1-4 Tricarboxylic Acid Cycle Flashcards
ER fxns
- synthesis / glycosylation of: integral membrane proteins, secreted proteins, lysosomal enzymes
- calcium storage
- lipid synth
- steroid synth
- drug detox
- surface for metabolism*
Smooth: does not do protein folding
Golgi fxns
-Glycosylation, sorting, packaging of protiens and lipids for secretion or targeting to intracellular membranes and membrane enclosed compartments
Protein transport into the ER
mRNA-ribosome undergoing translation produces a Rignal Recognition Particle (SRP) on growing polypeptide, SRP bind to SRP receptor (located next to translocation channel) in the ER membrane, SRP displaces and recycled, translation continues through the translocation channel into the ER lumen, chaperone proteins on the lumen side bind the translating protein to assist in their folding and prevent premature PTMs
Can contain a signal sequence, which binds to translocation channel during translation, that is cleaved by signal peptidase allowing channel to close and protein to be deposited into ER
Protein glycosylation in ER
Asparagine side chain linked (amide linkage) to oligosaccaride (composed of glucose, mannose, N-acetylclucosamine)
Sugar must be synth in cytosol and is bound to ER-membrane embedded dolichol to flip into Lumen
Oligosaccaride protein transferase: enzyme to add sugar to asparagine for glycosylation
GPI anchor attachment
Glycosylphosphatidyl-inositol: ER membrane enbedded with inositorl sugar chain on lumen side
Protein embedded in ER membrane can be cleaved AT CARBOXY TERMINUS and attached to GPI
Protein folding cycle in ER
Unfolded: gets glucose chain attached to oligosaccaride, cycles to calnexin (membrane enbedded, lumen side binds protein and glucose to help fold), released as incomplete fold
Incompletely folded: glucosyl transferase moves glucose around to next part that needs special folding attention, glucose extracted from UDP-glucose to add to protein, cycles back to clanexin, continues until a normally folded and unglycosylated protein ready to exit ER
Vesicular transport (2)
Exocytosis: out of
Endocytosis: in to
Coat assembly
Cargo receptors in ER membrane bind cargo molecules, clathrin coat attached on cytosol side of receptor, bud formation with help of adaptor protein, pinched off for vesicle formation, clathrin and adaptor protein coat falls off, naked transport vesicle ready
Vesicle membrane fusion
Naked transport vesicle-Rab in cytosol
- Tethering: tethering protein on target membrane binds rab
- Docking: v-SNARE on vesicle binds t-SNARE on target membrane
- Fusion: happens and cargo protein delivered
ER-Golgi transport
Golgi-ER
- Cargo with an exit signal binds cargo receptor with extracellular exit signal
- COP2 coats receptors to form/bud off vesicle
- COP2 coat dissociates
- Vesicles merge into “vesicular tubular cluster” that is moved with motor protein towards golgi
- v/t SNAREs help fuse to golgi
- Golgi to ER same but uses COP1 coating, send resident ER proteins back to ER
Golgi-lysosome transport
- Lysosomal hydrolase precursor in golgi (sent from ER), binds with mannose
- P-GlcNAc added
- Uncovers Mannose-6-phosphate signal
- Binds M6P receptor
- Clathrin coat forms and buds off
- Clathrin coat falls off, “Receptor dependent transport”
- Fuses with early endosome
- Dissociates from receptor protein based on low pH in early endosome (established by proton pump)
- Phosphate removed
- Lysosomal hydrolase precursor free in early endosome
- M6P receptor buds off and recycled back to golgi
Endocytosis: Receptor mediated
ex. LDL
- LDL binding site on extracellular side of PM
- binds LDL vesicle
- Clathrin-caoted pit developed in cytosol side
- endocytoses
Endocytosis: phagosytosis
Requires actin cytoskeleton
Pseudopo engulfs
Macrophages
Endocytosis: fluid phase pinocytosis
Pinching off small vesicles from PM
Ex. viral infection, prion diseases, maternal antibodies across placenta, BBB
Endosome to Lysosome
Early endosome (always present, vesciles will fuse with)
Pathway #1: Entire early endosome with modify to become, late endosome, endolysosome, lysosome
Pathway #2: Microtubule mediated transport of multivesicular body, buds off from early endosome and modified to late endosome, endolysosome, lysosome
