil (U). T and U differ in that only T has a methyl group

Unusual bases are occasionally found in some species of DNA and RNA, for example, in some viral DNA, and in transfer RNA. Base modifications include methylation, glycosylation, acetylation, or reduction. The presence of an unusual base in a nucleotide sequence may aid in its recognition by specific enzymes, or protect it from being degraded by nucleases.

The ribonucleosides of A, G, C, and U are named adenosine, guanosine, cytidine, and uridine, respectively.

The deoxyribonucleosides of A, G, C, and T have the added prefix, “deoxy-,” for example, deoxyadenosine.

*The compound deoxythymidine is often simply called thymidine, with out the “deoxy-” prefix being understood. why?

The carbon and nitrogen atoms in the rings of the base and the sugar are numbered separately with those of the pentose sugar are numbered 1′ to 5′. Thus, when the 5′-carbon of a nucleoside (or nucleotide) is referred to, a carbon atom in the pentose, rather than an atom in the base, is being specified.

Nucleotides as have been mentioned already are produced by the addition of one or more phosphate groups to a nucleoside. The first phosphate group is attached by an ester linkage to the 5′-OH of the pentose. Such a compound is called a nucleoside 5′-phosphate or a 5′-nucleotide. Such compound can be “5′-ribonucleotide” or “5′-deoxyribonucleotide.”

If only one phosphate group is attached to the 5′-carbon of the pentose, the structure is called as nucleoside monophosphate (NMP), like adenosine monophosphate (AMP) (also called adenylate). If a second or third phosphate is added to the nucleoside, a nucleoside diphosphate (for example, adenosine diphosphate ADP or triphosphate (for example, adenosine triphosphate, ATP results).