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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