Unit 3 Flashcards
1
Q
what is the endoplasmic reticulum?
A
single compartment from the outer layer of nuclear envelope into the cytoplasm
2
Q
what is the most extensive organelle, making up 50% of the plasma membrane?
A
endoplasmic reticulum
3
Q
what is the sarcoplasmic reticulum
A
endoplasmic reticulum of striated (heart) and skeletal muscle
4
Q
describe the structure of the endoplasmic reticulum
A
interconnected array of tubules and cisternae with a single lipid bilayer
5
Q
what are the types of ER
A
rough
smooth
sarcoplasmic
6
Q
what’s the difference between rough and smooth ER
A
-
ROUGH
- has ribosomes
- makes proteins
- protein sacs bud off as transport vesicles to golgi apparatus for processing and then sent to plasma membrane or another organelle
-
SMOOTH
- no ribosomes
- makes lipids
- carbohydrate metabolism
- detoxification of natural metabolism products/ products and drugs
- found abundantly in the liver
- regulates calcium concentration in muscle cells for contraction
7
Q
which organ produces most proteins?
A
liver
8
Q
what are the subunits of RER?
A
- small ribosomal subunits: read RNA
- large subunits: join amino acids to form a polypeptide chain
9
Q
what cells secrete so many proteins?
A
b-lymphocytes secrete antibodies
beta cells of the pancreas, produce hormones
10
Q
what is glycosylation?
A
addition of a sugar molecule.
11
Q
which organelle recognizes destination label attached to polypeptide and amino acids?
A
rough endoplasmic reticulum
12
Q
list the functions of both the RER & SER
A
RER:
- protein manufacture
- protein targeting
SER
- drug detoxification
- steroid production
- calcium storage and release
13
Q
How does RER produce proteins?
A
via ribosomes in a process known as translation
14
Q
how does the RER target proteins?
A
by a signal sequence at their amino (N) terminus that is often aa(15-60), which enables cellular transport machinery and correct positioning of the protein inside the cell
15
Q
how does the SER produce lipids?
A
via enzymes embedded in the membrane of the SER, which form the lipids of membranes
16
Q
how does the SER eliminate drugs?
A
it has CYP450 enzymes, which have a role detoxification of xenobiotics, cellular metabolism and homeostasis.
17
Q
define sarcomere
A
complicated unit of striated muscle tissue
or
repeating unit between Z lines
18
Q
what are skeletal muscle composed of?
A
muscle fibers aka myofibers
19
Q
how does SER regulate calcium storage and release
A
Calcium is pumped into the SER by active transport and released in response to hormonal signals. This is particularly important in muscle cells where the SER is so prominent it has a special name, the sarcoplasmic reticulum.
20
Q
make 4 notes on the golgi apparatus
A
1- flattened membrane enclosed disc-shaped-sacs
2- located near the nucleus
3- cis face (entry) trans face (exit)
4- proteins arrive to it in transport vesicles
21
Q
what happens to transport vesicles upon their arrival at the golgi apparatus?
A
they fuse with golgi, where they are processed, then pinch off through the trans face and move to fuse with plasma membrane
22
Q
where is golgi found abundantly?
A
in secretory cells, like antibody secreting plasma b cells
23
Q
what is exocytosis?
A
process by which vesicles release their contents into the cell’s exterior
24
Q
what’s the difference between a constitutive secretory pathway and a regulated secretory pathway?
A
constitutive: secretory vesicles transport soluble proteins that are released from the cell continually
whereas, regulated pathway, secretory vesicles store soluble proteins for when they are needed just like in mast cells which produce histamine
25
what are the functions of golgi apparatus?
* secretory pathways
* lysosome formation
* protein modification and sorting
26
how does the golgi apparatus forms lysosomes? and provide an example
by the fusion of vesicles that have budded off from the trans-Golgi. The sorting system recognizes address sequences in the hydrolytic enzymes and directs them to growing lysosomes
**example:** mannose-6-phosphate label is added to proteins destined for lysosomes and packaged into vesicles that bud off from trans golgi
27
provide an example how how golgi is involved in protein modification and sorting
it is involved in post translational modification, for instance, addition of carbohydrates or phosphorylation of oligosaccharides
28
the golgi apparatus modifies lipids and proteins to produce
1-
2-
3-
1- glycolipids
2- glycoproteins
3- proteoglycans
29
what are the 3 types of golgi vesicles?
* exocytic vesicles (constitutive)
* secretory vesicles (regulated)
* lysosomal vesicles
30
differentiate the 3 golgi vesicle pathways
exocytic vesicles → continual/constitutive extracellular release (plasma b cells)
secretory vesicles → regulated, stored until signalled for extracellular release (neurotransmitter release from neuron)
lysosomal vesicle → has degradative enzymes for proteins/ribosomes (digestive proteases)
31
what is cell cycle?
The cell cycle consists of a series of steps during which the chromosomes and other cell material double to make two copies.
32
which phase makes most of the cell cycle?
**interphase G1,** the cell grows physically and increases the volume of both protein and organelles.
33
briefly explain the phases of cell cycle
Initially in **G1 phase**, the cell grows physically and increases the volume of both protein and organelles. **In S phase**, the cell copies its DNA to produce two sister chromatids and replicates its nucleosomes. **G2** phase involves further cell growth and organisation of cellular contents. **M phase, is the mitosis phase where cell actively divides**
34
at what level of the body do drugs function?
cellular
35
what are the principles of drug action?
* act at specific receptors (internal/external)
* interfere with physiological or biochemical processes of pathogen/body
* bind to a single type of receptor
* enter cells by diffusion though membrane
36
what are the three types of diffusion used by drugs to enter the cell?
* facilitated diffusion
* active transport
* pinocytosis
37
what types of drugs are there, based on the responses they produce?
* agonist, bind to receptor to stimulate a response
* antagonist, block receptors to prevent unwanted response (killing pathogens by producing unwanted response)
38
what is the mechanism of action of penicillin/vancomycin/cephalosporins
disrupt formation of cell wall
39
what is the mechanism of action of sulfonamide/trimethoprim
inhibits folic acid metabolism, thus preventing growth
40
what is the mechanism of action of tetracyclines/streptomycin/chloramphenicol/erythroycin?
bind to 70s ribosome, blocking protein synthesis
41
what is the mechanism of action of polypeptide antibiotics
interact with phospholipids and disrupts outer membrane
42
what is the mechanism of action of quinolones?
affects DNA formation
43
what is the mechanism of action of rifampin
affect mRNA formation
44
what is the general mechanism of action of anticancer drugs
interferewith DNA replication, translation and protein synthesis and folding in ER, protein glycosylation in Golgi, and metabolic activity in mitochondria
45
what is the mechanism of action of the anticancer drug, tamoxifen?
induces gonadotrophin release by occupying estrogen receptors in the hypothalamus, thereby interfering with feedback mechanisms
46
what is a cytoskeleton
dynamic, 3D structure that fills the cytosol
47
what is the difference of cytosol and cytoplasm?
Cytosol is known as the matrix of the cytoplasm. It surrounds the cell organelles in eukaryotes. In prokaryotes, all the metabolic reactions occur here. Thus, we can infer that while cytosol is the fluid contained in the cell cytoplasm, cytoplasm is the entire content within the cell membrane
48
what is the difference between cytoskeleton and cytoplasm?
The cytoplasm consists of everything inside the cell membrane of the cell, excluding the nucleus in a eukaryotic cell. The cytoskeleton is a cellular "skeleton" that criss-crosses the cytoplasm.
49
what are the three cytoskeleton filaments?
microfilaments
microtubules
intermediate filaments
50
what is the composition of the cytoskeleton?
protein polymers, that are made up of identical subunits that allow rapid reorganization
51
how are the different filaments of the cytoskeleton formed?
by polymerisation of a distinct type of protein subunit
52
provide an example of a drug that targets the ER/Golgi complex
rapamycin (sirolimus), used as a prophylactic treatment in kidney allograft recipients
53
what does rapamycin target in the ER/Golgi complex?
serine-threonine-protein kinase mTOR/T cells
54
what is the structure and function of microtubules?
hollow tubes made up of alpha and beta tubulins that are a part of the cytoskeleton
they provide proper shape and keep organelles in place
55
what class of drugs are colchicine and paclitaxel?
microtubule drugs
56
what are the classes of microtubule drugs?
* tubulin binding
* microtubule-stabilizing
* microtubule-destabilizing
57
what is the mechanism of action of tubulin binding drugs?
inhibit microtubule dynamics that are required for DNA segregation and cell division
indication: cancer
58
what is the mechanism of action of microtubule stabilizing drugs?
prevent the dissociation of tubulin subunits and block mitosis which stabilizes GDP bound tubulin
indication: breast cancer/ovarian cancer
59
what is the mechanism of action of microtubule destabilizing drugs?
promote disassembly of microtubules, causing a change in organelle location and blocks wbc migration thus reducing inflammation
indication: inflammatory conditions (arthritis/gout)
60
what is the significance of lipids in the cell membrane?
they provide good drug targets (receptors/channels/receptors)
61
draw the phospholipid bilayer (plasma membrane)
62
what are the 4 different endocytic pathways?
* budding
* fission
* fusion
* direct transport
63
TRUE OR FALSE:
lipids in the plasma membrane have asymmetrical organization
TRUE
64
give 5 examples of lipids in the plasma membrane
phosphatidylethanolamine
phosphatidylserine
phosphatidylglycerol
phosphatidic acid
phosphatidylcholine
glycolipids
cholesterol
65
what is the function of endocytosis?
* uptake of extracellular nutrients (iron-transferin/fat-ldl/oncogenic signaals-cancer)
* cell recovery (protein/lipids)
* cholesterol homeostasis (LDL receptor)
66
what is the extracellular pH
7.4
67
what is anaemia and haemochromatosis?
anaemia: lack enough healthy red blood cells to carry adequate oxygen to your body's tissues
haemochromatosis: an inherited condition where iron levels in the body slowly build up over many years
68
what is the function of iron in cells? how does it enter the cell?
* carry oxygen in the hemoglobin of red blood ***cells*** throughout your body so your ***cells*** can produce energy.
* heme synthesis, which forms haemoglobin, a protein found in red blood cells.
69
what is the epidermal growth factor, and what does it do?
common mitogenic factor that stimulates the proliferation of different types of cells, especially fibroblasts and epithelial cells. EGF activates the EGF receptor (EGFR/ErbB), which initiates, in turn, intracellular signaling.
70
1- what is EGF internalization?
2- what is the major mechanism by which EGF internalization is carried out?
1. Activated EGF (epidermal growth factor) receptors are removed from the cell surface via endocytosis and subsequent degradation in the lysosome.
2. clathrin-mediated endocytosis (CME), whereby the receptor is removed from the surface via clathrin-coated pits and then routed to the early endosomes
71
which digestion product do these proteins carry
beta globulins
alpha globulins
albumin
beta globulins → cholesterol/triglycerides
alpha globulins → phospholipids
albumin → free fatty acids (FFA)
72
fats being hydrophobic, they need specialized transport by \_\_\_\_\_\_\_
lipoprotein complexes
73
plasma lipids are transported to become:
1- soluble
2- recognizable
74
cholesterol/triglycerides/phospholipids are carried as complexes along with proteins known as \_\_\_\_\_\_\_
apoproteins
75
what are the 3 apoproteins?
APO E
APO C
APO B
76
what is the function of LDL
Low-density lipoproteins (LDL) carry cholesterol from the liver to the rest of the body.
Cells latch onto these particles and extract fat and cholesterol from them.
carries 70% of body's cholesterol
77
what is APO B protein
primary lipoprotein that is the structural backbone of LDL, synthesized in the liver where it interacts with other molecules to form VLDL
78
what is are the properties of VLDL?
* triglyceride rich
* LDL precursor
79
what is hypercholesterolemia?
overproduction or overclearance of APO B, increasing the deposition of cholesterol in the endothelium leading to cardiovascular disease or atherosclerosis
80
what are the 3 lipoproteins?
* VLDL
* LDL
* LPa
81
define autophagy
degredation of old and damaged organelles in membrane in the lysosome
82
what's the difference between retrograde transport and anterograde transport?
When substances are going toward the axon tip, it is known as anterograde transport, and when they are going toward the cell body, it is known as retrograde transport
83
provide notes about insulin
Insulin is a peptide hormone
produced by beta cells of the pancreatic islets encoded in humans by the INS gene.
It is considered to be the main anabolic hormone of the body.
84
what is the mechanism of action of insulin
Insulin helps keep the glucose in blood within a normal range. It does this by taking glucose out of the bloodstream and moving it into cells throughout the body.
85
how is insulin produced in the body?
When you digest your food, carbohydrates convert to glucose. The glucose is directed into your bloodstream, which causes your blood glucose levels to rise. This is what sends the message to your pancreas to produce insulin, which instructs your cells to absorb the glucose traveling through your bloodstream
86
give one example for a direct membrane traffic disease and an indirect one
* direct: neimann pick type c (lysosomal storage)
* indirect: cystic fibrosis (CFTR traffic)
87
1- what is the function of CFTR?
2- what happens to CFTR in cystic fibrosis patients?
1- regulating the proper flow of chloride and sodium (a component of salt) in and out of the cell membranes in the lungs and other organs
2- CFTR transport is blocked in the endoplasmic reticulum
88
differentiate eukaryotic and prokaryotic cells
89
why do cells need endocytosis?
because molecules required for cell function are polar and large and can't diffuse through the hydrophobic portions of the plasma membrane by passive diffusion
90
what are the types of endocytosis?
* pinocytosis
* receptor mediated (clathrin mediated)
* phagocytosis
91
what is pinocytosis?
when small vesicles take dissolved material in liquids.
e.g. saprophytic fungi
92
what is clathrin mediated endocytosis?
a vesicular transport event that facilitates the internalization and recycling of receptors engaged in a variety of processes, including signal transduction (G-protein and tyrosine kinase receptors), nutrient uptake and synaptic vesicle reformation.
e.g viruses → LDL uptake (coated vesicle)
93
what is phagocytosis?
ingestion of bacteria or other material by phagocytes and amoeboid protozoans
94
what are the steps of phagocytosis?
1- engulfment
2- phagosome formation
3- digestion in phagolysosome
4- expulsion of undigested materials
95
phagocytosis acts on particles that are bigger than _____ nM
250 nM
96
what are the cells that are capable of phagocytosis?
* neutrophils
* monocytes
* macrophages
* mast cells
* dendritic cells
97
what is the difference between phagocytosis/endocytosis/autophagy?
phagocytosis: external pathogens
endocytosis: receptor recycling
autophagy: excess/old organelles
98
what are the symptoms of dysfunctional mitochondria
* profound weakness
* encephalopathy
* seizures
* liver failure
* poor growth
* neurological symptoms
* muscle weakness
99
what is the site of oxygen utilization?
peroxisomes
100
why are peroxisomes so named?
because they contain one or more enzymes that use oxygen to remove hydrogen from organic substrates in oxidative reactions hat produce hydrogen peroxide
## Footnote
RH2+O2→ R + H2O2
101
what is the function of endosomes?
* regulation of cell surface protein expression
* internalization of nutrients
* uptake and digestion
* exploit pathogens
102
which organelle produces lysosomes?
Golgi
103
what are the hydrolytic enzymes of lysosomes?
lipases
nucleases
carbohydrases
proteases
104
how are lysosomal diseases caused?
deficiency of an enzyme required for lipid and glycoprotein metabolism, for example resulting in gaucher's disease
105
what is ambroxol indicated for and what is its mechanism of action?
it is indicated for parkinson's, it increases the activity of glucocerebrosidase (enzyme replacement therapy)
106
what causes neurodegenerative disease?
accumulation of misfolded proteins in the cytosol and nucleus
107
what causes neurodegenerative disease?
accumulation of misfolded proteins in the cytosol and nucleus
108
what enzyme is accumulated in huntington's disease?
polyQ
109
what protein is misfolded in familial amyotrophic lateral sclerosis?
superoxide dismutase 1
110
what protein is misfolded in
1- alzeheimer
2- parkinson's
3- spongiform encephelopathies
4- familial amyloiditic polyneuropathy
1. amyloid beta peptide
2. alpha synuclein
3. prion proteins
4. tranthyretin
111
what is the main function of the mitochondria?
cellular respiration, convert energy usable by cells (ATP)
112
why does excercise increase the number of mitochondria?
because cells adapt to higher demand of energy
113
what are the main regions of the mitochondria
* outer membrane
* intermembrane space
* inner membrane
* matrix
114
what is the function of the inner membrane of the mitochondria?
form cristae that increase surface area thus enhance ATP production (high demand mitochondria = more cristae)
115
what is the function of the intermembrane space of mitochondria?
it has cytochrome C which is a component of electron transport chain across inner membrane
apoptosis
116
what enzymes does the matrix of the mitochondria have?
krebs cycle, pyruvate oxidation, and other enzymes that encode tRNA/ (37genes)
117
what are plasmids?
small ring shaped DNA molecules containing a few genes
118
what is the function of plasmids?
* fertility: transfer genetic material
* resistance: from antibiotics
* degredative: digestion of organic compounds
* virulence: turn bacterium to pathogen
119
what are the mechanisms by which plasmids transfer genetic material? (horizontal gene transfer)
* transformation
* transduction
* conjugation
120
which bacteria produces insulin?
E.coli
121
what chemical reactions take place in the cytosol?
* early nutrient breakdown
* glycolysis
* protein manufacture
* signalling transduction
122
what's the difference between endothelium and epithelium?
epithelial cells line both internal surfaces and external surfaces of the body whereas endothelial cells line the internal surfaces of the components of the circulatory system.
123
describe the two regions of the phospholipid bilayer in terms of permeability
polar molecules: ions, peptides, charged drugs
Apolar: glucose, fats, uncharged drug
124
a solution that has the same solute concentration as compared to another one is known as
isotonic solution
125
the main cause of the resting membrane potential
differential distribution and relative permeabilities of NA & K ions
Also think of important solutes: Glucose etc . Extracellular Concentration of Calcium is 1.5-2.0mM Massive difference between intracellular and extracellular calcium
126
what is responsible for 1/5 of the cell's energy expenditure?
ATPase
127
what is the function of ATPase?
* ATPase helps maintain resting potential,
* effect transport, and regulate cellular volume.
* It also functions as a signal transducer/integrator to regulate MAPK pathway, ROS, as well as intracellular calcium. In most animal cells, the Na+
128
what are the membrane proteins?
intrinsic, such as ion channels, receptors for neurotransmitters, pumps and transports (CFTR)
extrinsic, such as recognition and adhesion molecules
129
what's the difference between an ion pump and an ion channel?
ion pumps actively transport ions against a concentration gradient, while ion channels allow ions to passively flow down a concentration gradient.
further reading: [Ion channels versus ion pumps: the principal difference, in principle | Nature Reviews Molecular Cell Biology](https://www.nature.com/articles/nrm2668)
130
define ion channels
Ion channels are water-filled pores that allow ions to cross the membrane and move DOWN their concentration gradient.
131
true of false: Individual ion channels are specific to particular ions, meaning that they usually allow only a single type of ion to pass through them.
true
132
what is long q t syndrome
**Long QT syndrome** is an inherited heart problem that affects how your heart beats.
133
what type of receptor is the nicotinic acetylcholine receptor?
ionotropic receptor (ligand-gated)
134
what is the mechanism of action of salbutamol?
Binding to Beta 2 adrenoceptors results in smooth muscle relaxation and opening of the airways
135
what drug class is salbutamol
beta 2 adrenoreceptor agonist
136
true or false
25% of pharmaceutical drugs target receptors
true
137
what types of receptors are in the plasma membrane?
direct: ionotropic: more than one protein/gene
indirect: intracellular: signal is not membrane limited, signal transduction is slower and needs regulation
138
define a kinase
an enzyme that catalyses the transfer of a phosphate group from ATP to a specified molecule
139
what do lipid kinases do?
Lipid kinases phosphorylate lipids in the cell, both on the plasma membrane as well as on the membranes of the organelles
140
how does ß-2 receptor – adrenaline M2 Muscarinic Receptor- acetylcholine work
β adrenergic receptors are coupled to a stimulatory G protein of [adenylyl cyclase](https://en.wikipedia.org/wiki/Adenylyl_cyclase). This enzyme produces the second messenger [cyclic adenosine monophosphate](https://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate) (cAMP). In the lung, cAMP decreases calcium concentrations within cells and activates [protein kinase A](https://en.wikipedia.org/wiki/Protein_kinase_A). Both of these changes inactivate [myosin light-chain kinase](https://en.wikipedia.org/wiki/Myosin_light-chain_kinase) and activate [myosin light-chain phosphatase](https://en.wikipedia.org/wiki/Myosin-light-chain_phosphatase). In addition, β2 agonists open large conductance [calcium-activated potassium channels](https://en.wikipedia.org/wiki/Calcium-activated_potassium_channel) and thereby tend to hyperpolarize airway smooth muscle cells. The combination of decreased intracellular calcium, increased membrane potassium conductance, and decreased myosin light chain kinase activity leads to smooth muscle relaxation and bronchodilation.
141
what types of transporters are there?
**Uniport:** Ca2+ pump
**Symport:** Glucose-Na+ coupled transport in epithelia
**Antiport:** Na+/K+ pump (ALL CELLS)
142
describe the mechanism of **Na+/K+ pump and how it maintains cell membrane potential**
It accomplishes the transport of three Na+ to the outside of the cell and the transport of two K+ ions to the inside. This unbalanced charge transfer contributes to the separation of charge across the membrane.
In order to maintain the cell membrane potential, cells keep a low concentration of sodium ions and high levels of potassium ions within the cell (intracellular). The sodium-potassium pump mechanism moves 3 sodium ions out and moves 2 potassium ions in, thus, in total, removing one positive charge carrier from the intracellular space.
143
true or false
## Footnote
Ca2+ regulation is achieved by both an antiport and a uniport. As a result intracellular Ca2+ is kept very low (~100 nM).
true
144
describe symport action of sodium in the intestine
The sodium driven-glucose symporter uses the potential free energy stored in the sodium electrochemical gradient (low sodium concentration inside the epithelial cells) established by Sodium-potassium pump. Therefore, the sodium influx from the lumen to the epithelial cell is coupled with glucose transport.
145
what is apoptosis?
programmed cell death
146
what is necrosis
Necrosis is **the death of body tissue**.
147
what are the 2 apoptosis pathways
Intrinsic (cell decides) and extrinsic (told by other cells) pathways.
148
true or false
apoptosis is Intimately linked with intracellular Ca2+ and mitochondrial Ca2+ levels
true
149
what is the outcome of apoptosis
Results in blebbing of the membrane and formation of apoptotic bodies which are cleared by immune cells i.e.macrophages
150
what can cause necrosis?
* hypoxia
* ischaemia
* virus
* poison
151
what is the outcome of necrosis?
complete cell death, lysis releases cytotoxic components into the extracellular space which results in inflammation and an immune response.
152
compare and contrast: apoptosis vs necrosis
153
what are the main players in apoptosis
p53
Bcl-2
caspases
cytochrome c
