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Transcript
Biology
Lectures – winter term 2008
1st year of Pharmacy study
3rd Lecture
Chemical composition of living matter – chemical
basis of life. Atoms, molecules, organic
compounds – carbohydrates, lipids, proteins,
nucleic acids
Atoms
-protons,neutrons,electrons
electrons
electrons
Macroelements
H,O,C,N,P,S,Na,K,Cl,Fe,Mg
Microelements
I,Mn,F,Zn,Cu,Co,Se,.......
Bonds of atoms
Molecules
Bond – ionic, covalent, polar and non-polar
metán
Sodík
Chlór
NaCl
H2O
ATP
- energy
- Structure of
Nucleic acides
- signal molecule
Macromolecules
- sugars -saccharides
- lipids
- proteins
- nucleic acids
Sugars - saccharides
Monosaccharides
- pentose – ribose, deoxyribose
- hexose – glucose, fructose, galactose
Sugars - saccharides
disascharides
- saccharum, maltose, lactose
Sugars - saccharides
Polysaccharides
- starch, glycogen, cellulose
glucose
glucogen
Proteins
Proteins
Proteins
biogenic amino acids, names a codes
Aspartic Acid
Phenylanine
Alanine
Histidine
Lysine
Methionine
Proline
Arginine
Threonine
Tryptophan
Asp
Phe
Ala
His
Lys
Met
Pro
Arg
Thr
Trp
D
F
A
H
K
M
P
R
T
W
Glutamic Acid
Glycine
Cystine
Isoleucine
Leucine
Asparagine
Glutamine
Serine
Valine
Tyrosine
Glu
Gly
Cys
Ile
Leu
Asn
Gln
Ser
Val
Tyr
E
G
C
I
L
N
Q
S
V
Y
Amino acids
Amino acids sequence
3-D structure
Function of protein
Genetic
code
Proteins
Peptide bond
Proteins
Folding of proteins
Amino Acid Sequence
3-D Structure
Protein Function
α, β−Helix
pleadted sheet
3-D structure of proteins
1. Primary structure – amino acids sequence
(determine by mRNA)
2. secondary – α-or β-helix; pleated sheet
(H-bonds)
3. Tertiary – 3-D protein structure
(S-S bonds)
4. Quaternary – the final structure of proteins
(subunits, prostetic units and etc.)
3-D
Structure of
proteins
Three ways of proteins bonds
Proteins are hungry
Amino Acid Sequence
3-D Structure
Protein Function
Nucleic acids
DNA-RNA
Nucleic acids
DNA
Chromosome
Nucleus consists one or
more molecules DNA
organized into
chromosomes
Human:
– 22 pars autozomes
– 1 par sex
chromosome
Human karyotypes
Human and mouse chromosomes:
DNA chemical structure
Double helix of DNA
Double helix
• Two complementary DNA strains
• Spring will be 52th anniversary of its discovery
Detection of DNA
Detection of DNA
Red – increase of sample transcripts
Green – increase of sample transcripts
Yellow – equal abundance
Limit of Detection: 1 in 30,000 transcripts
~ 20 transcripts/cell
Affymetrix GeneChip®
Limits: 1: 100,000
transcripts
~ 5 transcripts/cell
Affymetrix GeneChip®
3-D Structure of DNA in nucleus
Nuclear membrane
Chromatin
fiber
Chromatin fiber
(30 nm dia.)
H1
Nucleosomes
H1
}
Nuclear
pore
Nuclear matrix
DNA
Other Chromatin
factors
DNA-protein complex
DNA
folding
Chromatin structure
Chromatin structure
DNA is wrapped around histone proteins as chromatin
The Obstacles are Regulated: Histone Modifications
A Histone Code?
Bromo
Domain
Chromo
Domain
• regulation of transcription
• complex of genes to the DNA locus
• protection of specific genes
All cells – the same DNA
- different reading of DNA
- differentiation of cells
Histones play
Key role in
Regulation of
gene expression
Transcription and
Processing
DNA in blue
PolyA+RNA in red
PolyA+RNA in red
(a spliceosomal component) in
green Overlap (red + green)
= yellow
RNA
• Ribonucleic
• Similar as DNA
• Tymine (T) is substituted by uracile (U)
• RNA can be:
– One-strain helix
– Double – strains helix
– Hybridisated with DNA
RNA
• RNA is usually one strain
• It forms the 3-D secondary and
tertiary structure
• The most important is extreme
variability of the RNA molecules sequence
tRNA: sequence, 3-D structure
mRNA
• Messenger RNA
• Linear molecule coded genetic
information – copy from DNA
• Transcription: process of copy mRNA
from DNA
mRNA modification
• Eukaryotic genes are built:
• Exons: coding regions
• Introns: non-coding regions
• splicing: cut of introns from molecule of mRNA
and link the exons
• After this modification of mRNA is translated to
sequence of protein
mRNA modification
Image source:
http://departments.oxy.edu/biology/Stillman/bi221/111300/processing_of_hnrnas.htm
tRNA
• Transfer RNA
• Precise 3-D structure
• The translation process of protein
tRNA structure
tRNA
• Specific tRNA for each amino acid
• Determine by 3 nucleotide - anticodone
(complementary with mRNA)
• Translation: process of prescription of
codons of mRNA to sequence of amino
acids to protein
tRNA
tRNA: sequence, 3-D structure
tRNA structure
rRNA
secondary
structure
16S ribosomal RNA
T. thermophilus - Ramakrishnan et al., Cell, 2002
Lipids
Schematic Diagram of a
phospholipid molecule
(phosphatidylcholine)
Phospholipids
• Membranes of mammalian cells
contain 3 major phospholipids
– Classified according to the polar
headgroup
Choline head-group
Polar
Phosphatidylcholine
Nonpolar
Saturated fatty acid
Unsaturated fatty acid
Differences in the
length and degree of
saturation of fatty
acids affect their
ability to pack
& hence the fluidity
of the bilayer
Amphipathic
A, formula
B, schematic drawing
C, space-filling model
Cholesterol is oriented in the membrane between phospholipid
molecules with its polar end towards the outside surface of the
monolayer and its hydrophobic end projecting into the interior of
the membrane
Lodish et al, Fig 5-30