7.21-7.30 Flashcards
primary site of synthesis of cell’s phospholipids
ER
what pathway is used to make phospholipids?
Kennedy pathway
Kennedy pathway
2 fatty acyl CoA attached to glycerol 3-P to form diacylglycerol, which is hydrophobic enough to insert in c-face of membrane
how are polar heads added to DAG
head group is phosphorylated first by CDP, then head group + P is transferred to DAG, releasing CMP
most abundant membrane p-lipid
phosphatidylcholine
what bond is formed between fatty acids and glycerol
ester linkage
other types of phospholipids made by Kennedy pathway
phosphatideylethanolamine, phosphatidyl inositol, and sometimes phosphatidylserine
where can PE also be made?
mitochondria - from modifying PS that came from ER
what is responsible for transport of PS from ER to mito?
mitochondrial associated membrane
mitochondrial associated membrane
specialized ER that is very close to mito, making close contact with its membrane
where does most sterol (cholesterol) synthesis occur?
ER
following phospholipids’ synthesis in the ER, some must be transferred to ____ other membranes in the cell _______ _____________
all, not randomly
phospholipid transfer proteins
thought to move lipids from one bilayer to another
- can’t account for membrane growing, after they bring lipid to membrane they leave with a different one
flippases
needed to flip about half of newly-synthesized lipids from ER c-face to non-c-face
are flippases random?
can be, but other phospholipid translocators must be more selective
ex. of phospholipid concentration difference in membrane
- non-c-face of PM: PC
- c-face: PS, PE, PI (except for GPI-anchored)
morphological characteristics of ER
- large, flat sheets (cisternae) - RER
- long, curving tubules - SER
where are the sheets of the ER usually found
next to nuclear envelope
where do tubules of ER extend
in network throughout cell, contacting other organelles and PM
RER
especially abundant in cells which secrete proteins like Ig (plasma B cells) and hormones (B-islets of Langerhans)
what is SER responsible for
- lipid metabolism steroid synthesis
- glycogen metabolism
- drug detoxification
SER is especially abundant in which cells?
- those that secreted steroid hormones (Leydig cells, ovary follicular cells)
- liver hepatocytes
true or false: SER increases with increase in drug use
true
SR (sarcoplasmic reticulum)
in skeletal muscle cells, stores intracellular Ca2+, contains calsequestrin
calsequestrin
protein that has several Ca2+ binding sites in SR
other examples of Ca2+-binding protein in non-ms. cells
- calreticulin
- calnexin
- BiP
- PDI
calreticulin is both a _____________ and a ___________________
glycoprotein chaperone and a Ca2+-binding protein
BiP, calnexin, calreticulin function __________ efficiently when ER Ca2+ stores are depleted
less
prolonged calcium depletion in the ER can induce what?
UPR
how is UPR induced?
- Ca2+ ER stores deplete3d
- BiP, calreticulin, etc. less efficient
- less chaperones to fold proteins
- induce UPR to make chaperonins
Ca2+ release from ER is sometimes implicated in triggering _____________
apoptosis
tubular elements of the ER are in continual flux, and are often aligned to _____________
cytoskeleton
true or false: cytoskeleton not required for formation of tubules/networks in vitro
true
cytoskeleton role for ER networks
after it forms, it is properly distributed
cells are able to regulate the ________ and ________ of their ER (rapidly)
size, shape
response of cell to increase in drug like phenobarbital
SER expands to remove the drug
ex. of cells regulating size/shape of ER
- drug increase
- B-cell activation
- mitosis/meiosis
what happens to RER when B-cell activated and differentiation to plasma and memory B-cells occurs
plasma-B cells proliferate their RER to secrete large amounts of Ig proteins
when does the ER sometimes fragment
during mitosis/meiosis, then partitioned into progeny cells
signal sequence for nucleus
internal signal patches consisting of non-contiguous aa residues brought together by tertiary/quaternary structure
true or false: nuclear localization signals are removed after import through nuclear pore complexes
false
why are NLS not removed?
- many proteins might need signal again if they are outside after telophase
- difficult to remove internal signals
which organelles can import folded proteins
nucleus, peroxisome
which organelles must imported unfolded proteins
mitochondria, chloroplasts
TOM
translocase of outer membrane (mito)
TIM
translocate of inner membrane (mito)
mitochondrial targeting signal
N-terminal amphipathic alpha-helical stretch of 20-50 aa residues
- hydrophobic sequences on side of helix, basic aa residues on other side
what is required to get into the matrix
ATP and charge difference (electrochemical gradient)
what is necessary to prevent folding of protein prior to translocation for both mito and chloro
chaperone cytosolic hsp70
true or false: protein going into mito is 100% unfolded
false - still need to keep alpha-helical stretch
- unfolded right as going into translocase
purpose of TOM and TIM being in close proximity
so proteins don’t dissociate into intermembrane space
mtHsp70
binds protein as it emerges from channel
- acts as ratchet or motor
- requires ATP energy
where does membrane potential across inner membrane come from
ETS
what are mt-signal sequences cleaved by
soluble mitochondrial processing protease (MPP)
Oxa1p pathway
integrates transmembrane IMPs in mt-inner membrane from mito matrix
true or false: first targeting sequence is removed once protein gets into mito matrix
true
how many signals to get to mito matrix from cytosol
1
how many signals to get to inner membrane from cytosol
2
TOC
translocon of outer envelope of chloroplasts - met by pre protein first
TIC
translocon of inner envelope of chloroplasts - attached to TOC
TAT (Twin-Arginine-translocation) system
uses second signal sequence once protein in storm to get protein into thylakoid membrane or lumen
what does translocation across thylakoid membrane require
- electrochemical gradient
- pH gradient
PTS1 signal
peroxisome C-terminal
PTS2
peroxisome N-terminal
what happens to peroxisomal signal receptor
carried into peroxide also, then exported alone to be used again
why does peroxisome translocation need to be tightly regulated
internal environment of peroxisomes would be toxic to the cell
