Download Basic course, CDFD: Molecules of Life, 23-Aug-2007

Molecules of Life
Shekhar C. Mande
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Ecosystem
Rain forest, desert, fresh
water lake, digestive
tract of animal for
bacteria
Includes all living organisms and non living
matter such as air, water and minerals
Community
All species in an
ecosystem
Only includes living things from bacteria, to fungi,
to plant to animal
Population
All individuals of a single
species
Includes only individuals from a specific species
such as a plant, an animal, a bacterial colony
Organism
One single individual
Serves as a representative of the species and
describes overall form and function of an
organism
Organ
A specialized structural
system of an organism
The brain or the thymus of an animal
Tissue
A specialized
substructure of an organ
The nervous tissue and epithelial tissue are both
part of the brain
Cell
A single cell
A neuron, a skin cell, a root cell, bacteria, yeast,
paramecium
Molecule
A single large or small
molecule such as a
protein, DNA, sugar or
fatty acid
Molecules are the smallest part of biological
systems; they can be studied for their chemical,
physical properties, but are of particular interest
for their usefulness in biological systems.
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Composition of Cells
• C, H, N, O, S & P make up >99% of cellular weight
Percent of Total Cell
Weight
Number of Types of
Each Molecule
Water
70
1
Inorganic ions
1
20
Sugars & precursors
3
200
Amino acids & precursors
0.4
100
Nucleotides & precursors
0.4
200
2
50
0.2
~200
22
~5000
Lipids & precursors
Other small molecules
Macromolecules
(proteins,
acids & polysachharides)
nucleic
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Water distribution on the Earth
Total water
1,360,000,000 km³
Oceans
1,320,000,000 km³
97.2 %
Glaciers and ice
caps
25,000,000 km³
1.8 %
Ground water
13,000,000 km³
0.9 %
Fresh water in lakes, 250,000 km³
inland seas and
rivers
0.02 %
Water vapour
0.001 %
13,000 km³
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Basic properties of water:
+
Because of the unequal
distribution of charge,
water molecules attract
each other, and that is the
reason why they form
drops!
-
As water transpires off the leaves the
cohesion pulls more water up through
the vessels.
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Basic properties of water:
• It is the only natural substance which is found in all the
three states- gas, liquid and solid at the temperatures
normally found on the earth.
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Basic properties of water:
• Anomalous properties enormously important in
maintaining the ecosystem of the Earth.
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Basic properties of water:
• It has very high surface tension- also the molecular basis of capillary action=
allows through roots of plants, and tiny blood vessles
T = surface tension (J/m² or N/m)
θ = contact angle
ρ = density of liquid (kg/m3)
g = acceleration due to gravity (m/s²)
r = radius of tube (m)
For a 1m wide tube, the water would
rise a unnoticable 0.014mm. However,
for a 1cm wide tube, the water would
rise 1.4mm, and for a capillary tube with
radius 0.1mm, the water would rise
14cm, or around 6 inches.
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Basic properties of water:
Water has high heat of vaporization: the amount of heat needed to turn
a given amount of liquid water into water vapour (gas).
A high heat vaporization means that in order for
water to reach the gaseous state, it must absorb a
great deal of heat from the surroundings. For many
plants and animals, this property is the basis of a
natural cooling system. Water evaporating from
leaves, skin or lungs uses up heat from the
organisms in the process of changing from liquid to
gas. That is the reason mammals have evolved
sweat glands, when the body is overheated, the
glands pour watery "sweat" onto the skin, as the
water evaporated, large amounts of body heat are
used up and the body is cooled.
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Basic properties of water:
• Has high specific heat index= it can absorb lot of heat before it
starts getting hot.
Due to it high specific heat, water is slow to undergo changes
in temperature. Much heat must be added or removed before
the temperature of water changes much. The temperature of
the water within living organisms tends to change more slowly
than does that of the surrounding air or soil, so that the living
cells are buffered somewhat against temperature fluctuations.
This kind of protection is important because many
biochemical reactions will take place only within a narrow
range of temperatures.
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Miller Urey Experiment
• 1953, starting material CH3, NH3, H2 and H2O
• Compounds observed included nucleotide bases
and amino acids
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Biomolecular Building Blocks
• Combinations of four types methyl (-CH3), hydroxyl (OH), carboxyl (-COOH) and amino (-NH3)
• Four different types of molecular building blocks:
Sugars
Amino acids
Fatty acids
Nucleotides
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Sugars
Glucose
They are important
metabolically. Sugars are the
major energy storage
molecules for living organisms.
Their carbon rings contain
Fructose
large amounts of energy
C6H12O6
6CO2 + 6H2O
releases 686 Kcal/mol
Deoxyribose
Ribose
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Cell Membrane
Protects cellular components from
diffusing into external environment
Membrane components may:
•be protective
•regulate transport in and out of cell or subcellular domain
•allow selective receptivity and signal transduction by providing transmembrane
receptors that bind signaling molecules
•allow cell recognition
•provide anchoring sites for cytoskeletal filaments or components of the extracellular
matrix. This allows the cell to maintain its shape and perhaps move to distant sites.
•help compartmentalize subcellular domains or microdomains
•provide a stable site for the binding and catalysis of enzymes.
•regulate the fusion of the membrane with other membranes in the cell via specialized
junctions )
•provide a passageway across the membrane for certain molecules, such as in gap
junctions.
•allow directed cell or organelle motility
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Membrane lipids
Choline
Phosphate
Glycerol
Fatty acid
•Phospholipids are the principal lipids in cell membranes
•They contain polar head group and hydrophobic tail
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Nucleotides
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Bases
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Amino Acids
Genetic code specifies 20 different amino acids
CH3
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Chirality of Amino Acids
R
R
C
C
H
H
N
CO
L- form
CO
N
D- form
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Protein Structures
• Primary structure
– Un-branched polymer
– 20 side chains (residues or amino acids)
• Higher order structures
– Secondary: local (consecutive) in sequence
– Tertiary: 3D fold of one polypeptide chain
– Quaternary: Chains packing together
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Primary Structure
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Protein Architecture
• Proteins consist of amino acids linked by
peptide bonds
• Each amino acid consists of:
– a central carbon atom
– an amino group
– a carboxyl group and
– a side chain
• Differences in side chains distinguish the
various amino acids
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Amino Acids and Their Symbols
Residue
Alanine
Glutamate
Three- letter
symbol
Ala
Glu
One-letter
symbol
A
E
Glutamine
Aspartate
Asparagine
Leucine
Glycine
Lysine
Serine
Valine
Arginine
Threonine
Proline
Isoleucine
Methionine
Phenylalanine
Tyrosine
Cysteine
Tryptophan
Histidine
Gln
Asp
Asn
Leu
Gly
Lys
Serine
Valine
Arg
Thr
Pro
Ile
Met
Phe
Tyr
Cys
Trp
His
Q
D
N
L
G
K
S
V
R
T
P
I
M
F
Y
C
W
H
Mnemonic
Alanine
GluEtamic
acid
Q-tamine
AsparDic acid
AsparagiNe
Leucine
Glycine
Before L
Serine
Valine
aRginine
Threonine
Proline
Isoleucine
Methionine
Fenylalanine
tYrosine
Cysteine
tWo rings
Histidine
pKa
4.3
3.9
10.5
12.5
10.1
6.0
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of 20 amino acids
• Hydrophobic
– Ala, Val, Leu, Ile, Phe, Pro, Met
• Charged
– Arg, Asp, Glu, Lys
• Polar
– Ser, Thr, Tyr, Asn, Gln, His, Cys, Trp
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Convention of Naming Side Chain Atoms
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Polypeptide Chain
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of Amino Acids
•Glycine increases main chain flexibility.
•Symmetry at the C atom
•Can adopt many different conformations
•Evolutionarily conserved
•Occurs in tight turns
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of Amino Acids
•Alanine is smallish non-polar residue
•Occurs abundantly
•No preference for inside or surface of the protein
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of Amino Acids
•Val, Leu and Ile are branched side chains
•Branching allows limited internal flexibility
•Occur primarily in protein cores
•“Bricks” around which functional parts are assembled
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of Amino Acids
•Phe, Tyr and Trp are the aromatic side chains
•All these contain one methylene group as a spacer
•Side chain flexibility is restricted
•Occur predominantly in the core of proteins
•Tyr can form strong H-bond with its -OH group
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of Amino Acids
•Met and Cys are the sulfur containing side chains
•Met is rather large and flexible
•Met occurs predominantly inside the core
•Cys is special: it can form disulfide crosslinks and is
polar
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of Amino Acids
•Asn and Gln have amide in side chain
•Gln has an extra methylene group, rendering the polar
group flexible and reducing its interaction with main
chain
•H- bond donor as well as acceptor
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of Amino Acids
•Asp and Glu are -vely charged at physiological pH
•Althoughly chemically similar, markedly different effect on the conformation
and chemical reactivity
•Asp relatively rigid, and found frequently in active sites
•Mostly found on protein surfaces
•Can be effective chelators of metal ions
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of Amino Acids
•Lys and Arg are +vely charged residues
•Long and flexible
•Can form salt bridges or help in catalysis
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of Amino Acids
•Ser and Thr are small and aliphatic
•-OH no more reactive than ethanol
•Frequently form H-bond with main chain
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of Amino Acids
•Pro is imino acid
•Reduces main chain flexibility drastically due to
cyclization
•Can often occur in cis- form
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Properties of Amino Acids
•His is a very special residue with pKa of 6.0
•Can be uncharged or charged easily
•Very suitable for catalysis, found in most active
centres
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Chemical Similarity Reflects in
Substitution Matrices
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Hydrophobicities
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Comparison of Kyte-Doolittle,
Eisenberg and White Scales
NAME
EIS
KD
WHI
ALA
0.62 1.80 -0.50
ARG
-2.53 -4.50 -1.81
ASN
-0.78 -3.50 -0.85
ASP
-0.90 -3.50 -3.64
CYS
0.29 2.50 0.02
GLN
-0.85 -3.50 -0.77
GLU
-0.74 -3.50 -3.63
GLY
0.48 -0.40 -1.15
HIS
-0.40 -3.20 -2.33
ILE
1.38 4.50 1.12
LEU
1.06 3.80 1.25
LYS
-1.50 -3.90 -2.80
MET
0.64 1.90 0.67
PHE
1.19 2.80 1.71
PRO
0.12 -1.60 -0.14
SER
-0.18 -0.80 -0.46
THR
-0.05 -0.70 -0.25
TRP
0.81 -0.90 2.09
TYR
0.26 -1.30 0.71
VAL
1.08 4.20 0.46
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Peptide torsion angles
Basic course, CDFD: Molecules of Life, 23-Aug-2007
Some mostly beta architectures
Basic course, CDFD: Molecules of Life, 23-Aug-2007
The Protein Folding Problem
Basic course, CDFD: Molecules of Life, 23-Aug-2007