nucleotide chemistry for medical students

1. Nucleotide chemistry

2. •Nucleotide = pentose +
base +phosphate
•Nucleoside = pentose +
base

3. Major bases
BASE NUCLEOSIDE NUCLEOTIDE
PURINES Adenine Adenosine AMP
Guanine Guanosine GMP
Oxopurines Hypoxanthine Inosine IMP
Xanthine xanthosine XMP
Pyrimidines Cytosine Cytidine CMP
Thymine Thymidine TMP
Uracil Uridine UMP

4. Minor bases
Base Use
Purines 7-methyl Guanine RNA
Caffeine (Coffee) • Diuretics
• CNS stimulators
• Doesn’t produce uric
acid
Theophylline(Tea)
Theobromine(cocoa)
pyrimidines Dihydrouracil
5-Methylcytosine
Uric acid: end product of purine catabolism
• excreted in urine
• level in blood is 3 to 7 mg/dL
• Gout is a disease characterized by high levels of
plasma uric acid (hyperuricemia).

5. Adenine nucleotides
1. AMP,ADP,ATP
– Storage of energy(2 high energy bonds 1.αβ 2.βγ)
2. cAMP
– 2ry messenger(ATP
adenylyl cyclase
cAMP
phoshodiesterase
AMP)
3. PAPS
– Sulphur containing compounds(1.GAGs 2.sulpholipids)

6. Adenine nucleotides
4. Coenzymes
a) Hydrogen carriers
I. NAD & NADP
II. FAD
b) Acyl group carrier
I. Coenzyme A (coA)
N.B
• FMN is a hydrogen carrier that doesn’t contain Adenine
• S-Adenosyl methionine (Active Methionine) or (SAM) is a
nucleoside and methyl donor

7. Guanine Nucleotides
1. GMP, GDP, GTP
2. cGMP
– 2ry messenger(GTP
gyaneylyl cyclase
cGMP
phoshodiesterase
GMP)
– may be antagonistic to cAMP.
– vasodilators (smooth muscle relaxation )
– nitric oxide.

8. Cytosine Nucleotides
1. CMP, CDP, CTP
2. CDP-choline, CDP-ethanolamine or CDP-
diacylglycerol
– Phospholipid synthesis

9. Uracil Nucleotides
• UMP, UDP, UTP
a) - UDP-Glc is used for synthesis of glycogen,
glycoproteins and glycolipids.
b) - UDP-Gal is used for synthesis of lactose,
glycoproteins and glycolipids.
c) - UDP-glucuronic acid
– active form of glucuronic acid
– synthesis of GAGs
– conjugation reactions with steroids, bile pigments and
some drugs.

10. 2ry Messengers
cAMP DAG &IP3

11. 2ry Messengers
DAG &IP3
1. activation of G proteins
2. activation of phospholipase C.
3. PIP2
phospholipase C
DAG+IP3
4. IP3 Calcium
5. DAG and Caicium activates protein
kinase C (PKC)
6. phosphorylation of certain proteins.
• Examples
1. chemical transmitters acetylcholine,
histamine and serotonin),
2. hormones vasopressin and α-1 receptors
3. growth factors
cAMP
1. activation of G proteins
2. activation of adenylyl cyclase cAMP
3. activates the protein kinase A
4. phosphorylation of proteins
5. It can be reversed by
a) Phosphatase (dephosphorelation)
b) Phophodiesterase( cAMP )
6. Examples insulin&glucagon

12. Nucleic acid
chemistry

13. Genetic Terminology
1- Genes:
Classically a gene is a unit of the DNA that encodes a particular protein or RNA
molecule.
Chemically, a gene is a sequence of nucleotides along a DNA molecule.
Most eukaryotic genes are discontinuous i.e. coding sequences (exons or
expressed sequences) separated by noncoding sequences (introns).
2- Chromosomes:
Chromosomes : genes which are arranged in linear orders
Locus of the gene : is the position of a gene along a chromosome
Each cell contains two copies of each type of chromosomes (one inherited from
the mother and one inherited from the father).

14. Genetic Terminology
3-genome:
It is the total genetic information presented by the group of chromosomes in any cell.
The human haploid genome consists of 23 chromosomes with a total of three billion base pairs
(3 x 109 bp), contains about 30,000 to 50,000 genes.
4- genotype and phenotype:
The genotype is the set of genes in our DNA which is responsible for a particular trait.
The phenotype is the physical or biochemical expression of that trait. E.G. Skin color, hair color,
height, weight, behavior and some diseases like diabetes mellitus.
Homozygous: if the two genes (alleles) at certain locus in an individual are identical
Heterozygous. If the two genes are different from each other.

16. DNA

17. I- DNA Primary Structure:
• The nucleotides are linked together by phosphodiester bonds,
• Free phosphate group attached to 5`-hydroxyl group, free 3`- hydroxyl
group.
• The order of nucleotides in any DNA strand is always written in the 5`
to 3` direction.

18. II- DNA Secondary Structure : Double
Helix (dsDNA)
• Two antiparallel strands form a right-handed helix.
• Complementary base pairing : if Adenine is 20% then Cytosine is ???
• Base stacking :
– hydrogen bonding between complementary base pairs
– Van der Waals forces and hydrophobic interactions of stacked base pairs provide
the stability of the double helix.
• Dimensions
– The B-form of DNA is 2 nm wide.
– major groove (2.2 nm)
– minor groove (1.2 nm).

19. Denaturation of DNA
• Heating of DNA produces rupture of hydrogen bonds
and separation of the two strands of DNA or DNA
denaturation.
• Cooling of denatured DNA results in reformation of
the double helix or renaturation or reannealing.

20. DNA Tertiary Structures
• Supercoiling may be positive (more tight) or
negative (less tight).
• Negative supercoils are more commonly present
under normal physiological state.

21. DNA Tertiary Structures
Linear Circular
Site Eukaryotes Prokaryotes
Mitochondria in
eukaryotes
Types of supercoiling a) Toroidal: The DNA
may coil into a series of
spirals around a
cylinder-shaped object.
b) Interwound coil:
The DNA may also
cross over and under
itself repeatedly.
a) Right-handed
supercoil.
b) Left-handed
supercoil.

22. Structure of chromatid:
• 1- A single DNA molecule
• 2- Histone proteins
– 5 main types (H1, H2A, H2B, H3 and H4)
– +ve charged rich in lysine & arginine
– In contact with minor groove in DNA
• N.B chromatid is formed of many nucleosomes.
– nucleosome is formed of:
1. 8 histone ptns (2 copies of H2A, H2B, H3 and H4)
2. 1¾ toroidal supercoiled DNA segment (contains average 140 bp).
3. Linker or spacer DNA (contains average 60 bp)
4. H1is attached to linker DNA.

23. Structure of chromatid:
• 3- Non-histone proteins:
– They interact with the major groove
– Function :
a) important for regulation of gene expression
b) responsible for replication and transcription.
• Kinetochore : centromere(rich in A…T Bases) connected to specific
proteins.
– Connected to mitotic spindle
• Telomere

24. Supercoiling of DNA
• The length of human DNA per cell is
approximately 2 meters, and
• Diameter of the nucleus is 10 microns.
• Structure about 10 micron long and 1 micron
diameter

25. Mitochondrial DNA (mtDNA)
• 0.3 to 1% of the total cellular DNA.
• responsible for controlling synthesis of 2 rRNA, 22 tRNA and 13
proteins.
• proteins are involved in oxidative phosphorylation (electron transport
chain and ATP synthesis).
• maternally inherited
• certain types of myopathies.

26. RNA

27. A) Transfer RNAs (tRNAs)
• Smallest
• 15% percent of the total RNA
• Unusual bases (e.g. Dihydrouracil) this leads to
characteristic secondary and tertiary structure
(clover leaf appearance).
• Carries its specific amino acid to the site of protein
synthesis.

28. Transfer RNA is coiled to form a cloverleaf
appearance with five main arms:
1- The acceptor arm:
It terminates at its 3`OH end by a specific sequence formed of CCA.
It carries the amino acid
2- D arm:
It contains the unusual base dihydrouracil.
D-arm is important for recognition of tRNA by aminoacyl-tRNA
synthetase enzyme which catalyzes binding of a specific amino acid to
its specific tRNA.

29. Transfer RNA is coiled to form a cloverleaf
appearance with five main arms:
3- Anticodon arm:
It contains three specific bases known as the anticodon.
This portion of tRNA plays a key role in translation by pairing with the
complementary codon of mRNA and helps in placing each amino acid in
its proper site in the polypeptide chains of proteins.
4- Extra arm:
It contains from 3 to 12 bases and it is the major site for variation in
tRNA.

30. Transfer RNA is coiled to form a cloverleaf
appearance with five main arms:
5- TψC arm (or loop IV) contains the
unusual specific sequence of thymine
and pseudouridine bases.
Pseudouridine (C1` of ribose
attached to C5 of uracil)
This arm is important for binding of
tRNA to the ribosome during the
process of protein synthesis.

31. B) Messenger RNAs (mRNAs)
• 5% of the RNA
• It consists of:
1. Coding region
a) Initiation codon
b) Coding area
c) Stop codon
2. Non coding region
a) 5 Cap
b) Poly A tail

32. B) Messenger RNAs (mRNAs)
- Monocistronic mRNA: It carries information from just
one gene. It contains one initiation codon and one
termination codon and is characteristic of eukaryotes.
- Polycistronic mRNA: It contains multiple initiation and
multiple termination codons and is characteristic of
prokaryotes

33. C)Ribosomal RNAs (rRNAs)
In prokaryotic cells.
The fully active 70S ribosomes :
1. 50S subunit
2. 30S subunit.
The rRNA forms about 80% of total RNA of the cell.
Svedberg unit (sedimentation or S unit) is a measure of the
sedimentation velocity by high speed centrifuge, which depends on the
molecular weight as well as the size of the particles i.e. particle density.

34. C)Ribosomal RNAs (rRNAs)
In Eukaryotic cells
The fully active 80S ribosomes
60S subunit
a) 5S RNA
b) 5.8S RNA
c) 28S RNA
d) 50 proteins
40S subunit
a) 18S RNA.
b) 30 proteins.

35. D) Other Forms of RNA (Noncoding
RNA):
• In addition to the major three types of RNA, small
RNA species are found in eukaryotic cells. They
include:
1. - Small nuclear RNAs (snRNAs): It is involved in
mRNA processing.
2. - Micro RNAs (miRNAs): It plays an important role
in regulation of gene expression.

37. Prokaryotic DNA and Chromosomes
• Prokaryotic organisms include bacteria and blue-green algae. Each
cell contains one single double-stranded supercoiled circular
chromosome and has no nuclear membrane.
• The chromosome is associated with histone-like proteins.
• Plasmid DNA carries genetic information and undergoes replication
that may or may not be synchronized to chromosomal division.
• Plasmids may carry genes that convey antibiotic resistance to the
host bacterium.