L15 Flashcards
what was believed about porteins before the 1940s
that we kept all of out proteins for our entire life’s but because of radioactive isotopes during the wars we learned that this was not the case
how do lysosomes break down proteins
they break down the peptide bonds between amino acids
they can also break down nucleic acids and sugars
describe the range in 1/2 life of proteins around the body
Protein stability (1/2 life) varies from a few minutes (e.g. cyclins which regulate mitosis) to a lifetime (proteins in the lens of the eye)
when proteins in the lense of our eye die you get cataracts .
what does protein 1/2 life refer to
Protein half-life refers to an experimental measurement: The time that half of the original population of protein remains. Or the time that half of the original population of protein has been degraded.
why are proteins degraded
theres 5
to regulate the function/activity of a protein and therefore the cell. E.g., ion
channels and transporters in epithelia to change ion transport pathways.
to allow replacement with new proteins.
to inactivate them e.g., ligands, cell cycle proteins.
to recycle amino acids of nonfunctional proteins e.g., misfolded or misassembled proteins in the ER.
as they are extracellular proteins from pathogens
why do different proteins have different 1/2 lifes
Lifetime of a protein depends on the function of a protein and the cellular
pathway it is involved in.
what degrades proteins
Degraded in the lysosome or the proteasome
what do lysosomes break down
extracellular or transmembrane proteins brought into the cell by endocytosis and
aged or defective organelles (also called autophagy)
what is autophagy
it is when a lysosome breaks down aged or defective organelles
what does the lysosome contain
Contain enzymes (acid hydrolases) that work best at acidic pH (not in cytosol). The enzymes break down proteins, sugars and nucleic acids.
what is the main enzyme that lysosomes contain
acid hydrolases
how does the lysosome maintain its low pH
Two transport proteins pump H+ and Cl- into the lysosome
what does autophagy mean
self eating
describe the process of autophagy
Uptake of random area of cytoplasm or defective organelles (phagophore)
Phagophore forms a complete ‘vesicle’ (autophagosome)
Autophagosome begins to fuse with lysosome
Autolysosome formed, degradation begins
Organelles and any uptake substances degraded and recycled
what is the difference between a phagophore, autophagosome and a autolysosome
phagophore = the beginning of engorgement and is the start of the formation of an autophagosome
an autophagosome is when the phagophore has completely engulfed the organelle in a continuous membrane
an autolysosome is when the autophagosome and lysosome come together and the contents of both mixes
what is the difference between ubiquitin-proteasome system for protein degradation and autophagy
the ubiquitin system is highly controlled and not random like autophagy
what are 4 things ubiquitin-proteasome system does
Highly controlled process for degrading unwanted proteins, terminating or activating signaling pathways, regulating the cell cycle and providing an important source of amino acids for de novo protein synthesis.
Proteins are covalently tagged with a small 8kDa protein called ubiquitin which then leads to them being degraded
other than degradation, what else can ubiquitination lead to
endocytosis (monoubiquitin) or to change the location of a protein.
in the ubiquitin-proteasome pathway, what is E1, E2, and E3
E1 (activating enzyme),
E2 (conjugating enzyme)
E3 (ligase)
what is the role of E1, E2 and E3 in the ubiquitin-proteasome pathway
E1 catalyses the breakdown of ATP –> Amp which transfers ubiquitin onto the enzyme
E1 then transfers ubiquitin onto the E2 enzyme and then to the E3 enzyme
E3 then puts ubiquitin onto the protein
what is needed to remove ubiquitin from a protein
Deubiquitinating enzymes or DUBs remove ubiquitin from
proteins.
where are ubiquitinated proteins bound for
the protostome
what is the process of how ubiquitin and the protostome degrade a protein
Ubiquitin binds proteasome and orients the protein at the regulatory particle so that the protein comes dont into the protostome (which is shaped like a cylinder)
the protein is then degraded in proteasome by
peptidase
Peptides and amino acids are recycled
what is the protostome made up of
regulatory particle and a core particle
how does ubiquitin tagging promote endocytosis of ion channels
what are 2 examples of proteins regulated by this
- ENaC and ROMK1 are
monoubiquitinated, promoting endocytosis to the apical sorting
endosome
Ubiquitinated proteins trafficked onto common endosome where
fate of the channel is determined
Deubiquitination leads to recycling.
Ubiquitinated proteins move on to lysosome for degradation through the late endosome
what causes liddle’s syndrome to occur
In Liddle’s syndrome (hypertension) ENaC cannot be tagged with ubiquitin due to loss of the binding site for an E3 ubiquitin ligase.
Therefore less ENaC endocytosis, more ENaC at the plasma membrane and more Na+ reabsorption leading to high ECF volume and pressure
what is monoubiquitination
a single addition of a ubiquitin to a protein
what is multi-ubiquitination
a single ubiquitin at multiply sights on a protein
what is polyubiquitination
a chain of ubiquitin attached to a single amino acid of a protein
what part of the protein does ubiquitin bind to
Ubiquitin is covalently linked to lysines or to the N-terminal amino acid of the target/substrate protein.
what are monoubiquitination and multi-ubiquitination signals for
These are signals
for endocytosis or movement through the endosome system.
what is polyubiquitination a signal for
Chains of ubiquitin signal degradation of the target protein in the proteasome.
what enzymes do Lysosome, Proteasome, and Autophagy contain
Lysosome = Acid hydrolases
Proteasome = Peptidases
Autophagy = Acid hydrolases
what do Lysosome, Proteasome, and Autophagy degrade
Lysosome = proteins, sugars, DNA/RNA
Proteasome = Proteins (ubiquitin recycled)
Autophagy = Damaged organelles, microbes, cytosolic components
describe the regulation of Lysosomes, Proteasomes, and Autophagy
Lysosome = Somewhat random, ubiquitin tagging
Proteasome = Highly regulated
Autophagy = Random, but some regulated
what are the different cofactors between Lysosomes, Proteasomes, and Autophagy
Lysosome = no cofactors
Proteasome = Requires a series of three enzymes: E1, E2 and E3
Autophagy = no cofactors
what are the general targets of Lysosomes, Proteasomes, and Autophagy
Lysosome = Cell surface and extracellular proteins
Proteasome = Cytoslic, nuclear, ER proteins (ERAD)
Autophagy = Cytosolic
components
what is the structure of Autophagy
Autophagy = Double membraned
autophagosome
Lysosomes only degrade proteins
BECAUSE
monoubiquitin is used as a tag for degradation in the endocytosis pathway
the first statment is false and the second is true
the first statment is false because of the work only
