topic 9 - cells Flashcards
what does a cell look like?
Typical cell:
65% Water
20% Protein
12% Lipids
1.5% Inorganics
1.0% RNA
0.4% Other organics
0.1% DNA
cell membrane, cytoplasm, mitochondrion, nucleus, DNA, endoplasmatic reticulum, lysosome, ribosome and golgi apparatus.
what comprises the Cell Membrane?
Composition: Various lipids (50% by mass), mainly phospholipids, proteins and sugars (glycans)
Provides a boundary between living cell and external world
Hydrophobic layer prevents polar and large molecules passing
Moderately non-polar molecules can pass through
Highly hydrophobic molecules will enter and not leave
Getting through membranes is a major consideration of drug development
Can branch out and bud off to create vesicles or form folds to engulf particles.
Lipid bilayer at drug target: inhalable anaesthetics are thought to change neuron membrane permeability and hence signalling.
Breaking the barrier can be done by adding molecules which tunnel and disrupt the membrane
Or by adding specific carriers which will bring another molecule across the membrane.
There are also many membrane proteins which are drug targets.
what comprises the Nucleus?
Composition: DNA (3 bn base pairs), proteins (histones, transcription factors, organisation), lipid membrane
The nucleus is where genetic information is stored and used as DNA
Each long strand of DNA (chromosome) is coiled around histone proteins
Further proteins compact and organise the DNA
Chromosomes are loosely folded except in cell division
The chromosomes each occupy their own space.
Glycerophosophlipids, sphingolipids. Some phosphorylated.
Pores allow proteins in, and mRNA and ribosomes out.
Transcription of DNA into RNA occurs in the nucleus
Genes are expression is controlled by transcription factors – proteins which bind DNA and initiate transcription
Drug targets include:
DNA (e.g. cis-platin, doxorubicin) transcription factors – usually for killing cancer cells
what comprises the Nucleous?
Densest area of the nucleus.
Site of ribosome production.
Requires RNA transcription and association with proteins
Composition: proteins, DNA, RNA
Camptothecin – disrupts topoisomerase in nucleolus to stop ribosome production in cancer.
what comprises the Cytoplasm?
Composition: water (~70%), ions, small molecules, proteins (up to 30%)
More viscous than water – but not more than 1.5x.
Molecules move slowly due to collisions
Where most metabolism (processing of small molecules) happens
Medium for signal transduction.
what comprises the Mitochondria?
Composition: Lipids, proteins, DNA, RNA, small molecules
Production of adenosine triphosphate (ATP) by ATP synthase which sits on the inner membrane (see metabolism lecture)
ATP is standard ‘fuel’ for proteins
Heat production
Mitochondria have their own DNA, transcription, translation machinery
Dysfunction contributes to neurodegeneration, metabolic disease (e.g. diabetes) , heart failure, and infections.
IMEGLIMIN
Against diabetes:
Blocks oxidative phosphorylation
Increases muscle glucose uptake.
What comprises the Endoplasmic Reticulum?
Composition: Lipids (phospholipids), proteins, RNA.
Continuous with nuclear membrane
An intracellular transport system
Forms network of membranes
‘Rough’ ER is studded with ribosomes
These produce proteins which will be exported outside the cell
‘Smooth’ ER lack these and is more involved in lipid biosynthesis - enzymes.
Lovastatin
Reduces cholesterol biosynthesis
Inhibits the enzyme HMG-CoA reductase, found in ER membranes.
what comprises the Golgi aparatus?
Composition: Lipids (phospholipids),
proteins
Receives proteins from ER in vesicles
Applies post-translational modifications to proteins
Phosphorylation
Glycosylation
Sulfation.
Transports them to internal or external vesicles.
what comprises the ribosomes?
Composition: RNA and protein.
Produce proteins by translating mRNA into polypeptides via tRNAs
Found in cytoplasm, mitochondria and rough ER.
Streptomycin
- antibiotic
- Blocks joining together of the two subunits of bacterial ribosome.
what comprises Endosomes and Lysosomes?
Composition: lipid membrane, contents
- Endosomes are lipid-bilayer bounded compartments within the cell
- They bud off from the ER and Golgi to transport or excrete proteins etc.
- They bud off from the cell membrane to allow the cell to uptake material from without (endocytosis)
- Endosomes can evolve into lysosomes which are acidic and break down their contents
- Lysosomal escape is critical for nucleic acid therapeutics and other nanoparticle therapies since large molecules cannot diffuse through the membrane
what comprises the Cytoskeleton?
Composition: Proteins
Helps cell keep shape, move, divide
Microtubules
polymers of tubulin proteins
25 nm wide, ~5 μm long
Hollow
Transport of organelles
Division of chromosomes
Microfilaments
Polymers of actin proteins
7 nm wide, double helix
Cell motility, contraction
Muscle movement.
Paclitaxel
- Anticancer drug
- Targets tubulin, inhibits cell division
what are the types of cell?
Different cell types for different jobs
Each cell will express a different range of proteins
Different cell surface properties
Different levels of uptake
Different locations in the body
= vital to get drug to correct cell type
types of cell:
sex cell
muscle cell
fat cell
bone cell
blood cell
nervous cell
epithelial cell
immune cell
stem cell.
other organisms
animal cell - centrioles (centrosome), cell membrane, vacuole, ribosomes, endoplasmic reticulum, mitochondrion, nucleus, nucleolus, chromosomes, golgi complex, cytoplasm.
plant cell - plasma membrane, vacuole, chloroplast, ribosomes, cell wall, plasmodesma, cytoplasm, golgi complex, chromosomes, nucleolus, nucleus, mitochondrion, endoplasmic reticulum.
bacteria cell (bacillus type) - chromosome, ribosomes, flagella, mesome, pill, capsule, plasma membrane, cell wall.
(Fungal cells are similar to animal cells, but with cell walls)
summary of Cells
Cells are the building blocks of organisms
They are separated from non-living matter and compartmentalised by lipid membranes
In human cells:
The nucleus contains the genetic information and is the site of transcription and replication
The cytoplasm is the site of many reactions and signal transductions
The mitochondria perform many metabolic tasks and provide ATP
The ER and Golgi are involved in trafficking of proteins and lipids
Transport also occurs through vesicles, endosomes, and lysosomes, and along the cytoskeleton
There are many different types of cells…
Dysfunction in one type of cell, or one organelle, or one protein provides a route to development of drugs.
