Nucleotides and Nucleic Acids

Learning objectives:
Define and classify nucleotides and nucleoside. Define and classify nucleic acids. Differentiate between the types of RNA and the role of each one. Discuss the functions of important nucleotides.

Selected References
General, Organic and Biochemistry; 5th edition, Denniston et al., 2007; McGraw-Hill, New York. Chapter 20, Page: 667 674. Biochemistry 5th edition, Stryer et al., Chapter 5, Page: 117 125. The medical Biochemistry home page @ http://themedicalbiochemistrypage.org/nucleic-acids.html Nucleotide Structure wikipedia @ http://en.wikipedia.org/wiki/Nucleotide Nucleic acid Structure wikipedia @ http://en.wikipedia.org/wiki/Nucleic_acid The Structure of Nucleic Acids @ http://www.vivo.colostate.edu/hbooks/genetics/biotech/basics/na struct.html

Lecture outlines
Introduction Nucleotide structure
Nitrogenous bases Pentose sugar Phosphate group

Nucleotides in DNA and RNA Structure of Nucleic Acids

NUCLEOTIDES
Nucleotides may be considered one of the most important metabolites of the cell. Nucleotides are the building units of the nucleic acids of the cell, RNA and DNA. They also are required for numerous other important functions within the cell.

Question
What are the important derivatives of

nucleotides and what are their functions? What are the types of RNA and what is the role of each one?

NUCLEIC ACIDS
A nucleic acid is a macromolecule composed of chains of monomeric nucleotide. In biochemistry these molecules carry genetic information within cells. The most common nucleic acids are:
DNA: deoxyribonucleic acid RNA: ribonucleic acid (e.g., some viruses)

NUCLEIC ACIDS
Consist of chemically linked sequences of nucleotides
Nitrogenous base Pentose sugar 5-carbon (ribose or deoxyribose) Phosphate group
Base PO4

Sugar

Phoshate group

Nucleosides

= Nucleotides

Nitrogenous Bases
Two types of bases: Purines are fused five- and six-membered rings

Pyrimidines are six-membered rings

Purine Bases

H Adenine, A DNA & RNA Guanine, G

Pyrimidine Bases

H Cytosine, C RNA

H Uracil, U DNA

H Thymine, T

Nitrogenous Bases
Purines
Adenine Guanine A G DNA DNA RNA RNA

Pyrimidines
Cytosine Thymine Uracil C T U DNA DNA ------RNA -----RNA

Sugars
HOCH2 O OH HOCH2 O OH

OH ribose

OH

OH

(no O)

deoxyribose

RNA

DNA

Nucleosides in RNA
Base Adenine (A) Guanine (G) Cytosine (C) Uracil (U) Sugar ribose ribose ribose ribose Nucleoside Adenosine Guanosine Cytidine Uridine

Nucleosides in DNA
Base Adenine (A) Guanine (G) Cytosine (C) Thymine (T) Sugar Deoxyribose Deoxyribose Deoxyribose Deoxyribose Nucleoside Deoxyadenosine Deoxyguanosine Deoxycytidine Deoxythymidine

Nucleotide
Phosphate group + Nucleosides = Nucleotides

Example

Nucleotides in RNA and DNA

RNA AMP GMP CMP UMP DNA dAMP dGMP dCMP dTMP adenosine monophosphate guanosine monophosphate cytidine monophosphate uridine monophosphate

Deoxyadenosine monophosphate Deoxyguanosine monophosphate Deoxycytidine monophosphate Deoxythymidine monophosphate

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Structure of Nucleic Acids

Polymers of four nucleotides Linked by alternating sugar-phosphate bonds RNA: ribose and A, G, C, U DNA: deoxyribose and A,G,C,T
base base base base

sugar

sugar

sugar

sugar

nucleotide

nucleotide nucleotide nucleotide

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Nucleic Acid Structure

3,5-phosphodiester bond

Nucleic Acid Structure

NH 2 N CMP O O
-

O O CH 2 O

N
-N-glycosidic bond

P O
-

NH 2 OH N N O N N AMP

3,5-phosphodiester bond

O O P O
-

5 O CH 2

OH

Structure of Nucleic Acids

base base base

sugar

sugar

sugar

5p

OH3

DNA: Helix

3 5 3 5

DNA is double-stranded (two strands of nucleotides). The strands run in opposite directions (antiparallel).
5p 3OH
OH3

p5

Complementary Base Pairs

In the DNA double helix, purines and pyrimidines face each other The two polynucleotide chains in the double helix are connected by hydrogen bonds between the bases (maintain and hold the double-helix structure) Watson-Crick base-pairing rules A G T C

Hydrogen Bonds
H H H C C C N C O H H H N C C N C O N H C N H N C H N H O C C C N N C H C N H O H N C N C N C C N H N C H

Thymine
H

Adenine

Cytosine
H

Guanine

Complementary Base Pairs

Two H bonds for A-T Three H bonds for G-C

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Double Helix of DNA

3 5 3 5

Double-stranded (ds) DNA takes the form of a right handed helix with approximately 10 base pairs per turn of the helix.

Double Helix of DNA

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Complementary Base Pairs

Since one strand of DNA is complementary to the other, genetic material can be accurately

reproduced; each strand serves as the template for the synthesis of the other

Question
Write the complementary base sequence for the matching strand in the following DNA section:
-A-G-T-C-C-A-A-T-G-C-

Answer
Write the complementary base sequence for the matching strand in the following DNA section:
-A-G-T-C-C-A-A-T-G-C-

-T-C-A-G-G-T-T-A-C-G-

RNA Structure
RNAs are usually single stranded. Many RNA molecules have secondary structure in which intramolecular loops are formed by complementary base pairing.

RNA Structure
Base pairing in RNA follows exactly the same principles as with DNA: the two regions involved in duplex formation are antiparallel to one another, and the base pairs that form are A-U and G-C.

Question
What are the types of RNA and what is the role of each one? What are the important derivatives of nucleotides and what are their functions?

important functions of nucleotides

These functions include: 1. serving as energy stores for future use in phosphate transfer reactions. These reactions are predominantly carried out by ATP. 2. forming a portion of several important coenzymes such as NAD+, NADP+, FAD and coenzyme A. 3. serving 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.

important functions of nucleotides

4. controlling numerous enzymatic reactions through allosteric effects on enzyme activity. 5. serving as activated intermediates in numerous biosynthetic reactions. These activated intermediates include S-adenosylmethionine (S-AdoMet) involved in methyl transfer reactions as well as the many sugar coupled nucleotides involved in glycogen and

glycoprotein synthesis.

Adenosine Derivatives
The most common adenosine derivative is the cyclic form, 3'-5'-cyclic adenosine monophosphate, cAMP. This compound is a very powerful second messenger involved in passing signal transduction events from the cell surface to internal proteins, e.g. cAMP-dependent protein kinase (PKA). PKA phosphorylates a number of proteins, thereby, affecting their activity either positively or negatively.

Adenosine Derivatives
Cyclic-AMP is also involved in the regulation of ion channels by direct interaction with the channel proteins, e.g. in the activation of odorant receptors by odorant molecules. Formation of cAMP occurs in response to activation of receptor coupled adenylate cyclase. These receptors can be of any type, e.g. hormone receptors or odorant receptors.

Adenosine Derivatives
S-adenosylmethionine is a form of "activated" methionine which serves as a methyl donor in methylation reactions and as a source of propylamine in the synthesis of polyamines.

Guanosine Derivatives
A cyclic form of GMP (cGMP) also is found in cells involved as a second messenger molecule. 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.

Any ? ? Questions ? ? ?