BIO : Endoplasmic reticulum

how is the endoplasmic reticulum orgnized ?

into a netlike labyrinth of branching tubules and fkattened sacs extending througouht the cytosol

what do the ER membrane does ?

if forms a continuous sheet enclosing a single internal space. ER membrane is continuous with the nuclear envelope

what is the ER lumen ?

internal compartment of the ER. it occupies more than 10% of the total cell volume

what are the two distinct ER ?

• smooth ER (SER)

• rough ER (RER)

what is the difference between the two ER ?

• the smooth ER surface lacks ribosomes

• the rough ER has ribosomes

what is the functions of ribosomes ?

protein folding and assembly, protein modification and protein transport

of what are made ribosomes ?

RNA and protein

what is the site of protein synthesis ?

ribosomes

where could ribosomes be ?

• bound to the ER (rough)

• bound to the nuclear envelope

• free in cytoplasm

what do membrane-bound ribosomes do ?

synthesis of proteins that are being concurrently translocated into the ER

what do free ribosomes do ?

synthetise all other proteins

what are the subunits of ribosomes ?

two unequal subunit

where are ribosomal subunits assembled ?

at the nucleolus

how are ribosomal subunits assembled ?

association of newly transcribed and modified rRNAs with ribosomal protein

eukaryotic ribosomes and prokaryotic ribosomes are the same ?

no, prokaryotic ribosomes are smaller

what is the utility of the difference in size between eukaryotic and prokaryotic ribosomes ?

antibiotic drugs such as strepromycin and erythromycin use this difference as mechanism of action

define co translational translocation ?

protein translocation beginning before the polypeptide chain is completely synthesized and when a ribosome happens to be making a protein with an ER signal sequence, the signals directs the ribosomes to the ER membrane.

what are the components that guide the ER signal sequence to the ER membrane ?

• a signal-recognition particle (SRP), which binds to the ER signal sequence

• an SRP receptor : an integral membrane protein complex in RER membrane

what are the steps of co-translational translocation ?

• SRP binding the ER signal seqeunce cases a pause in synthesis

• SRP-ribosome compelx binds to the SRP receptor

• this interaction brings the SRP-ribosome complex to a protein translocator

• the SRP and SRP receptor are then released and growing polyppetide chain goes across membrane

what happens after the protein has been completely translocated ?

• pore closes

• translocator opens latterally in lipid bilayer

• the hydrophobic signal sequence to diffuse in the bilayer

• then its degraded to amino acids

how does the stop-transfer sequence works ?

• it enters the translocator

• interacts with binding site

• change conformation and discharges the protein into lipid bilayer

• singal sequence is cleaved

what is the cause of single-pass transmembrane protein ?

internal signal sequence that are not cleaved

define double-pass ?

internal ER sequence acting as a start-transfer signal initiates the transfer of the C-terminal

define multipass ?

second start-transfer sequence reinitiates translocation further down the polypeptide chain until the next stop-transfer

what can maintain proteins in unfolded conformation ?

cytosolic chaperones

what are the proteins present in the ER ?

• protein disulfide isomerase (PDI)

• chaperone protein (BiP)

what are protein disulfide isomerase (PDI) ?

ER protein that catalyses the oxdiation of free sulfhydryl (SH) groups on cysteines to form disulfide (S-S) bonds

what is Chaperon protein (BiP) ?

bind to the unfolded polypeptide chain as it crosses the ER membrane and then mediates protein folding and assembly of multi-subunits

what happen to abnormally folded or improperly assembled proteins ?

they remain bound to BiP and are consequently retained within the ER or degraded

name of protein when properly folded ?

oligomeric state

what happen to proteins exported from the ER back into the cytosol ?

degraged in proteasomes

what happen when accumulation of unfolded protein ?

unfolded protein response

what does the unfolded protein response do ?

increase transcription of genes encoding ER chaperones and enzymes involved in ER protein degradation

polypeptide chain glycosylated on ____ ____ ____ ?

asparagine amino acids

what happens to a precursor protein immediately after the completion of protein synthesis ?

precursor proteins remains anchored in the ER membrane by a hydrophobic C-terminal sequence

how long does it take fro precursors protein to be processed after synthesis ?

within less than a minute

what happens simultaneoulsy when the enzyme cuts the protein free ?

a new c-terminus is attached to amino group on GPI

function of smooth endoplasmic reticulum ?

• lipid and lipoprotein synthesis

• detoxification of drugs and harmful compounds produced by metabolism

• sequester Ca2+ from the cytosol

which lipoproteins does SER produce ?

hepatocyte (liver)

where is the enzyme for lipid components production located in SER ?

in the membrane

which enzymes are involved in detoxification in the smooth ER ?

enzymes catalysing reactions that make water-insoluble compounds water-soluble

why is it important to render water-insoluble compounds water-soluble ?

to prevent toxic accumulation in cell membrane and allow the compounds to leave the cell and be excreted in the urine

what happens to the smooth ER when large quantities of drugs enter the circulation ?

detoxification enzymes are synthesized in large amounts, and the smooth ER doubles in surface area within a few days

what happens to the excess smooth ER membrane onde the drug is removed ?

the excess SER membrane is rapidly removed by autophagy

name of smooth ER in muscle cells ?

sarcoplasmic reticulum

what does release and reuptake of Ca2+ trigger ?

contraction and relaxation of myofibrils during muscle contraction

where are enzymes catalysing each step of phospholipid synthesis situated ?

in the ER membrane, with active sites facing the cytosol

what is the role of acyl transferase in lipid metabolism ?

acyl transferase transfer two fatty acids from coenzyme A carriers to glycerol-3-phosphate, yielding phosphatidic acid

where is phosphatidic acid inserted after it is formed ?

into the membrane

what enzyme converts phosphatidic acid into diacylglycerol ?

phosphatase

what happens to diacylglycerol after its transformation ?

polar head groups are attached to diacylglycerol to form phosphatidylcholine, phosphatidylserine…

name of transmembrane phospholipid translocator required to transfer lipid from cytosol to lumen ?

scramblase

what do flippases do at the plasma membrane ?

flippases move specific phospholipids from the outer leaflet to the inner leaflet of the membrane

what energy do flippases use to work ?

ATP

results of flippase activity ?

asymmetric lipid bilayer

how is ceramide made ?

ceramide is made by condensing serine (an amino acid) with a fatty acid to form sphingosine, then adding a second fatty acid

where is ceramide sent after its synthesis ?

golgi apparatus

which molecules are synthesised from ceramide in the golgi ?

• glycolipids

• sphingomyelin

wher are glycolipids and sphingomyelin found in the lipid bilayer ?

exclusively in the non-cytosolic leaflet bc they r not substrate for lipid translocators

protein of mitochondria, plastids and peroxisomes are imported from where ?

cytosol

what is the normal equilibrium in the ER under physiologic conditions ?

a balance between the ER’s protein load and its folding capacity

what is ER stress and what can cause it ?

• increased protein synthesis

• accumulation of misfolded proteins

• changes in calcium or redox balance in the ER

how do cells respond to ER stress ?

cells activate an adaptative signaling pathway called the unfolded protein response (UPR) or ER stress response

what happens if ER is prolonged or severe ?

the UPR triggers apoptosis, contributing to diseases like cancer, type 2 diabetes, neurodegeneration and atherosclerosis

what pathway are interconnected with ER stress under pathological conditions ?

• inflammation

• oxidative stress

what happens in the ER during protein overload ?

reactive oxygen species (ROS) are generated

what effect do ROS have on calcium ?

ROS cause calcium to be released into the cytosol, which then enters mitochondria

what happens when calcium enters mitochondria ?

it lead to cytochrome c release, altered membrane potential, eventually triggers apoptosis