heterocyclic compound

1. 27.23
Pyrimidines and Purines

2. Pyrimidines and Purines
In order to understand the structure and
properties of DNA and RNA, we need to look at
their structural components.
We begin with certain heterocyclic aromatic
compounds called pyrimidines and purines.

3. Pyrimidines and Purines
Pyrimidine and purine are the names of the
parent compounds of two types of nitrogen-
containing heterocyclic aromatic compounds.
N
N
N
N
N
N
H
Pyrimidine Purine

4. Important Pyrimidines
Pyrimidines that occur in DNA are cytosine and
thymine. Cytosine and uracil are the
pyrimidines in RNA.
HN
N
H
O
O
Uracil
HN
N
H
O
O
CH3
Thymine
HN
N
H
NH2
O
Cytosine

5. Important Purines
Adenine and guanine are the principal purines
of both DNA and RNA.
Adenine
N
N
NH2
N
N
H
Guanine
O
HN
N
H
N
N
H2N

6. Caffeine and Theobromine
Caffeine (coffee) and theobromine (coffee and
tea) are naturally occurring purines.
Caffeine
N
N
O
N
N
H3C
O
CH3
CH3
Theobromine
O
HN
N
N
N
CH3
CH3
O

7. 27.24
Nucleosides

8. Nucleosides
The classical structural definition is that a
nucleoside is a pyrimidine or purine N-glycoside
of D-ribofuranose or 2-deoxy-D-ribofuranose.
Informal use has extended this definition to
apply to purine or pyrimidine N-glycosides of
almost any carbohydrate.
The purine or pyrimidine part of a nucleoside is
referred to as a purine or pyrimidine base.

9. Uridine and Adenosine
Uridine and adenosine are pyrimidine and purine
nucleosides respectively of D-ribofuranose.
Uridine
(a pyrimidine nucleoside)
Adenosine
(a purine nucleoside)
O
N
HOCH2
HN
O
OH
HO
O
N N
N N
HOCH2 O
OH
HO
NH2

10. 27.25
Nucleotides

11. Nucleotides
Nucleotides are phosphoric acid esters of
nucleosides.

12. Adenosine 5'-Monophosphate (AMP)
Adenosine 5'-monophosphate (AMP) is also called 5'-
adenylic acid.
N N
N N
O
OH
HO
NH2
OCH2
P
HO
O
HO

13. Adenosine 5'-Monophosphate (AMP)
Adenosine 5'-monophosphate (AMP) is also called 5'-
adenylic acid.
N N
N N
O
OH
HO
NH2
OCH2
P
HO
O
HO
1'
2'
3'
4'
5'

14. Adenosine Diphosphate (ADP)
N N
N N
O
OH
HO
NH2
OCH2
P
O
O
HO
P
O
HO
HO

15. Adenosine Triphosphate (ATP)
N N
N N
O
OH
HO
NH2
OCH2
P
O
O
HO
P
O
HO
O
P
O
HO
HO

16. ATP Stores Energy
AMP
ADP
ATP
Each step is endothermic.
Energy for each step comes
from carbohydrate metabolism
(glycolysis).
Reverse process is exothermic
and is the source of biological
energy.
DG° for hydrolysis of ATP to
ADP is –35 kJ/mol

17. Adenosine 3'-5'-Cyclic Monophosphate
(cAMP)
Cyclic AMP is an important regulator of many
biological processes.
N N
N N
O
OH
O
NH2
CH2
P
O
HO
O

18. 27.26
Nucleic Acids

19. Nucleic Acids
Nucleic acids are polymeric nucleotides
(polynucleotides).
5' Oxygen of one nucleotide is linked to the 3'
oxygen of another.

20. Fig. 27.22
A section of a
polynucleotide
chain.

21. 27.27
Structure and Replication of DNA:
The Double Helix

22. Composition of DNA
Erwin Chargaff (Columbia Univ.) studied DNAs
from various sources and analyzed the
distribution of purines and pyrimidines in them.
The distribution of the bases adenine (A),
guanine (G), thymine (T), and cytosine (C)
varied among species.
But the total purines (A and G) and the total
pyrimidines (T and C) were always equal.
Moreover: %A = %T, and %G = %C

23. Composition of Human DNA
Adenine (A) 30.3% Thymine (T) 30.3%
Guanine (G) 19.5% Cytosine (C) 19.9%
Total purines: 49.8% Total pyrimidines: 50.1%
For example:
Purine Pyrimidine

24. Base Pairing
Watson and Crick proposed that A and T were
equal because of complementary hydrogen
bonding.
2-deoxyribose
2-deoxyribose
A T

25. Base Pairing
Likewise, the amounts of G and C were equal
because of complementary hydrogen bonding.
2-deoxyribose
2-deoxyribose
G C

26. The DNA Duplex
Watson and Crick proposed a double-stranded
structure for DNA in which a purine or
pyrimidine base in one chain is hydrogen
bonded to its complement in the other.

27. Fig. 27.24
Two antiparallel
strands of DNA
are paired by
hydrogen bonds
between purine
and pyrimidine
bases.

28. Fig. 27.25
Helical structure of
DNA. The purine
and pyrimidine
bases are on the
inside, sugars and
phosphates on the
outside.

29. Fig. 27.26 DNA Replication
C
G
T
A
As the double helix
unwinds, each strand acts
as a template upon which
its complement is
constructed.

30. Fig. 27.26 DNA Replication
A
C
G
T
T'
A'
G'
C'

31. 27.28
DNA-Directed Protein Biosynthesis

32. DNA and Protein Biosynthesis
According to Crick, the "central dogma" of
molecular biology is:
"DNA makes RNA makes protein."
Three kinds of RNA are involved.
messenger RNA (mRNA)
transfer RNA (tRNA)
ribosomal RNA (rRNA)
There are two main stages.
transcription
translation

33. Transcription
Transcription is the formation of a strand of
mRNA using one of the DNA strands as a
template.
The nucleotide sequence of the mRNA is
complementary to the nucleotide sequence of
the DNA template.
Transcription begins at the 5' end of DNA and is
catalyzed by the enzyme RNA polymerase.

34. Transcription
A G G T C A C T G
T C C A G T G A C
A
T
G
C
T
T
T
T
T
T
C
C
C
C
C
A
A
A
A
A
G
G
A
G
G
G
As double-stranded DNA
unwinds, a complementary
strand of mRNA forms at the 5'
end.
5'
3'

35. Transcription
A G G T C A C T G
T C C A G T G A C
A
T
G
C
T
T
T
T
T
T
C
C
C
C
C
A
A
A
A
A
G
G
A
G
G
G
A
A
G
G
U
C
5'
3'
Uracil is incorporated in RNA
instead of thymine.

36. Translation
The nucleotide sequence of mRNA codes for
the different amino acids found in proteins.
There are three nucleotides per codon.
There are 64 possible combinations of A, U, G,
and C.
The genetic code is redundant. Some proteins
are coded for by more than one codon.

37. Table 27.4: mRNA Codons
Alanine Arginine Asparagine Aspartic Acid Cysteine
GCU GCA CGU CGA AAU GAU UGU
GCC GCG AGA CGC AAC GAC UGC
CGG AGG
Glutamic acid Glutamine Glycine Histidine Isoleucine
GAA CAA GGU GGA CAU AUU AUA
GAG CAG GGC GGG CAC AUC
Leucine Lysine Methionine Phenylalanine Proline
UUA CUU AAA AUG UUU CCU CCA
CUA UUG AAG UUC CCC CG
CUC CUG
Serine Threonine Tryptophan Tyrosine Valine
UCU UCA ACU ACA UGG UAU GUU GUA
AGU UCC ACC ACG UAC GUC GUG
UCG AGC

38. Transfer tRNA
There are 20 different tRNAs, one for each
amino acid.
Each tRNA is single stranded with a CCA triplet
at its 3' end.
A particular amino acid is attached to the tRNA
by an ester linkage involving the carboxyl group
of the amino acid and the 3' oxygen of the
tRNA.

39. Phenylalanine tRNA

40. Phenylalanine tRNA OCCHCH2C6H5
NH3
+
O
A
C
C
A A A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
C C
C
C
C
C
C
C
C C
C
C
U
U
U U
U
U
U
U
U
U
U
G
G
G
G G
G
G
G
G
G
G
G
U
G G
G
G
C
This AAA triplet is
complementary to a
UUU triplet
of mRNA; it is an
anticodon.

41. 27.29
DNA Sequencing

42. DNA Sequencing
Restriction enzymes cleave the polynucleotide
to smaller fragments.
These smaller fragments (100-200 base pairs)
are sequenced.
The two strands are separated.

43. DNA Sequencing
Single stranded DNA divided in four portions.
Each tube contains adenosine, thymidine,
guanosine, and cytidine plus the triphosphates
of their 2'-deoxy analogs.
POCH2
OH
O
O
O
OH
P
O
OH
P
O
HO base
H
HO
O

44. DNA Sequencing
The first tube also contains the 2,'3'-dideoxy analog of
adenosine triphosphate (ddATP); the second tube the
2,'3'-dideoxy analog of thymidine triphosphate (ddTTP),
the third contains ddGTP, and the fourth ddCTP.
POCH2
OH
O
O
O
OH
P
O
OH
P
O
HO base
H
H
O

45. DNA Sequencing
Each tube also contains a "primer," a short
section of the complementary DNA strand,
labeled with radioactive phosphorus (32P).
DNA synthesis takes place, producing a
complementary strand of the DNA strand used
as a template.
DNA synthesis stops when a dideoxynucleotide
is incorporated into the growing chain.

46. DNA Sequencing
The contents of each tube are separated by
electrophoresis and analyzed by
autoradiography.
There are four lanes on the electrophoresis gel.
Each DNA fragment will be one nucleotide
longer than the previous one.

47. Figure 27.29
T
TG
TGA
TGAC
TGACA
TGACAT
TGACATA
TGACATAC
TGACATACG
TGACATACGT
ddA ddT ddG ddC
Sequence of
fragment

48. Figure 27.29
T
TG
TGA
TGAC
TGACA
TGACAT
TGACATA
TGACATAC
TGACATACG
TGACATACGT
ddA ddT ddG ddC
A
AC
ACT
ACTG
ACTGT
ACTGTA
ACTGTAT
ACTGTATG
ACTGTATGC
ACTGTATGCA
Sequence of
fragment
Sequence of
original DNA