MEDICAL UNIVERSITY - PLOVDIV

PROGRAMME IN HUMAN BIOLOGY :

60 h. lecture courses
40 h. practical courses

modules :
. Molecular, Cell and General
Biology
. Parasitology
. Immunology

Head of department and lecturer

Prof. Victoria SARAFIAN, MD, PhD, DMSci
 Final mark in Biology mean of:
Colloquium in
MOLECULAR, CELL
AND GENERAL
BIOLOGY FINAL EXAM IN JUNE
First term/semester IMMUNOLOGY
Colloquium in + one or two of the
PARASITOLOGY modules which have not
+ practical exam been successfully passed
Second semester
 Marks
A - corresponds to Excellent performance 5.50 6.00
B Very good 4.50 5.49
C Good 3.50 4.49
D Passabe 3.00 3.49
E Failed 2.00 2.99

email: sarafian_for_students@abv.bg

www.medbiology.meduniversity-plovdiv.bg
 Public defense on Biology topics
Registration:
- Application for preparing a presentation till January 15,
2016 ; written text up to two A4 pages sent via email to:
biology.mu.plovdiv@gmail.com
Main point:
The best texts after selection are permitted to public
defense at the beginning of May 2016
Oral presentation for 5 min.
Bonus 1.00 to the final mark obtained at the final exam in
June
The list of topics and instructions for the defense are
available on the web-site
 NUCLEIC ACIDS

Prof. Victoria Sarafian, MD, PhD, DMedSci

Heterocyclic bases
Purines , G \bicyclic\ Structure of Nucleotide
Pyrimidines C, , U Nucl.acids
\monocyclic\
5 base
purine pyrimidine -4
Bases:
base

covalent
phosphodiester bond

3 -

Repeat
unit=nucleotide
covalent base + pentose
N-glycosylic bond
+ phosphoric acid
Nucleoside Nucleotide
(nucleoside phosphate, esterification
base, linked to pentose of of nucleoside)
(uridine, adenosine, guanosine, 5 base
cytidine, thymidine). After -4
phosphorylation (kinases)
transformed into nucleotides. base
Digested by nucleosidases to
base & pentose

purine 3 -
pyrimidine

N-glycosylic bond
 Physiological role of
adenosine
local hormone;
circulates in blood, binds
to specific receptors;
regulates the diameter of
blood vessels, smooth
muscular activity. - ,
muscle contractions, vasodilatation, 2
liberation of
Adenocard blocks electrical
neurotransmitters, lipid impulses form the AV node - cAMP,
metabolism K-flow outside the cell
protects cells from stress Awakeness - extracellular as a result
and tissue injury of brain activity, sleepiness
improves local Facilitates falling asleep and inhibits
regeneration of diabetic awakening. The level of at every
hour after awakening
wounds
Sleep - ; caffeine blocks the binding
of to neuronal receptors, competes
for the same receptors ?
 5 phosphate end
Polar structure
negative charge
5 3-5 end of
PENTOSE!
Highly negatively
charged polymers!

nucleotide

3
3 hydroxyl end
 D NA
P P
H
Deoxy
ribose
NH2 CO T
Deoxy
ribose

P P

Deoxy
H Deoxy
ribose C CO NH2 G ribose

P Chemical bonds? P
Stacking interactions Base + sugar glycosylic
Negative sugar-phosphate Base + base b/n chains H-bond
backbone in the outside; bases Sugar + sugar b/n nucleotides
in the inside phosphodiester
 Structure of nucleic acids
Primary Secondary Tertiary

Linear
Bending in space
arrangement of Double helix with - conformation
monomers complementary
linked bases
Helicoidal model of DNA right-handed double helix

+ regulatory proteins
Small groove Large groove

Antiparallel run

1chromosome = 1 mol. DNA = 12 cm

DNA of each chromosomes in 1 nucleus (2-3 ) = 2 m
Chargaff rules:
1. A=T
G=C
Equal in all biological
species

A=30.9%
T=29,4%
G=19,9%
C=19,8%

2. Purines = Pyrimidines
Specific for each biological
species!
 Helicoidal model of DNA =
conformation = Watson-Crick model
1. Double stranded
2. Helicoidal
3. Antiparallel
4. pentose-phosphate backbone - polarity
5. Bases perpendicular to the axis
6. -bonds between the bases
7. Diameter 2 nm
8. Complementarity purines against
pyrimidines
9. - 2 -bonds; G-C 3 -bonds
10. Small and large groove
11. Turn of the helix 10 bp/turn
 1000 13
denaturation

renaturation 650

Types of nucleotide sequences depending on their

renaturation kinetics :
highly repetitive DNA sequences short seq. \5-100 nucl.\,occur in
thousands to 1 million copies; centromers, telomers, junk
moderately repetitive DNA sequences longer seq. \150-300
nucl.\,occur in 1 000 to 100 000 copies, evenly dispersed; histones,
rRNA, tRNA
unique DNA sequences coding seq. for structural genes \up to 1400
bp\, occur in 1-2 copies; 1-3% of the genome; all proteins except the
histones
DNA palindrome - a nucleotide sequence in one of the DNA
strands which in the 5-3 direction is read in the same way as the
opposite sequence in the complementary DNA strand in the 5-3
direction :

5 CC GG 3

3 GG CC 5

Madam Im Adam
Racecar
Never odd or even
 PALINDOME

restrictase
EcoR1

STICKY ENDS
 Mitochondrial DNA
cicular ds DNA composed of unique sequences only, 2-10
copies/cell;
contians triple stranded regions (thy block replication
and transcription);
do not contain introns;
is not bound to histones;
autonomous replication and transcription;
specific genetic code some genes dont have
terminating codons;
maternal type of inheritance sperm mtDNA is
degraded, children from both genders inherit diseases;
low reparative ability, high mutation rate 10-100
higher;
mt DNA similar to prokaryotic DNA
appeared 107 years ago!
 Over 40 mitochondrial
diseases
Slow growth
Myopathies, tiredness
syndromes
Loss of muscular
coordination, muscular
feebleness
Difficulties in learning and
concentration
Mental reatardation
Demention
In adults diabetes type II,
diseases of Parkinson and
Alzheimer, brain stroke,
cancer
Drug-induced
mitochondrial injuries
Mitochondrial Eve
the most recent common
matrilineal ancestor from
whom all living humans are
descended
passed down from mother
to offspring, all mtDNA in
every living person is
directly descended from
hers
lived approximately
100,000200,000 years ago
 Functions of DNA
1. Coding (informational) :
- all cellular proteins
- histone proteins
- proteins in kinetochores and in mitotic spindle
2. Regulatory control of gene activity through
regulatory genes
3. Enzymatic deoxyribozymes with nuclease
activity
4. Binding to protiens, thus affecting gene
activity
5. Evolutionary through mutations; amplified
genes; mobile genetic elements
6. Behavioural nesting, breast feeding, bird
flights
 Ribonucleic acids (RNA)

Structure

P
Double Minor bases ribose
stranded
regions P

ribose U

ribose G

P
ribose C
Instability! P
 mRNA
Characteristics
1. highest Mw;
lowest quantity in the cell;
2. variety of different types;
short half-life;
long living mRNA in oocytes only;
DNA RNA Posttranscriptional
modification 3. stricktly regulated synthesis
5 tail depending on the requirements of
the cell;
3

4. form stable complex with ribosomes

during translation



 rRNA
1. Basic function-
structural !
2. Types:
prokaryotic - 5S, 16S
and 23S rRNA
eukaryotic - 5S, 5.8S,
18S, 28S rRNA
 rRNA
1. In eukaryotes is transcribed on amplified genes on definite
chromosomes (in humans chromosomes 13, 14, 15, 21,
22).
2. Has the highest content within the cell - 80% of the total
RNA content.
3. 23S rRNA has catalytic function in prokaryotes.
Catalytic function -
ribozymes

nucleolus
(nucleolus)
 tRNA
cloverleaf-like secondary structure
Structure
1. CCA 3 end binds the amino acid
2. Timidine loop binds the ribosome.
3. Variable loop binds regulatory
proteins.
4. Anticodon loop binds the codons
of mRNA
5. Dehydrouridine loop binds
aminoethylsynthetase.
 Characteristics of tRNA

1. basic functions transporter

and adaptor in translation;
3. 62 types of tRNA in
eukaryotic cells;
4. posttranscriptional
modification in a secondary
clover-leaf shape;
5. L-shaped 3D structure
(tertiary) that allows tRNA to fit
into the P and A sites of the
ribosome. P
 RNA
1. small nuclear RNA (snRNA) mainly in eukaryotes:
- high uracil content;
- in complex with small nuclear ribonuclear proteins (snRNP)
participate in the process of splicing in transcription.
2. heterogeneous nuclear RNA (hnRNA) precursor eukaryotic
RNA containing introns.
3. microRNA (miRNA) - small (22bp),functions in RNA
silencing and post-transcriptional regulation of gene expression.

FUNCTIONS of RNA
Translates genetic information from DNA into a protein
(mRNA).
Acts as transporter and adaptor in translation (tRNA).
Coding function in reverse transcription (in RNA-retroviruses).
Structural builds ribosomes (rRNA).
Catalytic function ribozymes (precursor rRNA which performs
autosplicing and produces mature RNA).