cellular Flashcards
(113 cards)
1
Q
Mutations in proteins/primary structure changes
A
Cause amino acid sequence changes , can lead to a malfunction of that protein so at a dramatic change only if the change happens in the active site of the protein.
It will change also all the other structure becuase the others depend on the primary, that is a sequence of amino acids along the polypeptide chain.
2
Q
How many structure has a protein?
A
Four, Primary, Secondary, Tertiary and Quaternary
3
Q
Secondary structure of proteins
A
We have 3 types of secondary structure:
alfa-helix: has an helix form thanks to the H bonds betweet every 4 amino acids, that stabilize the structure
beta-sheet: H bonds between parallel parts, are perpendicular to the sheet
Random coli: it may not assume a final structure. this structure allows proteins to not expose the nuclear localization signals, so it will not be recognized e.g ( importin with proteins for spermatogenesis of rats)
Antibody have all the 3 structures
4
Q
Tertiary structure of proteins
A
is the result of all the secondary structure, called globular protein, because it will organize and form a spacial expression, in three dimensions. it depends on the interactions between the R group side chains.
5
Q
Types of interactions between R group side chains
A
Hydrophobic: non polar chain of ami. no acid goes in the core, far away from water
Hydrogen bonds: happens between polar side chain
Ionic bonds : between negative and positive side chain
Disulfide bridge: covalent bond, between S atoms of cysteine amino acid, give stability to the protein
6
Q
Quaternary structure
A
different subunits become associated
7
Q
Protein folding
A
mechanism that to which proteins will reach the active form, This process is helped by chaperone proteins, that shield out bad influence that can cause the protein to no fold properly.
They creat a cylinder with an hat, they open the hat, and the polypetdide chain goes inside, close the hat, the folding happens without interferences, once it reach the correct form, the hat will open and the folded proteins comes out
8
Q
Denaturation of proteins
A
Loss of final structure of proteins that will go back to the previous structure and will not function anymore due to the loss of specificity, due to ph, temperature changes or chemicals. Sometimes it is irreversibile
9
Q
Folded proteins types
A
We have 2 types.
1. FIbrous Proteins: polypeptide chains in fibers or sheet, not soluble in water. have 2 function: 1. Support in structural proteins as collagene and elastin in tendons. 2. Movement as contractile proteins as actin and myosin
- Globular proteins: chain folded in a ring shape, soluble in water. Different function
- Store of amino acids
- Transport proteins as hemoglobin
- Hormone proteins: cellular messenger to mantain homeostasis (insulin-glucagon mechanism)
- Receptors: allow cells to answer to chemical stimuli. each receptor has to recognize is ligand, or we will not have an answer. We have effects by the recognition and interaction between an hormones and a ligand.
- Cholesterol receptors: LDL is endocytosed in vesicles, goes in lysosomes, breaks, free LDL and it will be used in cell.
- Protective proteins: antibodes
- Enzymes
10
Q
Cell membrane is the sum of ….
A
Lipids: foundamental structure
proteins : transporters or channels
carbohydrates: glycolipids, in the extracellular space
11
Q
cell membrane feauters and functions
A
- separate the cell from the non living surrondings
- membrane has selective permeability
- controls what exit and enter, for homeostasis
- protection ad support
- custom
- flexible, allow unicellular organism to move
12
Q
Fatty acids
A
mono carboxylc acids, long hydrocarbon chains, forms lipids
Saturated: No double bonds
Unsaturated: one or more double bonds.
The unsaturated assume different forms, it is important to mantain lipids interactions in the plasma membrane, so its fluidity.
this because double bond cause kinks. Thanks to this kinks, they fit closely together, they have strong attraction betwee them, high melting point so they are solid at room temperature.
the only double bonds that cause kinks is the Cis double bond.
13
Q
Triglycerids
A
reserve of energy.
14
Q
Phospholipids
A
Glycerol + 2 fatty acids chains+ phosphate group
Are Amphipathic= polar and non polar region
head= polar region
tail= non polar region
Glycophospholipids and Sphingolipids(nervous system, sphingosine)
They compose the plasma membrane bilayer: Head face the water, tails on the opposite side
15
Q
Sterols
A
Type of lipids , give charateristic to the plasma membrame as signal transduction, regulation of membrane fluidity.
4 fused rings, tetracyclic system , as for example cyclopnentane perhydro phenanthrene.
cholesterol is a steroid, component of the plasma membrane, it controls membrane fluidity, disturbance in its fluidity cause changes in membranes receptors for nervous/signal trasmission
16
Q
Membranes models
A
- FALSE, Sandwich model :phospholipids bilayer with protein layers on bothe sides. polar molecules cannot enter
- FALSE, Polar pore, same model of before but with pores on the proteins for the passage of polar molecules
- TRUE, Fluid Mosaic. Membrane components are fluid oand capable of movement in the plane,mosaic because a lot of hetoregenous components form the membrane
17
Q
Membrane proteins
A
responsible for the entrace and exit of substances.
two types:
1- Integral or transmembrane proteins, hydrophilic segment in contact with water and hydrophobic segment that allows the protein to run through the bilayer
-Channel proteins: substances across membrane
-Carrier: selectivly intect with molecules to help them to cross it
-Receptors proteins : shaped to bind specific ligands
- Enzymatic proteins:catalyst.
- Peripheral proteins: structural stability and shape of membrane + trasduction pathway
18
Q
Membrane fluidity
A
- Inversely proportional to the saturation of fatty acids tails
- directly to the lenght of the tails
it als depends on:
- percentage of unsaturated fatty acids
- temperature
- cholesterol
non polar bonds between fatty acids= they can move and defomation of the membrane happens
19
Q
Movements of the membrane
A
- Flip Flop: Phospholipid goes from one layer to another in a transversal movement, through flippase
- Ping pong: membrane lipids and proteins drift laterally
- Rotations of the heads
20
Q
Membrane assymetry
A
created at biogenesis in edoplasmatic reticulm, maintened in the time thanks to the movements of the phospholips
Phosphatidylcholine and Sphingomyelin are on external side
Phosphatidylserines on internal side.
in a cell that undergo apoptosis, phosphatidylserine goes on the external side, this is a signal to engulf and digest the dead cell
21
Q
Glycocalyx
A
sum of carbohydrates on the membrane
allow s it to have an identity and to be distinguished from other cells through their carbohydrate antigens
assymetry of membrane
trigger inflammatory response
blood groups antigens
- Antigen A : 0 + N-acetylgalactosammine
- Antigen B: 0 + galactose
- Antigen 0= short sugar chain + fucose
22
Q
Functions of membrane proteins
A
Transporter enzyme activity cell surface receptors cell surface identity marker cell adhesion attachment of the cytoskeleton
23
Q
Membrane proteins + lipid pilayer =
A
transmembrane proteins:
single alfa helix or multiple alfa helix passing through the bilayer
central channel that permits the passage of water and hydrophilic molecules.
Integral proteins, span the entire plasma membrane in this way
peripheral proteins: bonded to others membrane proteins by non covalent weak bonds
anchored proteins: covalent bond with lipid molecules
24
Q
Osmosis
A
hypotonic solutions : water concentration higher than inside cell, water goes in, cell goes boom
hypertonic solutions: lower than cell, water goes outside the cell, cell goes mini
Isotonic solution: equal concentration, equal water movement
25
Carrier Proteins
Required for all small molecules
Grab molecules, conformational change, flip to other side.
Glucose carrier, GLUT 1-6 tissue specific.
2 conformation:
A: ninding site to outside
B: binding site on inside
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Facilitated diffusion
Passage of polar substances by concentration gradient ( high to low concentration)
This involves transporters that recognise the susbtance needing to be trasported. high specificity of trasporters
Apolar molecules goes into the membrane fast as the concentration is high,
27
Saturation point
Facilitated diffusion, we have saturation mechanism, rate/speed of entrace of molecules is inversely proportional to the concentration, because trasporter are a defined number so they can only take that number of molecules per time
28
Ions channels
nervous system importance
there are channels that are always open, passive channels
channesl that open and closes depending on the stimuli.
only one type of ion can pass at a time through a channel.
we have 3 types of ion channels.
1. Potential controll: change in voltage
2. Ligand controll: interaction with ligands such as hormones, neutrasmetters. (chloride channel malfunctions: lungs- accumulation of sodium and chloride-cystic fibrosis)
3. mechanical stimuli: conformational changes
29
what have channels at the end?
They have a globulas structure called channel valve , when the channel is closed the valve is inserted so passage cannot occur
30
Active Transport
against electrochemical gradient, it needs energy through ATP hydolysis thanks to ATPase enzyme
31
Sodium/Potassium pump
Integrated type of transmembrane protein that has domains to recognise Na and K.
need ATP hydrolysis, to maintain the equilibrium( more K inside than outside, more Na outside than inside). The transporter is the ATPase.
The concentration changes due to passive diffusion.
Steps of the pump:
1. Open inside cytoplasm, 3 ions sodium enter. activate te ATP hydrolyses, ADP we have
2. Phospate added to the pump, inner side of pumpo, conformational change,
3. close on cytoplasm, open outside , release of the 3 sodium, change conformation, potassium recognization
4. 2 K inside, traslocate to initial position, K goes in the cytoplasm
5. for traslocate, Phosphate is deleted, conformational change
6. relase K in the cytoplasm, all over again
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Exocytosys
enter/exit material inside the cell. Active diffusion.
| relase things outiside , secrete material, into bloodstream, specific receptors., answer
33
Phagocytosis
cell eating, digest molecules.
Bacteria go inside like this
1. receptor recognize the bacteria
2. Bacteria binds to with cytoplasm through phagocytosis
3. bacteria is digested
34
Endocytosis
Internalisation of substances.
1. Fluid Pinocytosis: liquids
2. Receptors -mediated endocytosis: thanks to cellular receptors
3. Macropinocytosis_ like phagocytosis
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Receptors mediated endocytosis
membrane receptors, mutual reconition between receptor and ligand, receptor is charged by solute/ligand, vesicle, endocytosis, diffuse inside the cell
Cholesterol LDL uptake
36
Cells ...
sense and send information, answer to changes in the enviroment
37
Cell receptors
transmembrane proteins that brings extracellular messages into the cytoplasm through plasma membrane receptors (Proteic type of ligands) or in the nucleous through nuclear receptors (lipids/steroids ligands)
38
receptors
can be
1. On membrane, proteic signals, binding membrane , responseinside the cell
2. In cytoplasm, steroids hormones, lipidic signals , traslocation from cytoplasm to nucleous , transcription fractor, activate transcription
39
Cell Comunications
comunication based on chemical signals and receptors.
| transduction pathways: from the signals that intereact with teh receptor provoking an answer
40
Types of signals
- Local signaling: short distance, affect cell producing them or nearby by diffusion . Paracrine : first cell produce the signals, Autocrine: cell both source and receiver, Intacrine: signals do not leave the cell
- Hormonal signalin: endocrine, long distance, blood stream to distriubuition, only cells with the receptors for the hormon signals will bind it and produce a response.
41
Gap Junction
a signal may pass through the gap junction from one cell to another, importanto for synchronize response on tissue, signal pass very fast to first to last, answer happens at the same time
42
Neurotrasmitters
neurotrasmitter ligands, relesed in the bloodstream, receptor, response
Neurons may give rise to a local type of action, neurotrasmitter is released into the synaptic bottons
43
Signal transduction stages
1. Receptions: ligand - receptor
2. Transduction: structural change in receptors, signals goes inside
3. Cellular response: cytoplasmic receptors produce a response
4. Termination of response: ligand leave the receptor
44
Types of Ligands
3 types of ligands.
1. Endogenous compounds : originates in human body
2. Drugs: 2 type based on the function after binding the receptor
- Agonist: similar response of the endogenous ligand . Partial antagonist, produce a non complete effect, used when the endogenous compounds is still present in the body but in a low concentration
-Antagonist: do not produce a response
45
Types of Receptors
- on plasma membrane: lipophobic ligand
| - on cytoplasm/nucleous: lipophilic ligand
46
Types of plasma membrane receptors
1. Ion channels
2. Tyrosine kinase receptors
3. G-protein linked receptors
47
Ion channel receptor
They open/close for ions to enter/exit the membrane
| stimulated by light, electric charge, chemicals
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types of domains for receptors
1. Extracellular domain: sugars or carbohydrates attached to the proteins
2. Transmembrane domain: pass through the hydrophobic part of the plasma membrane. this domain, responds to the binding between the ligad and receptro in the extracellular domain, with a confomational change that activate the cytoplasmic domain
3. cytoplasmic domain: produce response inside the cell
49
Rceptor Tyrosine Kinase(RTK)
Kinase activity; the receptor attach specific phosphate to tyrosine.
crucial to control important biological responses.
Receptors acts in couple, for be activated, dimerize, some need 2 ligands, others only one
50
Direct Pathway
the receptor make the phosporylation.
1. recognize ligand
2. conformational change or the receptor by trasmembrane domain
3. activation of cytoplasmic domain, response inside the cell, cytoplasmic receptor site, protein kinase in cytoplasm
4. cytoplasmic domain of receptor, response, autophosphorilation
51
Indirect Pathway
Indirect because it will activate other factors, produce a cellular response inside the cell. The cytoplasmic domain do not have the ability to autophosphorilate.
Phospates will produce binding sites for proteins with SH2 domains, called adapter proteins, like GRB2( has inactive GRF (guanine releasing factor) connected to it.)
1. GRB2 binds SH2 domain(receptor complex) activate GRF
2. GRF activation + GTP, activate RAS protein (inner surface of plasma membrane anchored by a prenylic group bound to lateral chain of cysteine)
52
RAS protein
monomeric G protein.
GTP= active
GDP= Inactive
GRF replace GDP with GTP, GTAapse activity
1. Activated RAS activate the first cascade proteins RAF(MAPKKK-MAP kinases kinases kinases) first process kinase
2. RAF phosphorylates another cellular kinase, MEK(MAP KK)
3. MEK activation, phophorylation of MAPK, activation
this is the kinase cascade, end in a signal
the last MAPK produce activation of DNA with changes in gene trancription.
RTK:
1. signal through plasma membrane
2. external domain of receptor with ligand regulates the enzymatic activity pf cytoplasmic domain
3. tyrosine phosphorilation of cytoplasmic signaling that involvese 2 pathaways
53
Transduction in a ion channel
1. Activation of ion channel change the membrane permeability, creation of eletrical signal
2. Cl, Na, K go through different pumps, create an electical potential of the membrane, that change when the signal pathway is active in order to produce an electrical response.
3. The change of electrical potential/voltage, will produce the cellular response(nerves brings signals to brain). the signal involves increasing or decreasing some kind of protein function
54
Transduction
All the process inside the cell work because of the phosphorylation and dephosphorylation of the protein is the key to permit it to act or to inhibit some kind of process inside the cells.
55
Protein kinase cascade
it's a domino effect, at each step we have the activatio of a protein kinase. Each kinase can catalyse multiple phosphorylations at their target point.
1. RAS is activated
2. RAS will activate RAF(MAPKKK)
3. RAF cause phosphorylation and activation of Mek1 (MAPKK)
4. Mek1 phodphorylate and activate the tird kinse succession, Erk1
5. Phosphorylation of Erk1 activate it, migrate to nucleus
6. in the nucleus the Erk1 phosphorylate the "myc" transcription factor, and activates the gene for this pathway
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G-protein coupled receptors
cell surface receptors that do not possess a tyrosine kinase activity, but are membrane glycoproteins that produce the transduction of signals between the extracellular domain and intracellurlar one.
this proteins have 3 domains:
1. extracellular domain: recognize the ligands, carbohydrates on surface
2. intracellular domain:
3. Transmembrane domain: crosses the membrane multiple time (g-proteins that will posses 7 alpha helical domain) . After a specific message is bind with the extracellular domain, this domain will change its conformation , this activate the third domain, the one inside the cytoplasm, it create a response.
The first messenger(ligand) will bind to receptor , that will activate an effector.
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The effector activated by the first messenger binding with the receptor, how many pathaways can follow?
2 pathways
1. through the effector Adenylys Cyclase, that is an enzyme that produce cAMP sarting from ATP.
2. Through the enzyme Phospholipase C that will produce two secondary messenger:
1. InsP3(Inositol Triphosphate) a sugar
2. DAG (diacylglycerol)
The G-proteins involved in this, are trimeric, have 3 subunits(alpha, beta, gamma)
1.FIrst messenger binds to the external side of the receptor, the trasnmembrane domain change its confomation
2.activating the cytoplasmic domain that will activate the trimeric G-proteins.
because, Beta and Gamma subunits separate, leaving alone Alpha that finally becames active. The alpha activation cause the effector of Adenylyl Cyclase or Phospholipase C to activate.
we have at the end an amplification effects, we have a lot of molecules as secondary message
58
Small molecules and Ions as Second Messengers
The end of the effector pathways, both gives small molecules and ions as second messengers,that are water soluble, small, non protein and pass through diffusion.
Cyclic AMP and Ca ions are common secondary messengers (PIP3 and DAG)
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types of G-Proteins
1. Monomeric : RAS, Rho ecc...
2. Heterotrimetic : 3 subunits, only alpha bind to GDP and GTP, with GDP is inactive(when is with beta and gamma), with GTP is active(when is alone)
G-proteins with the two enzymes, kinase(phosphorylation) and phosphatase(dephosphorylation), are the two switches of the system.
they controll:
- synthesis of protein
- intercellular traffic
- exocytosis
- endocytosis
- cell division/differentiation
Human genome has;
- 20 genes for alpha subunits
- 5 genes for the beta subunits
- 6 genes for gamma subunits
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Subunits of G-proteins
Three sub units:
Galpha: carries the binding site for nucleotide, at least 20 kinds are known
Gbeta e Ggamma
1. Galpha at inactive state has GDP, in its binding site, ligands binds with the associated GPCR, an allosteric changes in the receptor occurs.
2. another allosteric change take place in Galpha, GDP leave and is replaced by GTP
3. GTP activate Galpha
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Types of Alpha Subunits
Ga S; stimulatory adenylyl cyclase, associated with: adrenaline, glucagon, LH(luteinizing hormone), PTH(Parathyroid hormone), ACTH(adrenocorticotrophic hormone)
Ga Q: activate the Phospholipase C(PLC) that generate as seconds messanger; inositol triphosphate(IP3). Vasopressin, TSH(tyroid stimulating hormone), angiotensin
Ga I: inhibitory, adenylyl cyclese lowering the level of cAMP in the cell
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Toxins of G proteins
Cholera: Modification of G alpha S, inhibits GTP hydrolysis, increase cAMP in the epithelial cells of intestines, Cl- channel phosphorylation mediated by PKA, increase electrolytesy and H2O, diarrhoea
Pertussis: G alpha I modification, inibits Adenylate cyclase, PLAC2, PLC and K channels, lignd-R are decoupled
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ATP to cAMP conversion
1. Hydrolysys of ATP into ADP
2. hydrolysys of ADP into AMP
3. water molecule released by AMP, dehydratation, ATP to cAMP
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Cyclic AMP Pathways
1. first messenger and receptor binds on the extracellular sites
2. conformational change in transmembrane domain, activate the cytoplasmic site
3. Cytoplasmic site produce G alpha subunits, bind GTP
4. The active G alpha, work as effector on adenylyl cyclase
5. Adenylyl cyclase will produce cAMP (ester reaction between acid P group and -OH alcohol)
6. cAMP recognize the specific protein Protein kinase A (PKA)
7. Phosphorylation of target cellular proteins
Thanks to the ability of PKA to interact with different target cellular proteins , we will have several kinds of response.
through this way we can have response by using Adrenaline, ACTH, Glucagon,LH, Acetylcholine, Parathyroid Has first messengers
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Second Pathway: Hydrolysys of PIP2
the second kind of effector, Phospholipase C has to be activated
Inserted into the plasma membrane there is enocytol diphosphate (phospholids, glycerol bond with 2 ester bonds the tails and 1 to phosphate)
The phospholipid binds the phosphate group with a sugar called inositol diphosphate, hexagonal that has 2 more phosphate groups.
this pathways is based on a second messenger derived from the glycophospholipids, PIP2
The Phosholipase C will work only on that kind of phospholipids. It cuts the bond between the inosytol and phospholips, and we have two kinds of secondary messanger.
DAG(diglyceride, glycerol + 2 fatty acids 2 ester bonds and OH group)
InsP3: inositol triphosphate, inosytol diphosphate with th epolar head of phospholipd.
1. Hormone interact with receptor, conformational change of transmembrane domain, activation of G proteins. Gaplha Q became active when binds the GTP and interact with Phospholipase C.
2. separation of phospholipis on the plasma membrane, that is phosphatidyinstinol
3.phosphatidynstinol divided in 2 secondary messengers, DAG(reains on plasma membrane intercat with protein kinases)
and InsP3
4. the traget protein of this pathways is the protein kinases C(PKC), interact with secondary messenger , DAG, reach PKC and insitol1,4,5 triphosphate, a sugar that can reach the endoplasmatic reticulum, where there is Ca ions in high concentration. used during fertilization, the acrosomal reaction between the egg and the sperm happend because of the Ca reacting with the egg, creatin a fertilization membrane, blocking sperm, to avoid plyspermia.
5. InsP3, reach the reticulum, causing the release of Ca
InsP3, DAG and Ca, all together are the thrid secondary message
Ca and DAG react with PKC, that cause phosphorylation of other cell proteins.
To transportate Ca that act as a secondary message in the reticulum we need ATP, ER has a Ca pump that always works to use Ca as needed
but release of Ca by InsP3 is passive diffusion
PKC may link two pathways (RAF and PCK) , it can be activated by Ca and DAG producing many responses.
Cells are full of networks , arise from interaction in which a component of a pathway can regulate the activity of another patway
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nuclear cytoplasmic kind of receptors and transduction
this receptors will answer only to steroid hormones, that will pass the plasma membrane directly thanks to the fact that they are lipidic. The hormone plus they specific receptor will go to the nucleus to start the transcription of specific genes related with that signal. Steroids hormone are transcription known for sex differentiation and sexual dimorphism
67
Why are the receptors in stanby inside the cytoplasm waiting for specific hormone that will interact with themselves producing responses inside the cell and ultimately transcription of the specific genes?
Because steroid interacts with some kind of Heat Shock Protein(HSP) that will block the receptor in the cytoplasm . All steroids receptor will interact specifically with hsp90.
Hsp90 mask the DNA binding site of steroids receptors until specific hormones arrive into the cell.
There is steroids receptors with a domain that will recognise the specific sites on the DNA, that will interact with the steroid receptor to produce a response via the transcription of specific genes. If the receptor is blocked by hsp90 it can't recognise the DNA. Hsp90 will block the receptor untili the specific hormone arrives at the location of the receptor
E.G
estrogen interacts with hsp90 and is blocked in the site of recognition of DNA and two other hsp will maintain the receptor in stanby in the cytoplasm.
When estrogen arrives in cytoplasm, it will interact with two estrogen receptors, cause this two will be dimerized after the interaction with specific hormone.
So, the action of estrogen, not only permit to leave each hsp90, hsp50 and hsp70 by the receptor, but also the dimerizetion of the estrogens receptors.
the receptors that are free from hsp, will move inside the nucleus and recognize specific area in promoter region before the TATA-box. It will interact with the DNA producing the activation of the genes that are regulating the estrogens.
68
What are nuclear receptors?
Specific superfamily formed by structurally related ligands that are inducible transcription factors, like: steroid receptors, thyroid/retinoids receptors, Vitamin D receptors, orphan receptors for which no ligand has been yet identified.
While having in common a modular structure, they are active by distinct lipophilic small molecules, particulary steroids hormones know as glucocorticoids (progesterone, estrogen, testosterone, retinoids, fatty acids derivatives), they are nuclear receptors that are in stanby inside the cytoplasm
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what is a gene?
a tract of DNA that contains the information to produce either a specific protein or a specific rRNA, tRNA, or other untranslated RNA
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The three specific nucleotide sequence to constiture a functional chromosome
1. Origin of replication
2. Centromere, to attach to the spindles during the division
3. Telomere, to preserve quantity of the DNA
Telomeres are present in the extremeties of chromosomes in germ cell, because it needs to have all the information necessary to pass to the daughter cell before fertilisation.
ONLY SOMATIC CELLs can lose DNA information from their extremeties, cause it's important for their deletion, because it indicates that the cell is too old and it needs to undergo apoptosis.
It is not good for germ cells, as all genetic material must be preserved.
Telomerase enzyme, produce universal transcription usign RNA template to produce DNA.
sister chromatids are isogenic= one is the copy of the other.
The centromere possesses a proteins, Kinetochore that will produce the separation of the two sister chromatids during mitosis and meiosis
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Development and chromosomes
- Difference in chromosome are associated with difference in the way we grow.
- karyotypes of male and females are not the same. Females have two large X, males X and Y. sex chromosomes
- Unsual growth is associated with chromosome abnormalities (Down Syndrome, trisomy 21)
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Chromosomes and reproduction
- Come in pairs: maternal and paternal
| - sex cells have halved the number of chromosomes (aploid) one of each is taken.
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Meiosis
- cell division to make sex cells
- Meiosis halves the number of chromosomes from each pair at random and places them in a sex cell, enormous variations thanks to recombination.
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Cell theory
All cells come from pre-existing cells.
- Living from non living is the capacity to reproduce themselves
- cell reproduction allows the continuity of life, growth, and repair.
- cellular reproduction can be asexual or vegetative or sexual
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Cell cycle
Most of cell cycle takes place during the interphase(sum of G1, S, G2). cells that do not undergo divition do not present a cycle
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the three categories of cells
1. Highly specialised cells that have lost the ability to divide, perennial cells (nerves, muscle, red blood)
2. Differentiated cells that do not normally divide, stable cells that divide only in response to stimuli
3. Active proliferating cells, labile cells(stem cells in the epithelial tissue and bone marrow cells and germ cells)
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Stem cells
stem cells are cells that produce the specific cells of the tissue in which they are.
the only stem cells that are capable of becoming any type of tissue is the present in fetus, at beginning of its development, called blatomeres. At first phases of development the cells divide and give rise to particular tissue and the differentiation starts at that moment.
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G0 phase
cells that are in stanby, waiting for a signal such as growth factor or mitotic agent. We also find cells that cannot return in the cell cycle.
GAS, Growth arrest specific genes, block the cell in the stand by point. If there is a mutation of these genes , the cell will enter the cell cycle , causing division. if the mutation is harsh, the cell will continuisly divide and cause cancer(majority)
helthy GAS are oncosuppressor
```
G1 last from 6 to 12 hours,
S 6 to 8
G2 3 to 4
M 1 hour
a total of 16 to 25 hours,
Meiosis takes longer than mitosis, because in mitotis DNA doesn't need to be checked.
```
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The cell cycle control system
the sequential events of the cell cycle are directed by a dinstinct cell cycle control system.
it has specific check point, where the cycle stop and it can't start again until the check point doesn't give the go-ahead signal.
END of G1: check DNA to ensure perfect replication
END of G2: cell has done replication and G2, the cell need to go in cell division, so this check if the DNA is well replicated
DURING M PHASE: if each one of the chromosomes have been correctly attached to the tubulin filaments on the spindle., if not, cell division cannot propely occur
the transition from G1 to S phase is controlled by the first check point that is also called restriction point; this point will control that all the molecules needed for the DNA replication in the next phase (S) are just well preparate.
Only if everything is ok the cell may pass the restriction point.
Another check point is needed between the transition G2-M that will control the quanlitative or quantitative of DNA replication and if the cell possesses all the material that is needed to prepare the mitotic spindle, this means that during the G2
gap the cell must produce all the tubulin that will be used to produce the mitotic spindle in order to proceed with the nuclear and cellular division.
The third and last one is the point of exit from the M phase that will control if every chromosome has been attached correctly to the spindle during the mitosis or meiosis.
Mitogen: molecule than ennance the cell to begin divison or the rate at which it happens. when we add it, there is only transcription of early genes that in turn will later produce the delayed response genes: cyclins or transcription factor needed for cellular cycle
Myc transcripition factor. It is a potent regulator of cell proliferation. Excessive levels of myc leads to tumors.
G1 and G2 gives the cell the time necessary for the correct cell mass growth and duplication of orgnanelles, if this not happens, the cell will be smaller each cycle that undergo.
Standards cell: G1 S G2 M, G1 S G2 M
Embryonic cells: S M S M S M S M S M S M
there is no gap before DNA synthesis and cell division. The first zygote division, produce blastomeres(big) that will continue to divide in the same volume and space until a certain ratio between the nucleus and cytoplasm occur. This is the segmentation process, after it, we have mitosis with production of standard cells.
ZYGOTE --> BLASTOMERES --> SEGMENTATION--> MITOSIS
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Density dependant inhibition and anchorage dependance
Cells will stop if the completely cover a surface, so the density dependant inhibition stops the growth, if cells are removed density decrease and cell will divide for cover the area from which cells are taken.
anchorage dependance: cells must be atached to a substratum to duplicate
it is important for normal cells, the blocking of cell growth, due to GAS genes, is able to block cell division where is not needed
In cancer cells neither of this two inhibitors works.
Multylayers of cancer cells form until they reach a medium, that has everything needed for the cell to return the cell cycle.
Loss of cell cycle controll in cancer is due to the loss of normal response of the cells to the controls mechanisms.
Cencer cell may not need growth factors to grow and divide
-they make their own growth factor
-they convey a growth factor's signal without a presence of a growth factor itself
-abnormal cell cycle control
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How do cells know when to divide?
There are communication signals:
-dead signal coming from a cell, that specific cell is going to be delated through apoptosis, when the apoptosis happens a neighbor cell will receive this signal and in order to fill the empty space left by the apoptotic cell it will start to divide.
Communication signal is very important because it makes replacing cells possible.
chemical signals in cytoplasm can give cue or signals that are usually proteins like activators or inhibitors.
Other very important signals are the “Go-ahead” signals:
● Protein signals that promote cell growth and division:
- Internal signals that are called promoting factors
- External signals that are growth factors or mitotic factors
● Primary mechanism of control that is due to the phosphorylation, that is mediated by an enzyme kinase, which can either activate of inactivate cell signals.
additions of growth factor make the cell goes from G0 to G1
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Growth factors
The growth factors may be also indicated as the proteins that stimulate cell growth and division, they act through interaction with specific receptors on the plasma membrane and then only act on the target cells; they will go to the specific cell through two different ways:
1) Paracrine: a signaling cell will send the signal directly to the target cells
2) Endocrine: an endocrine cell will reverse directly in the blood stream its hormone that will reach the specific target cells all over the body to activate the cell division.
The growth factors can induce the quiescent cells (in the G0 Phase) to divide.
Example of growth factor
● Platelet derived growth factor (PDGF)
- made by platelets in blood clots
- binding of PDGF to cell receptors stimulates cell division in connective tissue
Only a small but crucial part of the cell cycle is regulated by mitogens.
Cultured cells deprived of serum or growth factors come into quiescence (G0),this means that this cells will activate GAS genes (oncosuppressor genes) that will leave the cell in stand-by outside the cell cycle.
Mitogens promote the exit from G0, and the cell will complete the cycle if the mitogens remain present until the restriction point (mitogens are needed from the cell to permit the passage of the restriction point). After the check point most cells “will cycle”
even in the absence of mitogens.
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controls, sensors, and repairers of DNA damage
checkpoints/controls: ensure that the cell is competent, able to pass to the next stage of the cell cycle; otherwise, the
cell is going to remain in the previous stage until she produced all the component needed to go ahead.
OVERVIEW of the CELL CYCLE CONTROL
There are several factors that regulate the cell cycle assure that cell divisions happens correctly.
Two irreversible points in cell cycle:
- replication of genetic material, before a cell divides, the DNA is checked to make sure it has replicated correctly. If DNA does not copy itself correctly a gene mutation occurs.
- separation of sister chromatids:if the sister chromatids that are produced after the replication of the DNA are not well divided we will have damage inside the cell.
Checkpoints
- process is assessed and possibly halted; the cell cycle is controlled by STOP and GO chemical signals at critical point (G1, G2 and M), that indicate if the cellular processes have been completed correctly.
For many cells, the G1 checkpoint seems to be the most important one.
If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2 and M phases and divide. If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing stage called G0 phase.
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checkpoints in cell cyle
1. G1 ----> S. start/resctriction point. Can DNA synthesis begin? there are 2 oncosuppressor:
-retinoblastoma protein: needed to pass rescrition point
-P53 "Guardian of Genome", acquire information about the DNA synthesis. it's the one who decide if the DNA synthesis can happen. this proteins prevent any possible mutations that can occur, are important to avoid cancer
if the cell recives the Go signal, it will divide in:
-external signal: growth factors
-internal signal: cell size and nutrition
2. G2---> M : check if the dna synthesis been completed correctly, commitmento to mitosis
3. Spindle Checkpoint: Check if all chromosome are being correctly attached to the spindle, if sister cromatids can be correctly separated
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Cell cycle clock: cyclins and Cyclin-Dependent kinases (CDKs)
Cyclins are the regulatory part of CDK, CDKs have the catalytic activity. CDK add phosphate group to the proteins to their activation.
involved in cell cycle.
Dimer that mediate the transiction between G2 and M is MPF(maturation promoting factor), it'a a cyclin-CDK complex that trigger that transition.
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Growth factors and Cancer
Growth factors, Proto-oncogens(mutantions can turn them into oncogens) and tumor suppressor genes, can cause cancer.
Tumor spuppressor genes, that inhibits cell division can be switched off, and cancer will grow without beign stopped
e.g. P53 and retinoblastoma proteins, will miss the mutated genoma and make the cell continue the cycle.
damaged cell are more likely to undergo more mutations.
7 or more mutations= Cancer, that needs to happens in the right place and time
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P53
- stimulating repair enxymes for the DNA
- Force the cell in G0
- Keep cell in G1 arrest
- apoptosis of damaged cell.
ALL cancer shut down P53 activity.
we test his activity with UV damage. P53 should sense the damage, if it is big, cell must undergo apoptosis(P53 stimulate transcription of BAX genes, that are apoptotic) if is small, it will be blocked until the repair occurs
P21CDK inihibitor, inhibits the cyclin CDK , and pause the cycle, if damage is repaired, the inhibitor stops and cell will continu the cycle.
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Cell cycle is regulated at molecular level
experiments suggest that cell cycle is driven by chemicals signals present in the cytoplasm.
Masui ans Market's experiment, led to the discovery of cyclins and CDK.
-frog oocytes in dormanr G2
-Progesterone makes the cell go in M by affecting triggers
-3 groups of donor oocytes: Progesterone 2 h. progesterone 12 h, no progesterone.
- injected cytoplasm 12h progesterone into another oocyte arrested in G2, this cell complete the cycle. Relized that there was a factor causing it, MPF (Maturation, Promoting Factor, mitotic cyclin and cyclin-dependent kinase)
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Evidence for cytoplasmic signals
experiments( 2 cells from different phases fused together in a two nuclei cell) suggest particular chemicals control to the progression of phases. Cell division is controlled by a set of molecules in the cells(Two cell fused , one in M phase, the other nucleus start also Mitosis)
this experiment, made MPF and SPF taht encode for Protein Kinase, identify.
Cyclins are periodic proteins that are rapidly degraded, because they work only in a certain places in the cell.
Dimer of MPF produces, it helps the transition from G2 to M. Cyclins and CDK are important.
The complex formed by CDK1 and Cyclin B will produce phosphorylation of some protein. breakdown of tge molecular membrane, cytoskeleton reorganization, chromosome condensation prior to mitosis. , this activity is full when M.cyclin is at its highet level.
Cyclin is low at interphase, but it rise it's concenration during mitosis. Mcdk, low during interphase, hight in mitosis.
6 Cyclins known (A-F), 5 CDK (1.5)
CDK activated by cyclines are serine-threonine kinase proteins.
they phosphorylates:
-substrates in the various stage of cycle, G1 and S, histones, so compaction of chromosome is allowed
-nuclear lamina, break of nuclear envelope
-cytoskeletal proteins
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Tumor suppressor genes: genes that control the cell proliferation.
2 oncosuppressor: P53, retinoblastoma protein.
P53, act twice, at G1-S and at G2-M.
retinoblastoma protein: G1-S ,restriction point, block) the production of gene that will take DNA replication to next step mutation of this protein cause cancer know as retinoblastoma(high incidence).
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Cancer
disorder in whitch some of the body cells lose the ability to control growth.
If some cancer cells breaks from a tumor and spread through the body through bloodstream , they can form "metastasis", that is the secondary step of the tumor that will produce progression of it until the death of people with this kind of cancer.
if cells remains in the original site we have a benign tumor
cancer develops after at least 6 mutations , a normal cell has low probability to undergo mutation, but if a cell already has one, it will be more easy to produce more.
sensibility of a cell to mutations is its number of mutations. After 6 cell can grow into a cancer cell and ignore checkpoints.
If the cell is controlled by P53 it can be repaired or killed, but if it is not, the cell will increase size and the first cell that possesses the first mutation will be target for the second. and the one with the secondi will be target fot the third, cell undergo uncrontrolled growth
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Cancer: new "miracle drugs"
There are dru used against cancer, but they are too generic, because they stop cellular division, but if we stop cellular division we can stop also the normal cell division. So we have drugs that act on specific cancer cell
1- Gleevec, target protein (enzymes) only found in cells. Chronic myeloid leukimia is the one in which there is the presence of the Philadelphia chromosome, that is a karyotype, in which the chromosome couple number 22, is different, is smaller.
Before the drug, people died after 5 years after the diagnosis.
Chromosome 9 has a gene promotor of cell cycle, "abl gene", also 22 have it, "bcr gene", so they promote transitions during cellular cycle.
in Philadelphia chromosome we have a traslocation between 9 and 22.
Philadelphia have a new gene called "chimeric gene" that has abl and bcr gene, abl is inserted into bcr. This altered fused abl gene cause leukemia.
the protein Brc-abl, the chimeric, cause neoplastic transformation, on the center there is a site activated by ATP and will produce the attahcment to substrate producing the disease.
When researcher understood that the key was the ATP, they produce Gleevec, that target cells only carrying the molecular anomaly. It acts as an antagonist of ATP. When people with the chronic myeloid leukimia are given gleevec, it will insert into the brc-abl protein, recognising the domani that normaly recognise ATP and his antagonistic action block the protein, because the protein will not recognise the substrate and won't act, blocking leukimia.
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Viruses what they are ?living or non living?
Viruses are both alive and non living, they have properties of both types. They can be killed, but also crystalized, they can't maintain homeostasis.
Viruses are non cellular particles made up of genetic material, DNA or RNA, not both, and protein that can invade other cells.
We have 2 types of Viruses:
1- DNA viruses: easier for them to invade our cells, since we also have DNA, It can bind with the host DNA and use it to produce the viruse's protein
2- RNA
Stanley, cystalized sap from tabacco plant(Tabacco mosaic virus) and observed that viruses where made of nucleic acid and proteins(proteic capsule). Some viruses can also be covered in a capsule which is made by a membrane
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Smallpox
- Edward Jenner elaborate the smallpox vaccine using milder cowpox virus
- Deadly viruses are virulent
- Smallpox has been eradicated thanks to Jenner vaccine but it is coming back
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Viewing and size of viruses
-Viruses are smaller than the smallest cell, misured in nanometres cannot be seen until the electron microscope invention.
Polio virus is one of the smallest, 30 nanometres, smaller than E.Coli
Viruses can expand quickly thanks to their small size
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Viral structure
Characteristics:
- non living structures
- non cellular
- protein coat called capsid
- nucleic acid core, DNA or RNA
- can reproduct only if they are inside an host cell, become living only after invading a cell
Virus dogma: Viruses cannot repoduce outside an host cell also because they don't have the metabolism for the repdoruction.
So, when they enter inside a cell they will acquire the metabolism and other things that are specific to the cell, blocking the specificity of the cell, promoting only what they need.
Use metabolic pathways to produce its proteins and its specific genetic materia. So the host cell will just produce the protein needed for the daughter viruses capsid.
Then they use the mechanism of DNA reproduction to replicate its specific DNA that must be located inside the capsid
-Some viruses might have a protective envelope around them(more dangerous)
-Some can have specific spikes to attack the host cell (coronavirus)
-Most viruses infect only specific type of cells, due to specific recognition between spikes and receptors on the host cell, this
facilitate the viruses's penetration inside a cell.
-Viruses are cellular or species specific
-Viruses have capsid, that are each made of individual protein subunits: CAPSOMERS
-Ability to cause disease: smallpox, measles, mononucleosis, influenza, colds, warts, AIDS, ebola, COVID, SARS-MERS. Others can cause cancer, like leukemia
-Viruses free cells are rare
Viruses are inactive outside the cell because the viruses lack ribosomes and enzymes needed for the metabolism , cannot undergo protein biosyntesis. They will use raw material and enzymes of host cell to reproduce.
Ebola and HIV, are important.
HIV produces AIDS, drugs now prevents the spread of the virus in infected people, so virus cannot reproduce inside an infected person.
If HIV positive stops taking medicine, AIDS will spread.
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Virus shape
- Helical shape like ebola
- polyhedral like influenza: capsomere is polyhedral and the single capsomere will produce the capsid that is the proteic envelope/coat of the virus, where there is a nucleic acid inside.
-Bacteriophages, most complex ones: they posses other kinds of structures, like tails fibers, base plate that may protude inside the membrane of the bacteria.
It use base plate, pin and tail fibers to attach to the membrane of the bacteria and produce enzyme to eliminate the bacteria's membrane, so the DNA can move from the capsid to the bacteris
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herpes and other viruses
-Herpes virus is not dangerous and can have 2 forms:
1. Herpes Simplex 1
2.Herpes Simplex 2
Has a specific target in mouth, it will increase its replication when there is a disease, a fever or when travel long distance.
- Adenovirus: common cold
- Influenza virus
- Papillomavirus
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Virus identification
Parametres:
- RNA or DNA viruses
- DO or NOT have an envelope (external than capsid)
- Capsid shape
- the host they infect
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Bacteriophages
They attack bacteria, because of their particular characteristic, they have an head made by coats, that is the capsid, made from capsomers(monomeric protein) and inside the head there is genetic material, DNA. They also have a neck, a collar, a sheat, base plate and tail fibers.
Phages of T-line(inject directly the material) have, icosahedral heads, double strands of DNA and tails. Land in lunar module and attack the bacteria directly, injectig their genetic material in the bacteria. (most common are T4 and T7)
T.phages attack mainly the E.Coli.
T-even bacteriophages have the head made by 20 triangular surfaces, the capsid contains the DNA and both head and tail fibers are made by proteins.
So bacteriophages are made just by 2 kinds of macromolecules:
- Proteins:head, tail. fibers
- Genetic material in the head.
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Coronavirus 19
Coronaviruses are large family of viruses that cause illnesses in animals and humans. One coronavirus that infected bats mutated and became able to infect humans.
Human coronavirus can cause, mild illnesses like cold.
SARS: Severe acute respiratory syndrome, is an illnesses caused by SARS-associated coronavirus (SARS-CoV)
Previous coronaviruses included SARS-CoV and MERS-CoV
SARS-CoV2 is the new type of corona virus.
Probabily corona virus mutated by a jump of species, from bats to humans, maybe with another intermediate animal, probabily camel.
Coronavirus attach to the respiratory cells thanks to the proteins on it's external membrane, "spike", that recognise the receptor on the host cell.
1. Recognition between spike and host cell
2. internalization of virus by endocytosis.
Here we can have antibodies that could stop the spread of virus, or not.
3. Endocytotic membrane will be lost and the virus will emit its specific genetic material outside in the cytoplasm.
Spike proteins of Coronavirus are just glycoproteins, they posses a recognition domain that is just sugar, the recognition is mediated by the sugar.
The receptor of host cells are ACE RECEPTOR.
Specific ability of viruses is to mutate their genetic material when infect host cells. After being infected a cell is forced to stop it's normal methabolism and produce the proteins necessary to make the virus capsid and the virus surface proteins.
The only possibility to prevent virus from mutating is to prevent infection through vaccines. Omicron is more infectius but less dangerous.
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Lytic cycle
Viruses can cause lytic cycle.
1. Attach to cell after the recognition of the receptor
2. Penetration (injection) of viral RNA (5 minutes)
3. replication due to synthesis of proteins and nucleic acids. (20 minutes)
4. assembly (maturation) of the new virus, proteins of capsomeres, capsomeres produce capsid, nucleic acid inserted into each capsides.
5. Assembly is completed, release of new virus in the enviroment and lysis od cell, so, cell will explode (go boom) releasing all the viruses in the enviroment, ready to infect other cells. (25 minutes)
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Retrovirus
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NOT RNA VIRUSES, they are different.
characteristic:
-made of RNA
-belong to retrovirus family
- have the enzyme reverse transcriptase, similar to transcriptase.
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When invading an host, with RNA also reverse transcriptase in injected.
The enzyme is able to convert RNA into DNA, and its used by the host cell to replicate the virus (capsid and envelope).
Reverse trasncriptase sythesized complementasy DNA molecules, cDNA, using RNA of the virus as a template for DNA.
HIV is a retrovirus.
Protein for HIV are been identified, expecially gp120 and gp41 (glycoproteins) , that mediate between human immune system and virus.
These proteins are the link by which RNA and reverse transcriptase enters the cell.
also the feline leukemia virus is a retrovirus
Drugs that act on reverse transcriptase are being made. A enzyme i the drug is capabeìle of blocking the reverse transcriptase, block the abitility of making transcription of the viral DNA into DNA.
Others blocks gp120 and gp41 to recognise the cell membrane, it block the synthesis of this proteins, it's like protease for these proteins, replicated viruses do not have those proteins so they do not have the capacity to bind to other cells inside the human immune system.
eukariotyck viruses have protective envelope
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Virus latency
latency: some viruses have the ability to become dormant inside the cell(like Herpes simplex) and it will be active only in certain times, otherwise it stay dormant.
Those viruses are latent. They will be inactive for long time but will be activated in response to some external signals.
Also HIV is a latent virus.
lysogenic cycle: inactivation of lytic cycle, will start after an external signal.
lytic cycle: immediate
lysogenic cycle: happens when we have an inactivation of the lysis, that cause latency
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Latency in Eukaryotes
Some virus will stay latent (e.g. nervous tissue)
.Chickenpox that cause Varicella.
-herpes
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Treatment of viral diseases
-Vaccines: many used the attenuated virus, that is less dangerous, that is used to produce an immune response and create immunity without causing the illness.
- Interfens: natural proteins made by the cell to fight viruses
- Antiviral drugs: such as AZT retrovirus, protease inhibitors that prevent capsid formation.
RNA vaccines: will introduce in our body the ability of our cells to produce specific proteins that will promote antibody response inside our cells. Increase the number of antibodies against the virus.
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Cytoplasmic membrane
all the cytoplasmic membranes are made of the same molecules.
Plasma membranes: phospholypids, proteins, cholesterol. proteins are inserted in it to give specificity (eukaryotic cells)
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Compartmentalisation
characteristic feature of eukaryotic cells, not present in prokaryotic cells. Enable eukaryotic organless to separe they specific content from the matrix and from others organels.
Each compartments is specifically working to produce a methabolic pathway, that is quite different in each compartment, is carrying out its own reactions, as a whole we have cell work
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Endoplasmatic Reticulum
Rough Endoplasmic Reticulum, RER: has ribosomes on it. has a cisternae shape, make protein products due to the presence of ribosomes, protein-secretory cells has a lot of RER.
Produce:
-Secretory proteins released by reticulum pathways
-Membrane proteins released by ribosome
Functions:
-Start of biosynthetic pathway
-protein syntesis
- syntesis of carbohydrates.
-Glycosylation of secretory proteins( membrane are not glycosylated), it happens twice.
1. in RER during synthesis, glycosylation co-transactional
2. cisterne of Golgi: post transactional.
This appens to help the correct folding of proteins, so the binding with chaperones proteins
Smooth Endoplasmic Reticulum,SER: tubular shape, proteins form RER go to SER to became lipoproteins.
Function: made lipids and cholesterol.
Will be present in steroid-producing cells(derived from cholesterol)
Steroids: androgens, progesterone, testosterone, estrogen.
Also abboundand in Hepatocytes, as they make lipids.
Males: lyding cells produce testosterone.
Female. follicular cells produce estrogens
SER in Hepatocytes:
-lipid synthesis(phospholipids, and cholesterol, fatty acids, steroid hormones (gonads and adrenal glans)
-Phosphatidylcholine: main phospholipid that is synthethized, catalyzed by Acyl-transferase
1- condensed fatty acid + glycerol monophospate
2- phosphatidic acid that react with a substrate for the next enzyes and so on
-Detoxyfication of organic molecule: enzyme Oxygenase, that transfer O2 to molecules, make them water soluble, removed by detoxyfication P450s., benzoalphapyrene(grilled meat) is harmless thanks to detoxyfication,is converted in a potent carcinogen.
- Ca++ sequestration Ca inside the cistern, regulated, promotes muscle contraction
- Methabolism of carbohydrates
Lipid bisyntheasis is assymetrical , single layers of plasma membrane is made of different kinds of phospholipids. in apoptosis, they got inverted. in SER there is rebalancing that happens with the help of flippase .
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Golgi apparatus
present between the plasma membrane and RER, final secretory product in golgi .
the intra-cellular compartments, constitute the membranous organells, this is of extreme biological importance, first step of change of cells from prok to euk.
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Secretory Pathways
There are 2 pathways through the proteins is trasported outside the cell.
1.Constitutive secretory pathway:
the secretory vesicles continuosly go to plasma membrane to be released outside of the cells, this happens without any signals. The vesicle produced by RER are finalized by Golg, move to plasma membrane and fuse with it to get out of cell.
- delivered via membrane vesicles from TGN to cell surface
- share same vesicles ad csp
- little is know how plasma membrane proteins are sorted into vesicle
- maybe more classes of carrier vesicles.
Vesicular Transport:
movement of molecules from donor to acceptor. Made by RER, to golgi for final packing.
Important for primary amino acids, secretary proteins, RER, membrane proteins, lysosomal, nuclear proteins have to be transported in this way.
Experiment of Jamieson and Palade: pancreatic tissue.
1. pancreatic cells in a flask with amino acids,for specif protein synthesis.
2. pancreatic cell in a separate flask with radioactive amino acids
3. 4 minutes later; cells are made of radioactive ones
4. the radioactive cells are putted in a normal amino acids flask.
5. final product is a mix of radioactive and normal proteins.
3 minutes: protein in RER
20 minutes: Golgi
2 hours: protein leave the cell
2. Regulated secretory Pathway
need a signal to move the vesicles to the plasma membrane, to fuse and get out.
If there is no signals the vesicle remains suspended in the matrix, signal is given when vesicles are needed into the cell.
The signal is an hormone or neurotransmitters, that binds to receptor on plasma membrane and transduces the signal to the secretory vesicles to fuse on the membrane.
This occurs un major cells of the body.
Insulin secretion:
1. insuline released after having lunch. Insuline is suspendend in matrix until they recive the signals to maintain glucose level in blood.
If there is more glucose in blood, pancreas will secrete insuline
if there is less glucose in blood, glucagon in secreted , to increase glucose by breaking glycogen. Those hormones are antagonist.
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lysogenic cycle
In lytic cycle, the new phage DNA and proteins are assembled into virions and are released after the lysis of the host cell.
Sometimes the genome of the virus and the one of the bacteria will fuse together, and stay like this for a long time, External factors cause this lysogentic cycle to perfom a lytic one and cell explode, dieing, releasing the virus.
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Phosphorylation and dephosphorylation
protein kinase= add a phosphate group, protein will be activate/blocked by this adding (phosphorylation)
protein phosphatase: remove a phosphate group (dephosphorylation) , same things, protein will be activated or blocked by this removal.
During the signal trasduction pathway, happens the phosphorylation.
1. Protein kinases transfer a phosphate group from the hydrolysis of ATP to a specific amino acid (serine)
2. We have phosphoserine.
on the contrary we have the enzyme phosphatase that will remove the the phosphate group.
This processes are parallel and antiparallel, at the same time and produce activation/block of proteins
