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Functions of the molecules and organelles in the cell

Ueng-Cheng Yang

Sept. 13, 2005

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Cells: the basic unit of life

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Prokaryotic & eukaryotic cells

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Feeling of scales

Cell

Size

rangeMost Cells

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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

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Diffusion

• Concentration gradient

• It takes days to diffuse across a cell

• It can prevent colloidal particle from sedimenting (Tyndall effect).

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Organelles are functional units inside a cell

Cytoplasm cytosol organelles

Nucleus nucleolar nuclearplasm

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Sizes of cells and organelles

Bacteria 1 –5 m

Animal and Plant cells 10-50 m

Nucleus 5-6 m Mitochondria 2-3 m Chloroplasts 5-10 m

Nerve cells > 1 m

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Why is it necessary to have compartments?

• Increase efficiency, e.g. mitochondria

• Segregate molecules, e.g. lysosome

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Mitochondria

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Lysosome & peroxisome

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Compartments Are Formed by Lipids

• Membranes are phospholipids• Lipids are not soluble in water• Membranes can prevent molecules

from freely passing through the boundaries

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What Are Lipids?

• Triacyl glycerides

• Phospholipids

• Cholesterol

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Triacyl Glycerides

OR1 -C-O-CH2

OR2 -C-O-CH OR3 -C-O-CH2

fatty acid part glycerol part

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Ester and Phosphoester

R'-OH +

alcohol

OR-C OH

acid

OR-C O-R' H ester

R'-OH +

alcohol

OHO-P-OH OH

phosphoric acid

OHO-P-O-R' OH

phospho- ester

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Phospholipids Are Surfactants

O Lecithine CH3 -(CH2 )n - C-O-CH2 n ~ 16-20

O n' ~ 16-20 CH3 -(CH2 )n' -C-O-CH

O + CH3 Hydrophobic Tail CH2 -O-P-O-CH2 -CH2 -N-CH3

O- CH3

Hydrophilic Head

+

-+

-

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Surfactants Help to StabilizeThe Suspension

Soap removes oil Micelles

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Lipid Bilayer and Membrane

Hydrophobic Integral Peripheral tails protein protein Cholesterol

Hyrodphilic Polysaccharides head

HO

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How Can A Hydrophilic Molecule Pass through A Hydrophobic

Membrane?

Crossing the junction of two cells

Get into the cell from environment

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Endoplasmic reticulum (ER)

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Golgi apparatus

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Exocytosis And Endocytosis

exocytosis endocytosis

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Types of Endocytosis

• Phagocytosis ("cell eating solid particle")

• Pinocytosis ("cell drinking dissolved material")

• Receptor-mediated endocytosis ("cell taking up specific proteins")

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Receptor-Mediated Endocytosis And Capping

binding clustering capping

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Membrane Fluidity

Human + Mouse Fused

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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?

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Steady State

Input Output

Water levelappears constant

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What are the macroscopic differences of different

types of cells?

• Adipose tissue cells

• Capillary cells

• Muscle cells

• Nerve cells

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Cytoskeleton

microtubules: - tubulin - 25 nm (d)intermed. filaments: - vimentin or keratin - 10 nm (d)microfilament: - actin - 7 nm (d)

anti-actin anti-vimentin

anti-tubulin anti-keratin

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Orders in A Cell

• Compartments and localization

• Cytoskeleton and polarity

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The Importance of Polarity

It's easier to propagate asymmetry than to create asymmetry.

Cell division Budding yeast Frog oocyte

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The Origin of Polarity/ Asymmetry

WaterCHCl3

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The Second Law of Thermodynamics

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Orders Can Be Maintained by Energy Input

Water can flow upwards if ...

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How can a cell maintain all the structures?

Energy can compensate the entropy loss G = H - T S

=> Metabolism is a life phenomenon

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Discussion

Is phage or virus a life?

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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)

YM-Bioinfo

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What Is Life?

• Growth and development

• Metabolism

• Homeostasis

• Movement

• Response to stimuli

• Reproduction

• Evolution and adaptation

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Amino Acids Are the Structural Units of Proteins

NH2

H-C-COOH RAmino Acid

NH2

H-C-COO-

R (-)

NH3+

H-C-COOH R (+)

NH3+

H-C-COO-

R no charge

OH- OH-

(http://www.ym.edu.tw/bio/bch/aa.htm)

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Types of amino acids

• Charged– Positively charged: 3– Negatively charged: 2

• Hydrophilic, uncharged: 7

• Hydrophobic: 8Try to memorize it, so their properties become a “reflex” for you.

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Lysine (K) and arginine (R)

Basic amino acids

(positively charged at pH 7)

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Histidine (H)

Frequently used in general acid and base catalysis

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Aspartate (D) and glutamate (E)

Derived from intermediate metabolites

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OAA => Asp; -KG => Glu

OAA citrate

isocitrate

-ketoglutarate

succinyl CoAsuccinate

malate

fumarate

-2H-CO2

-2H-CO2

CoA

-2H

-2H

CoA + GTP

acetyl CoA

release CO2

reforming the carrier

H2O

TCA cycle

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What’s the difference among …

-ic acid: e.g. acetic acid

-tate: e.g. acetate

-yl: e.g. acetyl

OR-C-OH

OR-C-O-

OR-C-

For acetic acid derivatives, R=CH3

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Hydrophilic and uncharged

gly, cys, ser, thr, tyr, asn, gln

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glycine

The only amino acid that does not have stereochemistry

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alanine

Pyruvate => alaThis is a hydrophobic amino acid. It was discussed here for understanding the structur

e of Ser and Cys.

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serine and cysteine

Oxygen and sulfur are in the same column in periodic table

=> Should have similar properties

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Periodic table

* Picture made from screenshot of http://www.shef.ac.uk/~chem/web-elements/

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threonine and tyrosine

Ser, thr, and tyr have hydroxyl group, so they can be phosphorylated

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Phosphorylation cascade and signal amplification

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glutamine and asparagine

Gln helps to transport NH3 to kidney

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Amine and Amide

HR-N Hprimary amine

R'R-N Hsecondary amine

R'R-N R"tertiary amine

HR-N + H

amine

OR-C OH

acid

OR-C N-R H amide

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Hydrophobic amino acids

Ala + val, leu, ile, met, phe, trp, pro

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Valine (V), leucine (L), and isoleucine (I)

hydrophobic and branched

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Methionine (M)

S-adenosyl methionine is a methyl group donor in the cell

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Phenylalanine (F) and tryptophan (W)

A well known genetic disease: phenylketonuria

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Proline (P)

The only imino acid in 20 amino acids. It distort the normal peptide geometry.

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How to Use Mage?

Demonstration

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Schiff’s base

A way to form C-N bond

O OHR-C-H + H2N-R’ R-C-N-R’ R-C=N-R’ + H2O H

= --

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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