PRIN401 WEEK 4
Organization of the cell
Organization of the cell
Mycobacterium tuberculosis bacteria are able to survive in the host because:
they are adapted to survive and replicate inside phagocytic vesicles and lysosomes.
After the bacteria are phagocytosed by macrophages, the bacteria prevent phagosome-lysosome fusion and multiply in the phagosome until the macrophage bursts
Which of the following does not occur in mitochondria?
DNA replication
Glycolysis
Oxidative phosphorylation
Pyruvate decarboxylation
Tricarboxylic acid (TCA) cycle
a) Mitochondrial DNA is replicated in mitochondria.
*b) Glycolysis occurs in the cytoplasm.
Which of these molecular species is involved in targeting a secretory vesicle to the plasma membrane?
serum protein that is improperly folded during synthesis in the hepatocyte would normally be:
I. retained in the endoplasmic reticulum
II. retained in the Golgi apparatus
III. secreted then endocytosed and degraded in the lysosome
IV. transported to the cytoplasm and degraded in the lysosome
V. transported to the cytoplasm and degraded in the proteasome
Lysosomal enzymes are sorted into lysosomes as a result of binding to ____________ receptors
mannose-6-phosphate
which specific cell junction type is most responsible for delineating membrane domains that are required for cell polarity?
Adherens junctions
Desmosomal junctions
Gap junctions
Hemidesmosomal junctions
Tight junctions
Tight junctions (zona occludens) seal the apical aspects of the epithelial cell, separating the apical domain from the basolateral domain.
The ZZ mutation is believed to cause alpha-1-antitrypsin to
form intracellular aggregates
FOBD: give 3 major components within the thoracic cavity.
pleura , lungs, mediastinum
FOBD: what are the origin and insertion sites of external and internal intercostal muscles?
external: originates from tubercules , inserts into costal cartilages
internal: originates from sternum , inserts into angle of ribs
FOBD: What are the thoracic levels at which the Inferior Vena Cava (IVC), esophagus , and Aorta pierces through the diaphragm? What nerves innervate the diaphragm (mnemonic)?
IVC at TVIII , Esophagus at TX , Aorta at TXII .
"Phrenic C3,4,5 keeps you alive" --> innervates the diaphragm
FOBD: what are the importances of the horizontal (thoracic) plane? (3). Which Thoracic vertebrae and which rib does it pass through?
The horizontal (thoracic) planes passes through the sternal angle at rib II and TIV/TV .
It marks:
- separates superior mediastinum from inferior mediastinum
- marks the carina
- marks where the aortic arch begins and end
what is the cytoskeleton involved in focal Adhesion?
Actin is involved in focal Adhesions.
how do pmnl recognize microorganisms?
Polymorphic Nuclear Leukocytes sense microorganisms by having 4-methionine receptors
How do listeria and legionellea pneumophilia evade lysosomal degradation?
(Dr. clive Robert's notes week 4 p. 18)
Listeria enters cells by binding epithelial cadherin . It alters actins to create structures that allow cell cell transfer
Legionella penumophilia causes endosome to fuse with ER vesicles instead, and acquires ER markers instead
________ ___________ are located in both the cytoplasm and the nucleus where they act as architectural scaffolds to maintain cell and nuclear structure.
intermediate filaments
_____ is important in tissue segregation during development (eg.neural tube formation)
(Roskelley lecture p.12 )
Cadherin is important in tissue segregation because of their homophilic binding.
neural N-cadherin expressing cells will only exclusively bind to other neural N-cadherin expressing cells,
whereas ectodermal epithelial E-adherin expressing cells will bind exclusively to each other as the neural tube separates from the overlying ectoderm during neurulation
As a result, in the surface epithelium, you will find a lot of E-cadherin ,and in the neural tube, you will find a lot of N-cadherin
How is clavulin co-administered with penicillin to solve the problem with bacterial resistance?
clavulin is co-administered as a decoy, although clavulin in itself has minimal anti-bacterial activity
in the case of microtubules, the hollow tube like structure allows them to
withstand force
Mutations in alpha-1-antitrypsin can occur that lead to reduced activity, despite normal secretion and normal serum levels of the protein . T/F?
T.
Different mutations in the same gene can cause different outcomes. This is the concept of phenotypic heterogeneity, as discussed in PRIN Week 3. One mutation in the alpha-1-antitrypsin gene may cause the protein to misfold and accumulate in the ER, while another mutation in that gene can cause the protein to be secreted normally, although it may have reduced enzymatic activity. (Other mutations may not cause any abnormal phenotypic outcomes.)
what is the mechanism for resistance against penicillan?
beta lactamase
Dr. Clive Roberts. The Cell (lecture 1) What is the name of the phospholipid that majorly forms the bilayer? Also, ______ makes regions less flexible and less permeable.
phosphatidylcholine
cholesterol
What are lipid rafts?
they are an area of rich cholesterol and rich transmembrane proteins. They serve as an organizing center for signalling molecules.
Give 3 functions of the SER.
1. lipid biosynthesis
2. detoxification of lipid-soluble drugs (via cytochromes P450)
3. Sequestration of calcium (muscle - sarcoplasmic reticulum)
Give 2 functions of peroxisomes.
1. oxidize and detoxify phenols, alcohol, fatty acids
2. early steps in the production of myelin
What is the MOST important function of the citric acid cycle?
It creates a proton gradient in the mitochondria (high proton concentration in intermembranous space), so H will run back to the cytoplasm and ATP will be produced by ATP synthase.
Rank the size of the cytoskeleton of the body in ascending order. List one function of each type of cytoskeleton.
mnemonic: AIM.
Actin: contractile filaments
Intermediate filament: made by keratin that makes skin
Microtubules: pulls apart chromosome in anaphase; ALSO flagelle and cilia
The CELL III: targetting and secretion. ______ of amino acid dictates aspects oof processing, correct targetting, asymmetrical orientation in membranes. For example, transmembrane proteins have specific domains (typically, _____ _____) that associate with membrane lipids in the bilayer. Explain why.
sequence
alpha helix
Transmembrane domains are made of alpha helix that are hydrophobic, so that they are compatible with the hydrophobic core of the lipid bilayer
Define a pre-protein and a pro-protein.
A pre-protein is a polypeptide that still has a signal sequence bound to it
a pro-protein is an inactive precursor polypeptide that contains many proteins, and when cleaved, will be activated . Cleavage occurs when you need that protein product. eg. POMC
explain how ribosomes get bound to the RER.
ribosomes get bound to the RER when they are translating a polypeptide with a signal sequence destined for export.
Signal Recognition Peptide (SRP) binds to the signal sequence on the growing polypeptide, then brings the ribosome-polypeptide to the docking protein on the RER.
After the polypeptide enters the ER lumen, the signal peptide is cleaved.
How is a double--pass transmembrane protein created? Signal sequences are usually found on which terminal? Are signal sequences cleaved?
There is a start-transfer sequence and a stop-transfer sequence on the polypeptide.
Explanation:
1. Start sequence causes the SRP to bring the peptide to the RER
2. Translation continues until the stop sequence is encountered; the translocation channel is disassembled
3. translation continues in the cytoplasm; both start and stop sequences are not cleaved so they stay embedded within the ER membrane
signal sequences are usually found on the N terminal, they are cleaved.
But start and stop sequences are not cleaved
Describe the events that happen in a nascent protein that was just synthesized into the ER.
1. Chaperones (heat shock proteins ) help ensure proper folding.
2. SH are oxidized so S-S bonds are formed correctly
3. Glycosylation
What is the mechanism of cystic fibrosis?
The CFTR gene codes a multi-pass transmembrane protein that is a gated channel for chloride ions.
The mutation causes the protein product to be recognized as misfolded and thus degraded.
But actually there is nothing wrong with the protein itself. It is just not recognized as functional
Why is glycosylation important (4 functions)? Where is it carried out?
Glycosylation is important because
1. sorting
2. increased half-life (protects the protein from degradation)
3. specific binding functions
4. The polysaccharide part is important for defining the function of many glycoproteins.
Depending on the type of glycosylation, it can either occur in the ER or the golgi
what are the two pathways of vesicle secretion? In which pathway are the products stored?
the two pathways are constitutive and regulated. Products are stored in the regulated pathway, because there is a delay between when products are produced and when they are released.
Explain how newly synthesized lysosomal hydrolases are targeted towards lysosomes.
a sequence on the newly synthesized lysosomal hydrolases causes Golgi to add M6P to it, and so at trans golgi, M6P receptors that can recognize this M6P will bind to it and also link it to clathrin, and it will be sent to the lysosome
What are the three ways degradation of proteins can occur? Explain which ways are used in different situations.
1. proteasome (cytoplasmic, intracellular proteins that are old or defective)
2. lysosome (endocytosed, extracellular, or whole organelles)
3. proteinases (extracellular)
Cell polarity: What are the determinants of cellpolarity?
1. cytoskeleton
2. cell junctions (adhesion complexes)
Why is apical/ basal polarity in hepatic lobules more complex? What do they secrete respectively?
because now the apical border is enclosed between cell to cell (both cells secrete into this bile canaliculi) , and on either sides of the canaliculi are sealed by tight junctions.
The basal sinusoidal layer secretes to blood (endocrine secretion)
The apical biliary layer secretes bilirubin, bile salts, cholesterol (exocrine secretion)
What are the 3 components of the cytoskeleton? Describe their function and rank their diameter in ascending order.
A<I<M
Actin: adhesion of cells, contractile force, and microvilli
Intermediate Filaments: tensile Strength, Structure, Stronger (cell-cell, cell-ECM anchors)
Microtubule: cilia, Moves stuff around within the cell
What is the MTOC?
It is the MicroTubule Organizing Center. It anchors the minus end of MT .
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Cartes-fiches
Dr. Clive Roberts. The Cell (lecture 1) What is the name of the phospholipid that majorly forms the bilayer? Also, ______ makes regions less flexible and less permeable.
phosphatidylcholine
cholesterol
What are lipid rafts?
they are an area of rich cholesterol and rich transmembrane proteins. They serve as an organizing center for signalling molecules.
Give 3 functions of the SER.
1. lipid biosynthesis
2. detoxification of lipid-soluble drugs (via cytochromes P450)
3. Sequestration of calcium (muscle - sarcoplasmic reticulum)
Give 2 functions of peroxisomes.
1. oxidize and detoxify phenols, alcohol, fatty acids
2. early steps in the production of myelin
What is the MOST important function of the citric acid cycle?
It creates a proton gradient in the mitochondria (high proton concentration in intermembranous space), so H will run back to the cytoplasm and ATP will be produced by ATP synthase.
Rank the size of the cytoskeleton of the body in ascending order. List one function of each type of cytoskeleton.
mnemonic: AIM.
Actin: contractile filaments
Intermediate filament: made by keratin that makes skin
Microtubules: pulls apart chromosome in anaphase; ALSO flagelle and cilia
The CELL III: targetting and secretion. ______ of amino acid dictates aspects oof processing, correct targetting, asymmetrical orientation in membranes. For example, transmembrane proteins have specific domains (typically, _____ _____) that associate with membrane lipids in the bilayer. Explain why.
sequence
alpha helix
Transmembrane domains are made of alpha helix that are hydrophobic, so that they are compatible with the hydrophobic core of the lipid bilayer
Define a pre-protein and a pro-protein.
A pre-protein is a polypeptide that still has a signal sequence bound to it
a pro-protein is an inactive precursor polypeptide that contains many proteins, and when cleaved, will be activated . Cleavage occurs when you need that protein product. eg. POMC
explain how ribosomes get bound to the RER.
ribosomes get bound to the RER when they are translating a polypeptide with a signal sequence destined for export.
Signal Recognition Peptide (SRP) binds to the signal sequence on the growing polypeptide, then brings the ribosome-polypeptide to the docking protein on the RER.
After the polypeptide enters the ER lumen, the signal peptide is cleaved.
How is a double--pass transmembrane protein created? Signal sequences are usually found on which terminal? Are signal sequences cleaved?
There is a start-transfer sequence and a stop-transfer sequence on the polypeptide.
Explanation:
1. Start sequence causes the SRP to bring the peptide to the RER
2. Translation continues until the stop sequence is encountered; the translocation channel is disassembled
3. translation continues in the cytoplasm; both start and stop sequences are not cleaved so they stay embedded within the ER membrane
signal sequences are usually found on the N terminal, they are cleaved.
But start and stop sequences are not cleaved
Describe the events that happen in a nascent protein that was just synthesized into the ER.
1. Chaperones (heat shock proteins ) help ensure proper folding.
2. SH are oxidized so S-S bonds are formed correctly
3. Glycosylation
What is the mechanism of cystic fibrosis?
The CFTR gene codes a multi-pass transmembrane protein that is a gated channel for chloride ions.
The mutation causes the protein product to be recognized as misfolded and thus degraded.
But actually there is nothing wrong with the protein itself. It is just not recognized as functional
Why is glycosylation important (4 functions)? Where is it carried out?
Glycosylation is important because
1. sorting
2. increased half-life (protects the protein from degradation)
3. specific binding functions
4. The polysaccharide part is important for defining the function of many glycoproteins.
Depending on the type of glycosylation, it can either occur in the ER or the golgi
what are the two pathways of vesicle secretion? In which pathway are the products stored?
the two pathways are constitutive and regulated. Products are stored in the regulated pathway, because there is a delay between when products are produced and when they are released.
Explain how newly synthesized lysosomal hydrolases are targeted towards lysosomes.
a sequence on the newly synthesized lysosomal hydrolases causes Golgi to add M6P to it, and so at trans golgi, M6P receptors that can recognize this M6P will bind to it and also link it to clathrin, and it will be sent to the lysosome
What are the three ways degradation of proteins can occur? Explain which ways are used in different situations.
1. proteasome (cytoplasmic, intracellular proteins that are old or defective)
2. lysosome (endocytosed, extracellular, or whole organelles)
3. proteinases (extracellular)
Cell polarity: What are the determinants of cellpolarity?
1. cytoskeleton
2. cell junctions (adhesion complexes)
Why is apical/ basal polarity in hepatic lobules more complex? What do they secrete respectively?
because now the apical border is enclosed between cell to cell (both cells secrete into this bile canaliculi) , and on either sides of the canaliculi are sealed by tight junctions.
The basal sinusoidal layer secretes to blood (endocrine secretion)
The apical biliary layer secretes bilirubin, bile salts, cholesterol (exocrine secretion)
What are the 3 components of the cytoskeleton? Describe their function and rank their diameter in ascending order.
A<I<M
Actin: adhesion of cells, contractile force, and microvilli
Intermediate Filaments: tensile Strength, Structure, Stronger (cell-cell, cell-ECM anchors)
Microtubule: cilia, Moves stuff around within the cell
What is the MTOC?
It is the MicroTubule Organizing Center. It anchors the minus end of MT .
Cell junctions aka what? what are the three components of these cell junctions?
cell junctions aka adhesion complexes.
Three components are :
1. Receptor
2. Linker
3. Cytoskeleton
cell-cell junctions are found on the apical/basal side of cell.
which type of junction does cadherin belong to? How did cadherins got their name? why are they important during neural development?
Cadherin belongs to Zona Adherens.
Cadherins stands for Calcium Dependent Adherence
They are important during neurulation because of their unique property that they will exclusively only bind to each other who has the same type of receptor.
eg. neural N-cadherin expressing cells will only bind to other neural N-cadherin expressing cells, and Ectodermal E-cadherin expressing cells will only bind to other Ectodermal E-cadherin expressing cells. This is the basis of their role in tissue segreagation during development. This unique property is called Homophilic binding
Which junction does Catenins belongs to? what are their two functions?
Catenins belong to Zona Adherens.
Catenins is the linker protein for this junction, and when it is not doing that, it also plays a role in signal transduction (it moves from the cytoplasm to the nucleus and regulates gene expression)
Where can desmosomes be found? What cytoskeleton are they linked to?
Desmosomes can be found anyhwere along the entire lateral surface between two adjacent cells.
They are linked to stable intermediate filaments
Where can gap junctions be found? Gap functions are made by ______, which is formed by 6 proteins.
Gap junctions can be found anywhere along the lateral surface between two adjacent cells.
Gap junctions are made by connexons (one on each side of the gap), and connexons are formed by 6 proteins .
What is the function of hemidesmosomes? Explain why hemidesmosomes are called heterophilic.
The function of hemidesmosomes is to anchor cells to ECM (Note: not to matrix)
THe receptors of hemidesmosomes are heterophilic because they bind to ECM glycoproteins rather than the same receptor protein on neighboring cells.
What is the function of hemidesmosomes? Explain why hemidesmosomes are called heterophilic.
The function of hemidesmosomes is to anchor cells to ECM (Note: not to matrix)
THe receptors of hemidesmosomes are heterophilic because they bind to ECM glycoproteins rather than the same receptor protein on neighboring cells.
What are Focal adhesions mainly used for? What is the cytoskeleton that they bind to? The linker proteins they have are both _____ and __________
Focal adhesion junctions are mainly used for cell migration (highly dynamic junctions they binds and unbinds to ECM quickly). They bind to actin filaments. The linker pteins are both structural and enzymatic (kinases that can assemble and disassemble the complex)
Give a summary diagram of "cell polarity"
here you go
CELLULAR TARGETS OF DRUG THERAPY. STAN BARDAL. Identify cellular targets of drug therapy.
Cell wall
Ribosome
Inhibit RNA synthesis
inhibit DNA synthesis (DNA gyrase and purine synthesis inhibitors)
(ANTIFUNGAL) glucan synthase inhibitor (cell wall)
(ANTIFUNGAL) Ergosterol inhibitors (ergosterol is part of cell membrane)
Explain the mechanism of action of Amoxicillin, Azithromycin, and Trimethoprim/Sulfamethoxazole (Septra).
Amoxicillin is a cell wall synthesis inhibitor. It reacts with transpeptidase, a bacterial protein that creates cross-links within layers of the cell wall, such that the cell wall is cannot be completed, thus bacteria cell dies.
Azithromycin is a ribosome inhibitor. It binds either the 50S or 30S to slow down translation, thus achieving a bacteriostatic effect.
Trimethoprim/Sulfamethoxazole (Septra) inhibit purine synthesis at two distinct steps, by mimicking the substrate and competing for the enzyme (because bacteria must synthesize their own purine, and can't obtain it from diet)
PABA --(a)--> DHF ---(b)--> THF --> Purines. These two analogues act at steps a and b respectively.
a. Dihydropteroate synthase
b. DHF reductase inhibitors
Drugs used to treat fungal infections target ergosterol in which 2 ways?
1. inhibiting enzymes that create ergosterol (squalene epoxidase, CYP450)
2. directly binding to ergosterol
- since ergosterol is part of the fungal cell membrane, without ergosterol, the fungal cell will be destabilized.
describe and give examples of how drugs can act both synergistically and antagonistically
Synergistic effect:
eg. Trimethoprim and Sulfamethoxazole. Their cumulative effect is greater than the sum of each individual drug added together.
Antagonistic effect:
eg. when ribosomal inhibitors are administered with cell wall synthesis inhibitors. Cell wall synthesis inhibitors work best in actively-dividing cells, but ribosomal inhibitors are bacteriostatic, pretty much guaranteeing the cell won't be actively dividing.
PABA --(a)--> DHF ---(b)--> THF --> Purines. What are enzymes a and b?
a. Dihydropteroate synthase
b. DHF reductase
what are caveolae?
Caveolae are regions of the cell membrane that are especially rich in cholesterol and sphingolipids. These regions are involved in clathrin-independent endocytosis.
Mycobacterium tuberculosis bacteria are able to survive in the host because:
they are adapted to survive and replicate inside phagocytic vesicles and lysosomes.
After the bacteria are phagocytosed by macrophages, the bacteria prevent phagosome-lysosome fusion and multiply in the phagosome until the macrophage bursts
Which of the following does not occur in mitochondria?
DNA replication
Glycolysis
Oxidative phosphorylation
Pyruvate decarboxylation
Tricarboxylic acid (TCA) cycle
a) Mitochondrial DNA is replicated in mitochondria.
*b) Glycolysis occurs in the cytoplasm.
Which of these molecular species is involved in targeting a secretory vesicle to the plasma membrane?
serum protein that is improperly folded during synthesis in the hepatocyte would normally be:
I. retained in the endoplasmic reticulum
II. retained in the Golgi apparatus
III. secreted then endocytosed and degraded in the lysosome
IV. transported to the cytoplasm and degraded in the lysosome
V. transported to the cytoplasm and degraded in the proteasome
