1Biochemistry

Biolog. Nanostructures

Chemistry of biological Nanostructures:

Chemistry of biological Nanostructures:

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Books: Berg et al., 6th ed., Biochemistry, Freeman & Co

Lodish et al, 6th ed., Molecular Cell Biology, Freeman&Co

1st Lecture:IntroductionThe compartments (organelles) in the cell: Function and how they look (structures) (Lodish 9.1, 10.1, 10.2)Biological membrane (Berg 12.1, 12.2, 12.3, 12.5)

2nd Lecture:Enzymes: Basic Concepts + Kinetic (Berg 8)

3rd Lecture:Exploring Proteins (Berg 3)

4th Lecture:Glycolysis (Berg 16)

5th Lecture:The Citric Acid Cycle (Berg 17)

6th Lecture:Oxidative Phosphorylation (Berg 18)

7th Lecture:Fatty Acid Metabolism (Berg 22)

8th Lecture:Biosynthesis of Membrane Lipids and Steroids (Berg 26)

9th Lecture:Amino Acid Metabolism (Berg 23 + 24)

10th Lecture:Integration of Metabolism (Berg 27)

Biochemistry:

Chemistry of biological Nanostructures:

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Books: Berg et al., 6th ed., Biochemistry, Freeman & Co

Lodish et al, 6th ed., Molecular Cell Biology, Freeman&Co

11th Lecture:Protein Trafficking (Lodish 13.1, 13.2, 13.3 +14.1, 14.2, 14.3, 14.4, 14.5 and Berg 30.6)

12th Lecture:Cytoskeleton (actin, microtubes) (Lodish 17 + 18, not 18.6 ) + Molecular Motors (Berg 34.4)

13th Lecture:Membrane channels and pumps (Berg 13)

14th Lecture:Signal Transduction (Berg 14)

15th Lecture:Photosynthesis (Berg 19)

Biological Nanostructures:

Cells• Basic building blocks of life

• Smallest living unit of an organism

• Grow, reproduce, use energy, adapt, respond to their environment

• Many cannot be seen with the naked eye

• A cell may be an entire organism or it may be one of billions of cells that make up the organism

• Basis Types of Cells

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-> Nucleoid region contains the DNA-> Cell membrane & cell wall-> Cytoplasm Contains ribosomes (no membrane)

-> Nucleus-> Cell Membrane (maybe cell wall)-> Cytoplasm with organelles

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Prokaryotic Cell

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Cytoplasm of Prokaryotic Cells:-> dense gelatinous solution of sugars, amino acids, and

salts

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Cell Envelope of Prokaryotic Cells

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Animal cell

Plant cell

1 Plasma membrane

2 Mitochondria

3 Lysosomes

4 Nuclear envelope

5 Nucleus

6 Chromatin

7 Smooth Endoplasmic Reticulum

8 Rough Endoplasmic Reticulum

9 Golgi

10 Secretory vesicles

11 Peroxisomes

12 Cytoskeletal fibers

13 Microvilli

14 plant cell wall

15 Plant Vacuoles

16 Plant Chloroplasts

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Characteristic Bio-membranes and Organelles

Plasma MembraneA lipid/protein/carbohydrate complex, providing a barrier and containing transport and signaling systems. NucleusDouble membrane surrounding the chromosomes and the nucleolus. Pores allow specific communication with the cytoplasm. The nucleolus is a site for synthesis of RNA making up the ribosome

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Nucleus:

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Duploid set of human chromosomes: 46-> 2 x 22 + (XY)

-> genomic DNA (chromatin)-> nucleus metabolic active (Transcription, Replication, rRNA, tRNA)

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Chromatin structure of Chromosomes

Histone proteins

Characteristic Bio-membranes and Organelles

MitochondrionSurrounded by a double membrane with a series of foldscalled cristae. Functions in energy production through metabolism. Contains its own DNA, and is believed to have originated as a captured bacterium.

Plasma MembraneA lipid/protein/carbohydrate complex, providing a barrier and containing transport and signaling systems. NucleusDouble membrane surrounding the chromosomes and the nucleolus. Pores allow specific communication with the cytoplasm. The nucleolus is a site for synthesis of RNA making up the ribosome

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Mitochondria

-> Energy factory !!

Most ATP production of nonphotosynthetic, aerobic cells

-> have DNA (protein production)

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Characteristic Bio-membranes and Organelles

MitochondrionSurrounded by a double membrane with a series of foldscalled cristae. Functions in energy production through metabolism. Contains its own DNA, and is believed to have originated as a captured bacterium.

Plasma MembraneA lipid/protein/carbohydrate complex, providing a barrier and containing transport and signaling systems. NucleusDouble membrane surrounding the chromosomes and the nucleolus. Pores allow specific communication with the cytoplasm. The nucleolus is a site for synthesis of RNA making up the ribosome

Chloroplasts (plastids)Surrounded by a double membrane, containing stacked thylakoid membranes. Responsible for photosynthesis, the trapping of light energy for the synthesis of sugars. Contains DNA, and like mitochondria is believed to have originated as a captured bacterium.

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Chloroplast

-> in plants and algae

-> Photosynthesis (ATP synthesis) takes place in the Thylakoid membranes (Chlorophyll )

-> have DNA (protein production)

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Rough endoplasmic reticulum (RER)A network of interconnected membranes forming channels within the cell. Covered with ribosomes (causing the "rough" appearance) which are in the process of synthesizing proteins for secretion or localization in membranes.RibosomesProtein and RNA complex responsible for protein synthesis

Smooth endoplasmic reticulum (SER)A network of interconnected membranes forming channels within the cell. A site for synthesis and metabolism of lipids. Also contains enzymes for detoxifying chemicals including drugs and pesticides.

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Endoplasmatic Reticulum:

Smooth ER: -> lacks ribosomes, synthesis of FA and phospholipids in liver: detoxification of pesticides and cancerogens

Rough ER: -> covered with ribosomes synthesis of membrane proteins and secreted proteins secretion -> vesicles carry proteins to golgi

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Rough endoplasmic reticulum (RER)A network of interconnected membranes forming channels within the cell. Covered with ribosomes (causing the "rough" appearance) which are in the process of synthesizing proteins for secretion or localization in membranes.RibosomesProtein and RNA complex responsible for protein synthesis

Smooth endoplasmic reticulum (SER)A network of interconnected membranes forming channels within the cell. A site for synthesis and metabolism of lipids. Also contains enzymes for detoxifying chemicals including drugs and pesticides.

Golgi apparatusA series of stacked membranes. Vesicles (small membrane surrounded bags) carry materials from the RER to the Golgi apparatus. Vesicles move between the stacks while the proteins are "processed" to a mature form. Vesicles then carry newly formed membrane and secreted proteins to their final destinations including secretion or membrane localization.

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Golgi:

-> processes membrane and secreted proteins (glycosylation)

-> protein sorting (membrane + secreted + transport to different organelles)cis-Golgi, medial-Golgi, trans-Golgi

Secretory pathway:Vesicles transporting proteins from the endoplasmic reticulum fuse with the cis-Golgi and subsequently progress through the stack to the trans-Golgi via vesicles.

Cell features for secretion of large amount of proteins:

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Secretary pathway:

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Rough endoplasmic reticulum (RER)A network of interconnected membranes forming channels within the cell. Covered with ribosomes (causing the "rough" appearance) which are in the process of synthesizing proteins for secretion or localization in membranes.RibosomesProtein and RNA complex responsible for protein synthesis

Smooth endoplasmic reticulum (SER)A network of interconnected membranes forming channels within the cell. A site for synthesis and metabolism of lipids. Also contains enzymes for detoxifying chemicals including drugs and pesticides.

Golgi apparatusA series of stacked membranes. Vesicles (small membrane surrounded bags) carry materials from the RER to the Golgi apparatus. Vesicles move between the stacks while the proteins are "processed" to a mature form. Vesicles then carry newly formed membrane and secreted proteins to their final destinations including secretion or membrane localization. Lysosymes

A membrane bound organelle that is responsible for degrading proteins and membranes in the cell, and also helps degrade materials ingested by the cell. 23

Structures that participate in delivering material to lysosomes:

Endocytosis is a process whereby cells absorb material (molecules or other cells) from outside by engulfing it with their cell membranes. It is used by cells because most substances important to them are polar and consist of big molecules, and thus cannot pass through the highly hydrophobic plasma membrane. Endocytosis is the opposite of exocytosis, and always involves the formation of a vesicle from part of the cell membrane.Phagocytosis (literally, cell-eating) is the process by which cells ingest large objects, such as prey cells or large chunks of dead organic matter. The membrane folds around the material, and vesicles are sealed off into large vacuoles. Lysosomes then merge with the vacuoles, turning them into a digestive chamber. The products of the digestion are then released into the cytosol. Macrophages are cells of the immune system that specialize in the destruction of antigens (bacteria, viruses and other foreign particles) by phagocytosis. Autophagy, or autophagocytosis, is a process of organelle degradation that takes place inside the cell. It is executed by lysosomes and is part of everyday normal cell growth and development. Its main purpose is to maintain a balance between biogenesis (production) of cell structures, and their degradation and turnover. For example, a liver-cell mitochondrion lasts around ten days before it is degraded and its contents are reused. 24

Lysosomes: -> trash bin of the cell !!!

-> acid organelle, contains degrading enzymesEnzymes: nuceases, hydrolases, proteases, phosphatasesInvolved in uptake of material (endocytosis, phagocytosis) and degradation of organelles (autophagocytosis)

Tay-Sachs disease: defect enzyme to break down gangliosides -> accumulation of glycolipids

VacuolesMembrane surrounded "bags" that contain water and storage materials in plants.

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Plant Vacuole:

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-> storage of small molecules (water, ions, sucrose, amino acids)

-> up to 80 % of plant cell

VacuolesMembrane surrounded "bags" that contain water and storage materials in plants.

Peroxisomes or MicrobodiesProduce and degrade hydrogen peroxide, a toxic compound that can be produced during metabolism.

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Peroxisomes:

-> contain oxidative enzymes, such as D-amino acid oxidase, ureate oxidase, and catalase.

-> resemble a lysosome

-> self replicating, like the mitochondria.

-> function to get rid of toxic substances like hydrogen peroxide, or other metabolites. They are a major site of oxygen utilization and are numerous in the liver where toxic byproducts are going to accumulate.

Diameter: 0.2 – 1 µm

VacuolesMembrane surrounded "bags" that contain water and storage materials in plants.

Peroxisomes or MicrobodiesProduce and degrade hydrogen peroxide, a toxic compound that can be produced during metabolism.

Cell wallPlants have a rigid cell wall in addition to their cell membranes

Cytoplasmenclosed by the plasma membrane, liquid portion called cytosol and it houses the membranous organelles.

CytoskeletonArrays of protein filaments in the cytosol. Gives the cell its shape and provides basis for movement. E.g. microtubules and microfilaments.

http://www.biology.arizona.edu copyright © 1997 - 2004.. 29

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Biological Lipids form Bilayer Structures (self assembly) -> Vesicle-like Structures

Membranes are a natural barrier

Biological Membrane

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All Organelles are protected by membranes (single or double)

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Major Membrane Lipids

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The Fluid Mosaic Model:

1. Membranes are 2-dimentional solutions of oriented lipids and proteins2. Membrane proteins can diffuse laterial in lipid matrix -> lipid is solvent

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Membrane Fluidity is controlled by fatty acid composition

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Membrane Composition determines Shape of Membrane

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Biological Membrane

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Membrane Proteins:

α-helical protein

β-barrel protein

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Membrane Anchor Proteins

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Membrane attached protein can be part of receptors

Receptors can be involved in Intracellular signaling -> Signal Transduction

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Signal from outside the cell (organel) -> induces signal inside

Photosynthesis

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Light drives a proton pump -> generation of energy (ATP)

Cell mobility (Molecular Motors)

Bacteria: Flagella Higher Eukaryotes: change in cell shape

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Molecular Organisation of a cell

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Many Important Biomolecules are Polymers

• Biopolymers - macromolecules created by joining many smaller organic molecules (monomers)

• Condensation reactions join monomers (H2O is removed in the process)

• Residue - each monomer in a chain

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Biomolecules – Structure

• Building block• Simple sugar• Amino acid• Nucleotide• Fatty acid

• Macromolecule• Polysaccharide• Protein (peptide)• RNA or DNA• Lipid

Anabolic

Catabolic

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Linking MonomersCells link monomers by a

process called dehydration synthesis (removing a

molecule of water)

This process joins two sugar monomers to make a double

sugar

Remove H

Remove OH

H2O Forms

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Breaking Down Polymers• Cells break down

macromolecules by a process called hydrolysis (adding a molecule of water)

Water added to split a double sugar

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Concepts of Life

Life is characterized by

• Biological diversity: lichen, microbes, jellyfish, sequoias, hummingbirds, manta

rays, gila monsters, & you

• Chemical unity: living systems (on earth) obey the rules of physical and organic chemistry – there are no new principles

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Life needs 3 things:

(1) ENERGY, which it must know how to:

• Extract• Transform• Utilize

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The Energetics of Life

•Photosynthetic organisms capture sunlight energy and use it to synthesize organic compounds

•Organic compounds provide energy for all organisms

Using toxic O2 to generate energy

2 H2O O2 + 4e- + 4H+ (photosynthesis)

Glucose + 6O2 6CO2 + 6H2O + Energy

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Glycolysis: the preferred way for the formation of ATP

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Life needs (2) SIMPLE MOLECULES, which it must know how to:

• Convert• Polymerize• Degrade

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Life needs (3) CHEMICAL MECHANISMS, to:

• Harness energy• Drive sequential chemical reactions• Synthesize & degrade macromolecules• Maintain a dynamic steady state• Self-assemble complex structures• Replicate accurately & efficiently• Maintain biochemical “order” vs outside

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Trick #1: Life uses chemical coupling to drive otherwise unfavorable reactions

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Trick #2: Life uses enzymes to speed up otherwise slow reactions

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How does an enzyme do it, thermodynamically?

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Summary of Key Concepts

Even though thousands of pathways sound very large and complex in a tiny cell:

• The types of pathways are small

• Mechanisms of biochemical pathways are simple

• Reactions of central importance (for energy production & synthesis and degradation of major cell components) are relatively few in number

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