Nucleotides

and
Nucleic Acid

HISTORY
Albrecht Kossel (1853-1927), German
physiologist and Nobel laureate
In1879, Kossel focused his studies on nuclein,
a substance found within the nucleus of a
yeast cell.
Nucleic acids consist of nitrogen-bearing
compounds known as purines and
pyrimidines.
From these purines and pyrimidines, Kossel
and his colleagues isolated the nitrogencontaining bases cytosine, thymine, adenine,
and guanine

Medical significance of Nucleotide

Nucleotides make up nucleic acids (DNA and RNA)
Nucleotide triphosphates are the energy carriers
in cells
Many metabolic pathways are regulated by the
level of the individual nucleotides
Adenine nucleotides are components of many of
the coenzymes

Medical significance of nucleotide

Anticancer agents

Anti viral agents

What are Nucleotides?

Nucleotides are composed of:

Nitrogenous base
Pentose sugar
Phosphate groups

Nitrogenous Bases
Aromatic and heterocyclic
Two types:
Purine and Pyrimidine

Purines
Double cyclic ring
Adenine
Guanine

Adenine

Guanine

Structures of purine

Pyrimidines
Cytosine
Thymine.
Single cyclic

Uracil

Thymine

Cytosin
e

Structures of pyrimidine

Sugar
Pentoses (5-C sugars)
Numbering of sugars is primed.

Ribose

Deoxyribose

Phosphate Groups
Mono-, di- or triphosphates
Phosphates can be bonded to either
C2, C3 or C5 atoms of the sugar

Nucleosides
Sugar linkage with purine or pyrimidine base through an N-glycosidic linkage

PURINES

Nucleotides
Linking one or more phosphates with a
nucleoside

PHOSPHATE LINKAGE
In
5
3
2

Ribonucleotide
Phosphate
Phosphate
Phosphate

In Deoxyribonucleotide
5 Phosphate
3 Phosphate

Naming Conventions
Nucleosides:
Purine nucleosides end in -sine
Adenosine, Guanosine

Pyrimidine nucleosides end in -dine

Thymidine, Cytidine, Uridine

Nucleotides:
Start with the nucleoside name from above and
add mono-, di-, or triphosphate
Adenosine Monophosphate
Cytidine Triphosphate
Deoxythymidine Diphosphate

Formation of di, tri or

Polynucleotide

Chargraffs Rule:
Adenine and Thymine

always join together

A

Cytosine and Guanine

always join together

C

G
18

DERIVATIVES OF NUCLEOTIDE
AND THEIR IMPORTANCE
1-ADENINE
ATP, ADP, AMP
ATP is High energy carrier
ADP is part of coenzyme
cAMP involved in cell signaling
Oxidative Phosphorylation
2-GUANINE
GDP, GTP, GMP
Involve in Citric acid cycle
Protein Synthesis
Part of Membrane Receptor
Cyclic GMP act as messenger for certain
hormones

DERIVATIVES OF NUCLEOTIDE AND THEIR I

3URACIL
UDP
UDP-Glucose. Provide glucose during
glycogenesis
UDP-Glucuronic acid
4CYTOSINE
CTP/CDP
Take part in synthesis of lecithins

Nucleotides in DNA and

RNA
DNA
dAMP
dGMP
dCMP
dTMP
RNA
AMP
GMP
CMP
UMP

Deoxyadenosine monophosphate
Deoxyguanosine monophosphate
Deoxycytidine monophosphate
Deoxythymidine monophosphate

adenosine monophosphate
guanosine monophosphate
cytidine monophosphate
uridine monophosphate
21

TYPES OF NUCLEIC ACID

DEOXY RIBONUCLEIC ACID DNA

RIBO NUCLEIC ACID RNA
mRNA
tRNA
rRNA

Prokaryotic DNA

DNA Organization
Eukaryotic Cell

DNA structure
B-DNA, A-DNA , Z-DNA forms
B-DNA is most common
Antiparallel
stands complementary
right handed
major and minor groove

GC base pair
H
N
O -- -- -- H

NH -- -- --

N
R

O
N H -- -- --

N
R

H
Guanine

3 H- bonds

cytosine

AT base Pair
H
N H -- -- -- O

N
N
R

-- -- -- -- HN

N
adenine

O
thymine
2 H-bonds

N
R

Composition of Human
DNA
Purine

Pyrimidine

Adenine (A) 30.3% Thymine (T) 30.3%

Guanine (G) 19.5% Cytosine (C) 19.9%
Total purines: 49.8% Total pyrimidines:
50.1%

Double Helix Structure of DNA

Forms of DNA

Double Helix of DNA

32

RNA

codes for protein

single stranded
Ribose instead of deoxyribose
Thymine (T) replaced by Uracil

Roles of nucleic acids

DNA is carrier of genetic information
DNA contains genes, the information needed
to synthesize functional proteins and RNAs
DNA contains segments that play a role in
regulation of gene expression and cell
function
Ribosomal RNAs (rRNAs) are components of
ribosomes, playing a role in protein
synthesis
Messenger RNAs (mRNAs) carry genetic
information from a gene to the ribosome
3 Transfer RNAs (tRNAs) translate information
on mRNA into an amino acid sequence

Organization of Eukaryotic Chromosomes

36

37

38

Synthetic Nucleotide

Purine Bases (pu):

Major : (A)&(G)
Minor: Inosine(I) &
methyl guanine(7mG)
Unnatural :
Mercaptopurine

Allopurinol

Synthetic Nucleotide

Pyrimidines (py):
Major : (T), (C) & (U)
Minor: DHU , 5mC &
5hmC
Unnatural: Fluorouracil
(5FU)

DIGESTION OF NUCLEOPROTEINS
Nucleicacids (polynucleotides)
Nucleases in pancreatic juice,
phosphodiesterases in intestine
Mononucleotides
H2O
Nucleotidases
H3PO4
Nucleosides
H3PO4
Sugar Phosphate

Nucleosidases or
Nucleoside phosphorylases

Nitrogenous bases
(Purines and pyrimidines)

Disorders of Nucleotides
Disorder
Gout

Lesch Nyhan
syndrome
SCID
Orotic Aciduria

Defect
PRPP synthase/
HGPRT

lack of HGPRT

ADA
UMP synthetase

Purine Degradation
Purine Nucleotides from ingested nucleic
acids or turnover of cellular nucleic
acids is excreted by humans as uric acid
Humans excrete about 0.6 g uric acid
every 24 hours

X
Allopurinol

Degradation of Purine nucleotides

USE IN SALVAGE PTHWAY

GOUT

URIC ACID - 2.5-8 mg/dl MALES

1.5-6 mg/dl FEMALES
URIC ACID POOL - 1200 mg IN MALES
600 mg IN FEMALES
IN GOUT - 2000-4000 mg UP TO 31000 mg
TOPHI MONOSODIUM URATES - IN
JOINTS & TISSUE
COMPLICATIONS
STONE FORMATION
URIC ACID IS INSOLUBLE IN ACID MEDIUM
HYPERLIPEDEMIA

EXCRETION:

400-600 mg/24 HRS

Avoid:
Offal foods such as liver, kidneys, tripe, sweetbreads and tongue

Gout

ADENOSINE DEAMINASE
(ADA) DEFICIENCY
CAUSES SEVERE COMBINED
IMMUNODEFICIENCY (SCID) INVOLVING T-CELL
AND USUALLY B-CELL DYSFUNCTION
EXTREMELY LARGE BUILDUPS OF dATP IN RED
CELLS HAVE BEEN OBSERVED. (dATP IS AN
INHIBITOR OF RIBONUCLEOTIDE REDUCTASE,
AND THEREFORE, OF DNA SYNTHESIS)
ADA-DEFICIENT CHILDREN USUALLY DIE
BEFORE 2 YEARS OF AGE FROM
OVERWHELMING INFECTION.

Therapies for SCID

Can be diagnosed in infants through
a simple blood test (white cell count)
Bone marrow transplant for infants
Familial donor

Continued administration of
adenosine deaminase (ADA-PEG)
Gene therapy- repair defective gene
in T-cells or blood stem cells

Adenosine Deaminase (ADA) and

Purine Nucleoside Phosphorylase
(PNP) Deficiency

A deficiency of either ADA or PNP causes a

moderate to complete lack of immune
function
Affected children cannot survive outside a
sterile environment
They may also have moderate neurological
problems, including partial paralysis of the
limbs
When a compatible donor can be found, bone
marrow transplant is an effective treatment

Lesch-Nyhan Syndrome
Absence of HGPRTase
X-linked (Gene on X)
Occurs primarily in
males

Characterized by:

GoogleImages.com

Increased uric acid

Spasticity
Neurological defects
Aggressive behavior
Self-mutilation

Salvage Pathway for

Purines
Hypoxanthine
or
Guanine
Adenine

+ PRPP =IMPorGMP+PPi

Hypoxanthineguanosylphosphoribosyltransferase
(HGPRTase)

+ PRPP =AMP+PPi
Adeninephosphoribosyltransferase
(APRTase)

Anti-cancer drug
specifically block
dTMP production

Folic acid

CATABOLISM OF PYRIMIDINES

OROTIC ACIDURIA
Orotate phosphoribosyl transferase and OMP
decarboxylase are separate domains of a single
polypeptide
Low activities of orotidine phosphate
decarboxylase and orotate
phosphoribosyltransferase result in abnormal
growth, megaloblastic anemia, and the excretion
of large amounts of orotate in the urine
Feeding a diet rich in uridine results in
improvement of the anemia and decreased
excretion of orotate