Upload
others
View
11
Download
0
Embed Size (px)
Citation preview
Chemistry of Nucleosides, Nucleotides
& Nucleic acid
Dr.Almoeiz Yousif MS.c.,Ph.D.,MEE
Nucleosides
•Nucleosides composed only of base and sugar.
Frid
ay, A
pri
l 24
, 20
20
3
N. Base Sugar
Nucleotides
• nucleotides define as a monomer of Nucleic acids ( DNA & RNA).
• Nucleotides are intracellular molecules having the following structure:
Frid
ay, A
pri
l 24
, 20
20
4
N.Base Sugar Phosphate
Nitrogenous Bases
Frid
ay, A
pri
l 24
, 20
20
5
The nitrogenous bases are either purine or pyrimidine
Pyrimidine bases
•A pyrimidine bases -containing, a single six
membered ring.
•Numbering is clockwise
Frid
ay, A
pri
l 24
, 20
20
6
Pyrimidine bases
•There are three pyrimidines commonly found in
nucleic acids: Fr
iday
, Ap
ril 2
4, 2
02
0
7
Uracil
Thymine Cytosine
Frid
ay, A
pri
l 24
, 20
20
8
Uracil Thymine Cytosine
Pyrimidine bases
•The pyrimidines in DNA are cytosine (C) and thymine (T).
•The pyrimidines in RNA are cytosine ( C) and uracil (U).
•Cytosine can be found in DNA and RNA.
•Thymine is found only in DNA, while uracils are found only in RNA.
Frid
ay, A
pri
l 24
, 20
20
9
Purines
• Purines consist of linked five - membered and six- membered rings.
•Numbering is anticlockwise
Frid
ay, A
pri
l 24
, 20
20
10
Purines
•There are two purines commonly found in
Nucleic acids.
•Each can be found in nucleic acid.
Frid
ay, A
pri
l 24
, 20
20
11
Purines
• Other purine bases produce during metabolism, present in free state in cells:
1. Hypoxanthine.
2. Xanthine.
3. Uric acid. (end product of Adenine & Guanine catabolism)
Frid
ay, A
pri
l 24
, 20
20
12
Sugars
Frid
ay, A
pri
l 24
, 20
20
13
• The sugars enter in the nucleotides are Pentose sugars (5-Carbon sugars)
Sugars
Frid
ay, A
pri
l 24
, 20
20
15
• DNA and RNA have different sugars.
• RNA nucleotides or Ribonucleotides , contain ribose sugar
which have a hydroxyl group in both the 2, and 3 – position of
the sugar ring.
Sugars
Frid
ay, A
pri
l 24
, 20
20
16
• DNA nucleotides or deoxyribonucleotides have 2-
deoxyribose sugars.
•These sugars have only a single hydroxyl group in the 3
position of the sugar ring.
Phosphate Groups
• A nucleotide contain a single phosphate group, which is a strong acid that gives nucleic acids their acidity.
• Phosphates can be attached through the oxygen of the hydroxyl group of either C3 or C5 atoms of the sugar.
• It is more commonly attached to C5.
Frid
ay, A
pri
l 24
, 20
20
17
Nucleosides
• Result from linking one of the sugars with a purine or pyrimidine base through
an N-glycosidic linkage.
Frid
ay, A
pri
l 24
, 20
20
19
Nucleotides • Nucleotides are phosphorylated nucleosides
• Result from linking one or more phosphates with a nucleoside onto OH group 5’ end of the sugar.
Frid
ay, A
pri
l 24
, 20
20
20
Nucleosides and nucleotides
Naming Conventions
•Nucleosides:
•Purine nucleosides end in “-sine”
•Adenosine, Guanosine.
•Pyrimidine nucleosides end in “-dine”
• Thymidine, Cytidine, Uridine
Frid
ay, A
pri
l 24
, 20
20
22
Naming Conventions
•Nucleotides:
• Start with the nucleoside name from above and add “mono-”, “di-”, or “triphosphate”
•Adenosine Monophosphate, Cytidine Triphosphate, Deoxythymidine Diphosphate
Frid
ay, A
pri
l 24
, 20
20
23
Purine Base Nucleoside Nucleotide
Adenine (A) Adenosine Adenosine mono phosphate
(AMP, ADP,ATP)
Guanine (G) Guanosine Guanosine Mono P.
(GMP)
Xanthine Xanthosine Xanthosine Mono
Phosphate
Hypoxanthine Inosine Inosine Mono Phospate
Pyrimidine Base Nucleoside Nucleotide
Cytosine (C) Cytidine CMP
Uracil (U) Uridine UMP
Thiamine (T) Thymidine TMP
Functions of Nucleotides
1. They enter in the structure of nucleic acid, ( DNA , RNA).
2. Nucleoside Triphosphates are major biologic transducer of free energy (ATP,
GTP).
3. Important components of coenzymes
FAD, NAD+ and Coenzyme A.
4. Acts as a second messenger, (c-AMP, c GMP).
Frid
ay, A
pri
l 24
, 20
20
26
Functions of Nucleotides
5. UDP- glucoronic acid is donor for conjugation reactions
that form urinary glucornide conjugates for biluribin or
drugs as aspirin
6. Cytosine derivatives CTP, is involved in synthesis
ceramide.
Frid
ay, A
pri
l 24
, 20
20
27
Nucleic acid Chemistry
Friday, April 24, 2020 28
What Are Nucleic Acids?
• Nucleic acids are polynucleotides: linear polymers of nucleotides
linked 3 to 5 by phosphodiester bridges .
• They are formed as 5-nucleoside monophosphates
Frid
ay, A
pri
l 24
, 20
20
29
• Polymers of ribonucleotides are named ribonucleic acid, or RNA.
• Deoxyribonucleotide polymers are called deoxyribonucleic
• acid, or DNA.
Frid
ay, A
pri
l 24
, 20
20
30
Phosphodiester Bond
Frid
ay, A
pri
l 24
, 20
20
31
Base pairs
• In Nucleic acids, there is base pairing
• It’s a Complementarity (T=A, C=G)
• Purines always base-pair with pyrimidines
• Cytosine hydrogen bonds with guanine
• Thymine hydrogen bonds with adenine or uracil
• Due to distancing and proximity of unshared pairs and
hydrogens
Frid
ay, A
pri
l 24
, 20
20
32
GC base pair
Frid
ay, A
pri
l 24
, 20
20
33
N
N
N
NH
O
N HR
H
Guanine
NN
O
N
H
H
R
-- -- --
-- -- --
-- -- --
cytosine
3 H- bonds
AT base Pair
N
N
N
N
N H
H
R
adenine
NNH
O
O
R
-- -- --
-- -- -- --
thymine
2 H-bonds
Frid
ay, A
pri
l 24
, 20
20
34
Base Pairs
Frid
ay, A
pri
l 24
, 20
20
35
Pyrimidines
NH2
O
N
N NH
N
Guanine
N
N
Adenine
N
N
NH2
N O
NH2
N O
NH2
N
Cytosine
Purines
Uracil (RNA)
CH3
N O N
O
NH
N O N
O
NH
Thymine (DNA)
Frid
ay, A
pri
l 24
, 20
20
36
- +
+
+
-
-
Base Pairing Guanine And Cytosine
Frid
ay, A
pri
l 24
, 20
20
37
+
- Thymine
-
+ Adenine
Base Pairing Adenine And Thymine
Frid
ay, A
pri
l 24
, 20
20
38
Base Pairing Adenine And Cytosine
Frid
ay, A
pri
l 24
, 20
20
39
-
+
-
Base Pairing Guanine And Thymine
Frid
ay, A
pri
l 24
, 20
20
40
+
+
-
Frid
ay, A
pri
l 24
, 20
20
41
H
P
O
HO
O
O
CH2
H OH
P
O
O
HO
O
O
CH2
H
P
O
OH
HO
O
O
CH2
NH2
N
N
N
N
O
O
NH2 N
NH
N
N
N O
NH2
N
D
N
A Frid
ay, A
pri
l 24
, 20
20
42
O H
P
O
HO
O
O
CH2
HO
H
H
P HO
O
O
CH2
O
O
H
H2O
H OH
P
O
HO
O
O
CH2
H2O
5’Phosphate group
3’Hydroxyl group
5’Phosphate group
3’Hydroxyl group
Because of specific base paring, any single stranded sequence of DNA or RNA can be used as a template for production of the complimentary strand
DNA structure
• B-DNA is most common
• Antiparallel
• bases inside • Hydrophobic
• Perpendicular to helix
• stands complementary • Very important for information transfer
• Each strand a template for the other.
• right handed
• major and minor groove
Frid
ay, A
pri
l 24
, 20
20
43
Forms of DNA
Frid
ay, A
pri
l 24
, 20
20
44
Denaturation and Renaturation
• Heating double stranded DNA can overcome the hydrogen bonds
holding it together and cause the strands to separate resulting in
denaturation of the DNA
• When cooled relatively weak hydrogen bonds between bases can
reform and the DNA renatures
Frid
ay, A
pri
l 24
, 20
20
45 TACTCGACATGCTAGCAC ATGAGCTGTACGATCGTG
Double stranded DNA
TACTCGACATGCTAGCAC ATGAGCTGTACGATCGTG
Double stranded DNA TACTCGACATGCTAGCAC
ATGAGCTGTACGATCGTG
Denatured DNA
Single stranded DNA
RNA
• codes for protein
• no consistent secondary structure
• single stranded
• Ribose instead of deoxyribose
• Thymine (T) replaced by Uracil
Frid
ay, A
pri
l 24
, 20
20
46
47
. Three Types of RNA
•mRNA
• carries genetic information to the ribosomes
• rRNA
• , along with protein, makes up the ribosomes
• tRNA
• transfers amino acids to the ribosomes where proteins are synthesized
Frid
ay, A
pri
l 24
, 20
20
47
Frid
ay, A
pri
l 24
, 20
20
48
DNA versus RNA
Frid
ay, A
pri
l 24
, 20
20
49
DNA RNA
Double-stranded Single-stranded
Holds information Transfers information
A pairs with T A pairs with U (if paired)
C pairs with G C pairs with G (if paired)
Sugar is deoxyribose; lacks OH
at carbon 2
Sugar is ribose; has OH at
carbon 2
Frid
ay, A
pri
l 24
, 20
20
50