Download The Chemistry of Life

Functions of the molecules and
organelles in the cell
Ueng-Cheng Yang
Sept. 13, 2005
TIGP/YMU
Cells: the basic unit of life
TIGP/YMU
Prokaryotic & eukaryotic cells
TIGP/YMU
Feeling of scales
Cell
Most
Cells
Size
range
TIGP/YMU
Why are cells small?
• Cells must exchange gases & other
molecules with environment…
• Nutrients in, Wastes out
• As size increases, the rate of diffusion
exchange slows down. For example,
hypoxia is observed when the diameter of
tumor is larger than 2 mm
• This is due to the ratio of surface area to
volume
TIGP/YMU
Diffusion
• Concentration gradient
• It takes days to diffuse across a cell
• It can prevent colloidal particle from
sedimenting (Tyndall effect).
TIGP/YMU
Organelles are functional units inside
a cell
Cytoplasm
cytosol
organelles
Nucleus
nucleolar
nuclearplasm
TIGP/YMU
Sizes of cells and organelles
Bacteria
1 –5 m
Animal and Plant cells
10-50 m
Nucleus
Mitochondria
Chloroplasts
5-6 m
2-3 m
5-10 m
Nerve cells
>1m
TIGP/YMU
Why is it necessary to have
compartments?
• Increase efficiency, e.g. mitochondria
• Segregate molecules, e.g. lysosome
TIGP/YMU
Mitochondria
TIGP/YMU
Lysosome &
peroxisome
TIGP/YMU
Compartments Are Formed
by Lipids
• Membranes are phospholipids
• Lipids are not soluble in water
• Membranes can prevent molecules
from freely passing through the
boundaries
TIGP/YMU
What Are Lipids?
• Triacyl glycerides
• Phospholipids
• Cholesterol
TIGP/YMU
Triacyl Glycerides
O
R1 -C-O-CH2
O
R2 -C-O-CH
O
R3 -C-O-CH2
fatty acid part glycerol part
TIGP/YMU
Ester and Phosphoester
O
R'-OH
+
R-C
R-C
OH
alcohol
R'-OH
alcohol
O
acid
O
+ HO-P-OH
OH
phosphoric
acid
O-R'
H
ester
O
HO-P-O-R'
OH
phosphoester
TIGP/YMU
Phospholipids Are Surfactants
O
CH3 -(CH2 )n - C-O-CH2
O
CH3 -(CH2 )n' -C-O-CH
Hydrophobic Tail
+
-
Lecithine
n ~ 16-20
n' ~ 16-20
O
+ CH3
CH2 -O-P-O-CH2 -CH2 -N-CH3
O
CH3
+
Hydrophilic Head
-
TIGP/YMU
Surfactants Help to Stabilize
The Suspension
Soap removes oil
Micelles
TIGP/YMU
Lipid Bilayer and Membrane
Hyrodphilic
head
Polysaccharides
Hydrophobic Integral Peripheral
tails
protein protein
HO
Cholesterol
TIGP/YMU
How Can A Hydrophilic Molecule
Pass through A Hydrophobic
Membrane?
Crossing the junction of two cells
Get into the cell from environment
TIGP/YMU
Endoplasmic reticulum (ER)
TIGP/YMU
Golgi apparatus
TIGP/YMU
Exocytosis And Endocytosis
exocytosis
endocytosis
TIGP/YMU
Types of Endocytosis
• Phagocytosis ("cell eating solid
particle")
• Pinocytosis ("cell drinking
dissolved material")
• Receptor-mediated endocytosis
("cell taking up specific proteins")
TIGP/YMU
Receptor-Mediated Endocytosis
And Capping
binding
clustering
capping
TIGP/YMU
Membrane Fluidity
Human
+
Mouse
Fused
TIGP/YMU
How to Maintain the Dynamic
Membranes?
• The final equilibrium of a suspension is
phase separation.
• Mechanical mixing or something else is
required for maintaining the micelles.
• Growing pains: How do you get new
material all the time?
TIGP/YMU
Steady State
Input
Output
Water level
appears constant
TIGP/YMU
What are the macroscopic
differences of different
types of cells?
•
•
•
•
Adipose tissue cells
Capillary cells
Muscle cells
Nerve cells
TIGP/YMU
Cytoskeleton
anti-actin
microtubules:
- tubulin
- 25 nm (d)
intermed. filaments:
- vimentin or
keratin
anti-tubulin
- 10 nm (d)
microfilament:
- actin
- 7 nm (d)
anti-vimentin
anti-keratin
TIGP/YMU
Orders in A Cell
• Compartments and localization
• Cytoskeleton and polarity
TIGP/YMU
The Importance of Polarity
It's easier to propagate
asymmetry than to
create asymmetry.
Cell division
Budding yeast
Frog oocyte
TIGP/YMU
The Origin of Polarity/
Asymmetry
Water
CHCl3
TIGP/YMU
The Second Law of
Thermodynamics
TIGP/YMU
Orders Can Be Maintained by
Energy Input
Water can flow upwards if ...
TIGP/YMU
How can a cell maintain all the
structures?
Energy can compensate the entropy loss
G= H-T S
=> Metabolism is a life phenomenon
TIGP/YMU
Discussion
Is phage or virus a life?
TIGP/YMU
Genome Structure of the SARS virus
(Marra et al., Rota et al., Ruan et al., 2003)
The RNA genome contains about 30k bps, having five major
open reading frames (ORFs):
ORF1a and ORF1b: replicase polyprotein (13149, 7887 bps)
S: spike glycoprotein
(3768 bps)
E: small envelope protein
(231 bps)
M: membrane glycoproteins
(666 bps)
N: nucleocapsid protein
(1269 bps)
and 7 unknown ORF’s X’s
(total 2595 bps)
TIGP/YMU
YM-Bioinfo
TIGP/YMU
YM-Bioinfo
What Is Life?
•
•
•
•
•
•
•
Growth and development
Metabolism
Homeostasis
Movement
Response to stimuli
Reproduction
Evolution and adaptation
TIGP/YMU
Amino Acids Are the Structural
Units of Proteins
NH2
H-C-COOH
R
Amino Acid
(http://www.ym.edu.tw/bio/bch/aa.htm)
NH3+
NH2
NH3+
OH
- OH
H-C-COOH
H-C-COO
H-C-COO
R
R
R
(+)
(-)
no charge
TIGP/YMU
Types of amino acids
• Charged
– Positively charged: 3
– Negatively charged: 2
• Hydrophilic,
uncharged: 7
• Hydrophobic: 8
Try to memorize it, so their properties become a “reflex” for you.
TIGP/YMU
Lysine (K) and arginine (R)
Basic amino acids
(positively charged at pH 7)
TIGP/YMU
Histidine (H)
Frequently used in general acid and
base catalysis
TIGP/YMU
Aspartate (D) and glutamate (E)
Derived from intermediate
metabolites
TIGP/YMU
OAA => Asp; a-KG => Glu
acetyl CoA
OAA
citrate
-2H
release CO2
isocitrate
TCA cycle
-2H
-CO2
H2O
reforming
a-ketoglutarate
fumarate the carrier
CoA
-2H
succinate succinyl CoA
-2H
-CO2
CoA + GTP
malate
TIGP/YMU
What’s the difference among …
O
R-C-OH
-ic acid: e.g. acetic acid
O
R-C-O-
-tate: e.g. acetate
O
R-C-
-yl: e.g. acetyl
For acetic acid derivatives, R=CH3
TIGP/YMU
Hydrophilic and uncharged
gly, cys, ser, thr, tyr, asn, gln
TIGP/YMU
glycine
The only amino acid that does not
have stereochemistry
TIGP/YMU
alanine
Pyruvate => ala
This is a hydrophobic amino acid. It was
discussed here for understanding the
structure of Ser and Cys.
TIGP/YMU
serine and cysteine
Oxygen and sulfur are in the same
column in periodic table
=> Should have similar properties
TIGP/YMU
Periodic table
* Picture made from screenshot of http://www.shef.ac.uk/~chem/web-elements/
TIGP/YMU
threonine and tyrosine
Ser, thr, and tyr have hydroxyl group,
so they can be phosphorylated
TIGP/YMU
Phosphorylation
cascade and
signal
amplification
TIGP/YMU
glutamine and asparagine
Gln helps to transport NH3 to kidney
TIGP/YMU
Amine and Amide
H
R'
R'
R-N
R-N
R-N
H
primary
amine
H
secondary
amine
R"
tertiary
amine
H
R-N
O
+
H
amine
R-C
O
R-C
OH
acid
N-R
H
amide
TIGP/YMU
Hydrophobic amino acids
Ala + val, leu, ile, met, phe, trp, pro
TIGP/YMU
Valine (V), leucine (L), and
isoleucine (I)
hydrophobic and branched
TIGP/YMU
Methionine (M)
S-adenosyl methionine is a methyl
group donor in the cell
TIGP/YMU
Phenylalanine (F) and tryptophan (W)
A well known genetic disease:
phenylketonuria
TIGP/YMU
Proline (P)
The only imino acid in 20 amino acids.
It distort the normal peptide geometry.
TIGP/YMU
How to Use Mage?
Demonstration
TIGP/YMU
Schiff’s base
A way to form C-N bond
-
-
=
O
OH
R-C-H + H2N-R’  R-C-N-R’  R-C=N-R’ + H2O
H
TIGP/YMU
Types of amino acids
• Charged
– Positively charged: Lys, Arg, His
– Negatively charged: Asp, Glu
• Hydrophilic: Gly, Ser, Cys, Thr,
Tyr, Asn, Gln
• Hydrophobic: Ala, Val, Leu, Ile,
Met, Pro, Phe, Trp
TIGP/YMU