Lecture (1) Bc120

Nucleic acids
University of Tripoli, Faculty of Medicine
Department of Biochemistry and molecular biology
Dr: Fahima Alnagar

Biochemistry text books (these books are in my telegram channel)

• Harper’s biochemistry (31th ED).
• Lippincott’s illustrated reviews: biochemistry. Richard a. Harvey and denise r. Ferrier (6th ED).
• International edition of biochemistry (third edition). Mathews, van holde, and ahern

Spring 2023

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 Nucleic acids
Nucleic acids are polymers formed by attaching together monomers called nucleotides. There are two
important nucleic acids, DNA, which is the genetic material, and RNA, which is involved in using the
genetic information.
DNA and RNA are consisted of:
1. Phosphate

2) 5-carbon Sugars:
a) D-Ribose: is a five carbon sugar contained in ribonucleosides, ribonucleotides, and their
derivatives. (Note that D here refers to the D/L configuration, not "deoxy" as in deoxyribose).

b) Deoxyribose: (more accurately named 2-deoxyribose) is a five carbon sugar contained in

deoxyribonucleosides, deoxyribonucleotides, and their derivatives. Deoxyribose differs from ribose in
lacking a hydroxyl at position 2. Deoxyribonucleotides are the monomeric units (building blocks) of DNA.

3, Nitrogenous base:
a. There are 4 kinds of nitrogenous bases in DNA including.
b. The purine bases are referred to as A (Adenine) and G (Guanine).
c. The pyrimidine bases are T (Thymine) and C (cytosine).
**Note: In RNA there is a U base instead of the T.
Nitrogen bases: Purines and pyrimidines are nitrogen-containing heterocycles, cyclic compounds whose
rings contain both carbon and other elements (hetero atoms). Note that the smaller pyrimidine has the longer
name and the larger purine the shorter name and that their six-atom rings are numbered in opposite
directions

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 a. Purines:
• contains the heterocyclic ring system. Fusion of the pyrimidine ring with imidazole (5-membered ring)
yields the purine ring.
• The Purine bases present in nucleotides are Adenine and Guanine.

Adenine:
• Is a purine base found in DNA and RNA.
• In nucleosides and nucleotides, adenine is linked to the sugar moiety via a covalent bond between nitrogen
#9 of adenine and carbon #1 of the sugar.
• The ribonucleoside containing adenine is called adenosine.
• The deoxyribonucleoside containing adenine is called deoxyadenosine.
Guanine:
• Is a purine base found in DNA and RNA. In nucleosides and nucleotides, guanine is linked to the sugar
moiety via a covalent bond between nitrogen #9 of guanine and carbon #1 of the sugar.
• The ribonucleoside containing guanine is called guanosine. The deoxyribonucleoside
containing guanine is called deoxyguanosine.

b. Pyrimidines:
• It is 6 membered heterocyclic compound contains carbon, nitrogen, hydrogen and oxygen atoms.
• The C and N atoms are numbered in clockwise direction.
• The pyrimidine bases present in nucleotides are cytosine (C), uracil (U) and Thymine (T).

Cytosine:
• Is a pyrimidine base found in DNA and RNA. In nucleosides and nucleotides, cytosine is linked to the
sugar moiety via a covalent bond between nitrogen #1 of cytosine and carbon #1 of the sugar.
• The ribonucleoside containing cytosine is called cytidine.
• The deoxyribonucleoside containing cytosine is called deoxycytidine.

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Thymine:
• is a pyrimidine base found almost exclusively in DNA.
• In nucleosides and nucleotides, thymine is linked to the sugar moiety via a covalent bond between
nitrogen #1 in thymine and carbon #1 of the sugar.
• The deoxyribonucleoside containing thymine is called thymidine.
Uracil:
• Is a pyrimidine base found almost exclusively in RNA. In nucleosides and nucleotides, uracil is linked to
the sugar moiety via a covalent bond between nitrogen 1 in uracil and carbon 1 of the sugar.
• The ribonucleoside containing uracil is called uridine. The deoxyribonucleoside containing uracil is
called deoxyuridine.

Nucleosides:
• Deoxyribonucleosides or ribonucleosides are collectively called nucleosides.
• are named according to the base they contain.
• are composed of a base (adenine, guanine, cytosine, thymine, or uracil) attached to a sugar (ribose for
ribonucleosides or deoxyribose for deoxyribonucleosides).
• Corresponding to the bases above, common ribonucleosides are named adenosine, guanosine, cytidine,
and uridine, respectively. Common deoxyribonucleosides are named deoxyadenosine, deoxyguanosine,
deoxycytidine, deoxyuridine, and deoxythymidine, respectively.

Nucleotides
• Ribonucleotides and deoxyribonucleotides (collectively called nucleotides) are the building blocks of
the nucleic acids, RNA and DNA, respectively.
• Nucleotides are composed of a sugar, a phosphate, and a base.
• Nucleotides differ from nucleosides:
o in that the latter do not contain phosphate, so we sometimes refer to nucleotides as nucleoside mono, di,
or tri)-phosphates. For example, adenosine diphosphate is a nucleotide (also called ADP).
o Deoxyribonucleotides (written with a 'd') differ from ribonucleotides in containing deoxyribose as the
sugar moiety instead of ribose.

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• The table below lists the most common nucleotides found in the cells.

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ATP, its diphosphate, and its monophosphate Cyclic Adenosine Monophosphate (cAMP):
• cAMP is a second messenger that hormones act through binding to specific cellular receptors.
• Second messengers are often used to transmit the hormonal message to the target metabolic pathway.
• cAMP acts to stimulate the kinase cascade ).

• The bond joining the 1'-carbon of the deoxyribose sugar to the heterocyclic base is the N-glycosidic bond.
Rotation about this bond gives rise to Syn and Anti conformations. Rotation about this bond is restricted
and the anti-conformation is generally favored.
• Numerals with a prime (eg, 2′ or 3′) distinguish atoms of the sugar from those of the heterocyclic base.

Biological Functions of Nucleosides & Nucleotides

• Nucleotides are found primarily as the monomeric units comprising the major nucleic acids of the cell,
RNA and DNA Nucleotides have a variety of roles in cellular metabolism:
• Serving as energy stores for future use in phosphate transfer reactions. These reactions are predominantly
carried out by ATP.
• Forming a portion of several important coenzymes such as NAD+, NADP+, FAD and coenzyme A.
• They are the energy currency in metabolic reactions.
• The essential chemical links in the response of cells to hormones and other stimuli, and the structural
components of a variety of enzyme cofactors and metabolic intermediates.
Purine nucleotides serve as:
• Energy currency in cells in the form of ATP and GTP.
• Structural components of many enzyme cofactors or co-enzymes (e.g., NAD, NADP+, FAD, and
CoA.), cellular signal transduction (cAMP and cGMP as ‘second messengers’); and as a methyl
donor.
Pyrimidine nucleotides:
• Serve as high energy metabolic intermediates such as UDP in carbohydrates metabolism and CDP are
essential intermediates in the biosynthesis of phospholipids.
• Note: ATP, GTP, CDP, cAMP, NAD+, NADP+, FAD, coenzyme A (CoA), etc. are all examples of
nucleotides that are found in the body but are not part of DNA or RNA polynucleotide chains.

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 DNA (Deoxyribo Nucleic Acid):
• is called the genetic material because it contains the genetic information for every cell and tissue in an
organism.
• DNA is a component of the chromosomes (proteins are the other component). Deoxyribonucleotides
contain three components - a phosphate group, a modified sugar called deoxyribose, and a nitrogenous
base (adenine, guanine, cytosine, or thymine).
• DNA is a polymer of nucleoside monophosphates. The backbone of the chain consists of alternating
units of phosphate and sugar.
• The chain is said to be oriented 5' to 3' as it goes from top to bottom. That is, the phosphate residue is
attached to the hydroxyl on the 5' carbon of one sugar residue and the 3' hydroxyl of the next one.
• In cells, DNA consists of two strands wound around each other in a double-helical structure such that the
phosphate-deoxyribose backbone is on the outside and the bases are on the inside. The two strands in a
DNA molecule is opposite; that is, the 5' end of one strand matches up to the 3' end of the other strand.
Thus, the strands are said to be "antiparallel”.
• The arrangement of bases in double-stranded DNA is not random. Adenine on one strand is always
arranged adjacent to a thymine on the other strand A-T and vice-versa. Guanine is similarly paired with
cytosine G-C and vice-versa.
• Hydrogen bonds between the base pairs hold the two strands together. As Watson and Crick (discoverers
of the structure of DNA) noted, the complementary nature of the bases provides a reasonably simple means
for the molecule to be replicated because all of the information for making double-stranded DNA is
contained within one of the two strands.

The structure of DNA is a double-stranded, antiparallel helix

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 A-T base pairs have two connecting hydrogen bonds; G-C base pairs have three
Primary, secondary, tertiary structure of nucleic acids
1. The primary structure is the sequence of nucleoside monophosphates (usually written as the sequence of
bases they contain).
2. The secondary structure refers to the shape a nucleic acid assumes as a result of the primary structure. B-
DNA, A-DNA, and Z-DNA are forms of secondary structure.
B form: Most DNA is in the B form. This so-called B-DNA is a right-handed helix.

A form: A polynucleotide in the A form is a right-handed helix. The A form is found in double-
stranded RNA and in DNA-RNA hybrids.
Z form: Z-DNA is a left-handed helix found in polynucleotides with alternating purines and pyrimidines in
each strand, as in the following:
5'CGCGCG3'
3'GCGCGC5'

Z-DNA
3. Tertiary structure refers to large-scale folding in a linear polymer that is at a higher order
than secondary structure. The tertiary structure is the specific three-dimensional shape into
which an entire chain is folded.