Metabolism 7 Flashcards

1
Q

What are the 3 types of intracellular transport?

A
  1. Gated transport (e.g. nuclear)
  2. Trans-membrane transport (e.g. import of newly synthesised proteins into ER)
  3. Vesicular transport (inter-organellar transport)
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2
Q

Describe vesicular transport.

A

Exocytosis:

ER -> Cis -> Medial -> Trans -> Cell surface via various secretory vesicles

Endocytosis:

Pathway 1 = early endosome (involved in recycling), material can keep recirculating back to plasma membrane

  • it could go to the late endosome.
  • if material is destined for destruction it will be taken to the lysosome
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3
Q

Which golgi section is closest to ER?

A

cis

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4
Q

Where does post translational modification occur?

A

Golgi

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5
Q

Where do the ribosomes come from, that synthesise proteins that stay in the cytosol and also those that are transported into the ER?

A

Common Pool

At the end of each round of synthesis, ribosomal subunits are released and rejoin the common pool

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6
Q

What are some post translational modifications that are made?

A
  1. Folding
  2. Disulphide bond formation
  3. Glycosylation
  4. Proteolytic cleavages
  5. Assembling multimeric proteins
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7
Q

What happens if something goes wrong in modification?

A

Unassembled/misfolded proteins are retained and they are exported back into the cytosol where they are degraded.

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8
Q

What is CFTR?

A

ABC transporter-class Cl channel in epithelial cell membranes.

Most common mutation is delta f508, which causes deletion of 3 nucleotides and loss of phenylalanine.

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9
Q

Where are proteins sorted into vesicles?

A

Trans golgi network

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10
Q

What are the functions of golgi?

A
  1. Folding
  2. Protection
  3. Receptors
  4. Recognition
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11
Q

What 3 signals do proteins have to ensure they get to the correct compartment?

A
  1. Targeting/sorting signals
  2. Retention signals
  3. Retrieval signals
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12
Q

What are the 2 pathways for proteins to leave the cell?

A
  1. Constitutive pathway

2. Regulated secretory

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13
Q

Describe how lysosomal enzymes are sorted at the golgi network.

A
  1. Proteins destined to become lysosomes recognised in cis golgi network.
  2. Lysosomal hydrolase precursors are recognised in the cis golgi network.
  3. Carbohydrates on Lysosomal hydrolase precursor are modified by addition of a phosphate to the carb, acting as a TAG.
  4. Mannose phosphorylation occurs, catalysed by phosphotransferase.
  5. Lysosomal enzymes now tagged with a phosphorylated sugar.
  6. They now go to trans golf network, where the phosphorylated sugar is detected by Mannose-6-Receptor. Enzymes consequently packaged into very specific vesicles.
  7. Vesicles have targeting signals which are lysosome specific. Vesicles first go to late endosome.
  8. Late endosome has a proton pump, which pumps cytoplasmic protons into the late endosome. This gives the late endosome lumen acidic pH.
  9. Acidic environment causes M6P to release phosphorylated lysosomal hydrolyses.
  10. After release, phosphate removed (via phosphohydrolase). THIS MEANS THE LYSOSOME CANNOT GO BACK TO GOLGI AS ITS LOST ITS PHOSPHATE.
  11. This causes accumulation of lysosomal hydrolyses in late endosome.
  12. Late endosome matures to form a lysosome.
  13. M6P receptors recycled back to trans golgi network.
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14
Q

What are the 3 types of endocytosis.

A
  1. Receptor mediated endocytosis - substances bind to specific receptors, forming vesicles that have a protein coat around them
  2. Pinocytosis - fluid drinking. Cell extends its membrane and takes in some extracellular fluid
  3. Macropinocytosis/Phagocytosis - can take up large particles, e.g. bacteria
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15
Q

What can happen to early endosomic material (the sorting compartment)?

A
  1. Recycling - material sent back to plasma membrane
  2. Degradation
  3. Transcytosis - material carried to basolateral membrane, where it is moved across epithelial monolayer.
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16
Q

Give an example of the degradation pathway.

A
  1. LDLs carry lipids and cholesterol to cells
  2. Protein component of LDLs recognised by receptors on cell surface.
  3. The receptors accumulate in pits surrounded by a protein coat (Clathrin)
  4. The protein pits invaginate and pinch off and form Clathrin-coated vesicles.
  5. Clathrin coating falls off inside the cell, and the uncoated vesicle fuses with the early endosome.
  6. LDLs in early endosome are transferred to lysosomes where they are degraded - produce free cholesterol.
  7. LDL receptor recycles back to plasma membrane, ready for another round of endocytosis.
17
Q

How is familial hypercholesterolaemia caused?

A

Mutation in LDL receptor.

18
Q

What do vesicles move along?

A

The cytoskeleton