Week 7 Flashcards
What is the endomembrane system in eukaryotes composed of?
Nuclear membrane, endoplasmic reticulum (RE, SE), golgi and lysosomes
What is the SER? (smooth endoplasmic reticulum)
Most cell types have relatively little smooth ER (SER)
Phospholipid, fat and steroid (including sex hormones) manufacturer
Carbohydrate metabolism
In hepatocytes, breaks down stored glycogen to release glucose
Detoxifies lipid-soluble drugs such as barbiturates
(Adds charged water-soluble groups such as sulphate or glycuronic acid)
What is a specialised form of the SER? What does it do?
Sarcoplasmic Reticulum (Found in muscle cells)
- Network of tubular sacs
- Transmits electrical signals
- Sequesters calcium ions from the cytosol
- The level of intercellular calcium regulates muscle contraction in muscle cells.
What do muscles consist of?
Myofibrils, surrounded by sarcoplasmic reticulum.
What are myofibrils made up of?
Repetitive arrangement of filaments called sarcomere. (The region where myosin and actin filaments overlap)
In summary, How do muscle contractions occur?
Muscle cells receive action potentials from the neuromuscular junction through T tubules in the sarcoplasmic reticulum.
The sarcoplasmic reticulum releases calcium ions.
Calcium ions bind to troponin causing a conformational change in tropomyosin.
Myosin and actin can now interact which results in muscle contraction.
What is myosin vs actin?
Myosin = thick filaments
Actin = Thin filaments
Briefly What is the sliding-filament model
Actin and myosin slide over each other during muscle contraction, as a result of an influx of Ca ions.
H line - shortens during contraction, only myosin
A line - region containing length of a single myosin filament
I like - contains length of single actin
Z line - Sarcomere boundary and junction of actin and myosin filaments
What are the 4 classes of protein synthesis? Where does it begin?
Secreted, glycosylated, lysosomal enzymes, membrane bound proteins.
Begins in the cytosol
What proteins attach to the RER during protein synthesis?
Only ribosomes synthesising proteins with a specific signal peptide sequence.
The N-terminus of these proteins contains a signal peptide usually 20-30 amino acids long
What is glycosylation (in the RER)?
The addition of sugars or oligosaccharides
Glycosylation in the RER?
An oligosaccharide added in the RER. Composed of N-acetylglucosamine, mannose and glucose residues containing a total of 14 sugar residues transferred to the proteins in the RER
What is glycosylation (in the golgi)?
The principle modification, which occurs to the proteins as they pass through the golgi
Glycosylation of proteins in the golgi is essential, why?
Essential to their function,
for example in the case of mucin produced these are glycoproteins with long highly oligosaccharide chains which are essential to produce a highly hydrated gel like material
What are lysosomes?
Vesicular structures that contain hydrolytic enzymes.
When a lysosome fuses with a target, H+ pumped into secondary lysosome to bring down pH, activate enzymes
Carry out autophagy (recycling of organelles), phagocytosis, and apoptosis (cell-suicide)
Where do primary lysosomes originate?
The trans face of the golgi
What causes a lysosomal storage disease?
Partially degraded insoluble metabolites accumulate within lysosomes if a particular lysosomal enzymes is defective.
Resulting material results in enlarged lysosomes that compromise cell function in over 50 different lysosomal storage diseases.
Example of a lysosomal storage disease?
Tay-Sachs disease
Haxosaminidase A enzyme deficiency results in the accumulation of lipid ganglioside.
Symptoms due to accumulation of ganglioside in nerve cells. Death usually occurs by 2-3 years old
Briefly outline skeletal muscle contraction
Electrical impulse crosses sarcoplasmic reticulum, resulting in Ca released. They bind to troponin causing change in tropomyosin, which exposes the actin-myosin binding site so its available for myosin to bind to.
ATP hydrolysed into ADP and Pi, allowing for the myosin head to cock and change shape, causing the filaments to slide over one another. Causes a power stroke as the actin filament releases energy, therefore myosin head recocks to original shape causing muscle contraction
What is exocytosis?
Material exported out of a cell.
(important in the secretion of numerous proteins including hormones, and extracellular structural proteins such as collagen and fluids such as mucus. )
How does exocytosis occur?
Involves fusion of vesicles from the interior of the cell with the plasma membrane. The vesicles contents are then expelled into the surrounding medium.
What are the different types of endocytosis?
- Phagocytosis
- Pinocytosis
- Receptor-medicated endocytosis
Briefly what is phagocytosis?(endocytosis)
Uptake of insoluble material in protozoa, also a form of feeding
also occurs in macrophages as defence
Briefly outline pinocytosis (endocytosis)
Cells pinch their plasma membrane to take up extracellular fluid in small vesicles.
Non-specific.
Briefly What is receptor-mediated endocytosis?
Binding of macromolecules to specific cell surface receptors which triggers endocytosis.
How does SARS CoV-2 enter cells?
Via receptor-mediated endocytosis
Outline receptor-mediated endocytosis (the process)?
The macromolecules (such as transferrin which transports iron from the blood into cells) become concentrated in endocytic pits
The endocytic pits are coated with a bristle-like protein called clathrin
Clathrin polymerises around the vesicle forming a cage like structure
How does the signal recognition particle (SRP) stop and start protein translation in the RER?
A signal recognition particle (SRP) attaches to the signal peptide and stops translation in the cytosol.
The SRP docks to a SRP receptor on the ER membrane and translation starts again.
After the SRP restarts protein translation in the RER, what happens?
Hydrophobic signal peptide passes through the membrane and loops back through the membrane and is cleaved off. The rest of the peptide passes through the membrane and into the ER lumen
The signal sequence is cleaved off with the enzyme signal peptidase.
What are ribosomes (protein synthesis)?
Cell machinery for joining together amino acids which travel along the length of the mRNA during translation
What are polyribosomes (protein translation)?
An mRNA molecule is generally translated simultaneously by several ribosomes in clusters, these are known as polyribosomes
What is the role of the golgi in protein synthesis?
Proteins move from the RER to the golgi by small transport vesicles where they are modified and sorted.
It also mediates the flow of proteins from the RER to various destinations within the endomembrane system.
What is the default pathway after protein synthesis has occurred in the RER?
Through the golgi and then to the plasma membrane for secretion.
However some proteins are tagged in the golgi for specific destinations within the cell eg lysosomal enzymes
Give an example of where a protein doesn’t follow the typical pathway after being synthesised in the RER?
Mannose residues of lysosome enzyme proteins are phosphorylated in the cis golgi.
A mannose 6-phosphate receptor then binds these proteins in the trans golgi reticulum and directs their transfer to lysosomes
Who discovered autophagy?
Japanese biologist Yoshinori Ohsumi discovered the process by which a cell breaks down and recycles content.
He won the noble prize medicine award in 2016
Outline the signal mechanism for targeting proteins to the ER?
- mRNA leaves nucleus by nuclear pores,
- enters cytoplasm where ribosomes attach, synthesise peptide/protein
- If peptide has signal peptide, the peptide binds to a signal recognition particle (SRP) and this stops translation.
- mRNA and ribosome attached sent to translocation complex on surface of the endoplasmic reticulum and dock.
- Ribosome eventually detaches from the mRNA which releases the SRP into the cytosol ready for the next sequence.
- The rest of the synthesis for this protein occurs within the endoplasmic reticulum.
Give the typical pathway the protein that takes after being synthesised in the RER?
Produced in Rough ER, delivered to the cis golgi, comes out of trans golgi, packages into vesicles which take them for exocytosis and release the protein M6P out of the cell
What pathway does the protein take after being synthesised if it contains the mannose 6-phosphate (M6P)?
- Mannose residue attaches to the oligosaccharide during translation and the protein is phosphorylated.
- This is recognised by M6P receptor and is targeted as a lysosomal phosphorylated enzyme, therefore coated by clathrin.
- transported through the cytoplasm by a series of endosomes (specialised vesicles) where it ends up in the lysosome.
When is M6P receptor disassociated from the protein as it’s transported to the lysosome by endosomes?
A change in pH occurs during the transfer of the protein to endosomes where the M6P receptor disassociates from the protein so it can be recycled and used again.
Example of glycosylation in the golgi producing mucus?
Some proteins require a lot of sugar for example in the goblet cells that produce mucus, the glycoprotein musin is a sugar-heavy compound. Makes mucus have a unique viscous characteristic so it can complete its function: trapping cell debris and pathogens so ciliated cells can flush it away.
However, can cause the genetic disease Cystic Fibrosis if mucus is produced in too large amounts.
What is Histoclear?
A purified, stabilised product (C10H16, d-limonene) from oranges that is a safer alternative to xylene for clearing histological sections
What is the difference between a ciliated cell and a cell that has microvilli?
Ciliated cells are found in the respiratory tract and are single columnar epithelial cells with hair like projections which function to remove mucus. Microvilli are finger like projections that are found in the gastrointestinal tract and are on the surface of epithelial cells to increase surface area for absorption.
What is regular connective tissue and irregular connective tissue?
Dense irregular connective tissue generates a network mesh of fibers often found in joints and is impact resistant. Dense regular connective tissue is where the fibers are closely packed and arranged in a parallel fashion. This is often found in ligaments and tendons.
Loose connective tissue connect tissues together to form organs.
What is Endothelium?
Endothelium (endo - internal) include vessels. Epithelium (epi - outer) are boundary cells between the environment and our body including skin.
What is the endosymbiotic theory of mitochondrial origin?
Derive from a common ancestral organelle that originated from the integration of an endosymbiotic alphaproteobacterium into a host cell.
Transition entailed a massive number of evolutionary changes including origin of hundreds of new genes and a protein import system, insertion of membrane transporters, etc.
Evidence for endosymbiotic theory of mitochondrial origin?
- Double membrane
- Retain own genome
- Replicate somewhat independently
Where are mitochondria found within the cell?
Change their position inside the cell and are moved by microtubules of cytoskeleton
Often found in regions of high ATP consumption eg in myofibrils of muscle cells
What does the inner membrane of the mitochondria form?
Cristae
What are the two compartments in the mitochondria?
Matrix inside the inner membrane and the inter-membrane space between inner and outer membrane
What is the mitochondrion’s protein component?
Porin
(large aqueous channels)
What are the three major types of membrane complexes/processes in the mitochondria?
Electron transport chain
ATP synthase
Specific transporters of metabolites which vary according to cell/tissue type
Characteristics of the cristae (mitochondria)
increase membrane surface area
energy transducing membrane
impermeable to most small ions
What does the matrix of the mitochondria contain?
enzymes which catalyse Krebs cycle and fatty acid oxidation
ribosomes
mitochondrial DNA
Outline the process of mitochondrial respiration
During glycolysis, each glucose molecule is broken down into two molecules of the compound pyruvate. In eukaryotic cells, as shown here, the pyruvate enters the mitochondrion. There it is oxidized to acetyl CoA, which is further oxidized to CO2 in the citric acid cycle. NADH and a similar electron carrier, a coenzyme called FADH2, transfer electrons derived from glucose to electron transport chains, which are built into the inner mitochondrial membrane. During oxidative phosphorylation, electron transport chains convert the chemical energy to a form used for ATP synthesis in the process called chemiosmosis
Why is cyanide one of the most dangerous, fast acting poisons? (mitochondrial poisons)
Prevents passage of electrons from one of the cytochromes therefore blocking the electron transport chain.