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PROTEIN SECRETION BY
HEPATOCYTES
Danny Taheri
Linda Amo-Mensah
Vishal Kinkhabwala
Andrea Whitley
THE QUESTION:
• Beginning with protein synthesis in
membrane-bound ribosomes, hepatocytes
secrete proteins into the circul...
PROTEIN SYNTHESIS AND SECRETION
• Central Dogma of
Biology: DNA  mRNA
 PROTEIN
• DNA is transcribed into
mRNA in the nuc...
TRANSLATION
• The mRNA is translated
into protein in the
ribosome through the
action of adding Amino
Acids to make a
polyp...
Post-Translational Modification
• The polypeptide is then
released into the
cytoplasm, ready for posttranslational
modific...
Free vs. Membrane-Bound Ribosomes
• FREE:
• Proteins formed from
free ribosomes, are
released into the
cytosol and used wi...
Free vs. Membrane-Bound Ribosomes
• MEMBRANOUS
• They are attached to the cell
and synthesize proteins in the
membranous c...
HEPATOCYTES
• Primary cell type in the
liver
• One major function is
synthesis and secretion
of Plasma Proteins
SECRETED PROTEINS
• 1. Albumin: Maintains
osmotic pressure
• 2. Alpha-Fetoprotein:
High levels detected in
congenital anom...
SECRETED PROTEINS
• 5. Plasminogen:
• Thrombolitic – breaks
down clots
• Active form of Plasmin

•
•
•
•

6. Clotting Fact...
BACK TO THE QUESTION
• Beginning with protein synthesis in membranebound ribosomes, hepatocytes secrete proteins
into the ...
A: Active Transport through the Cell
Membrane
• WHY It Could Be:
• Proteins would have to cross through a cell membrane to...
B: Diffusion through the Cell
Membrane
• WHY It Could Be:
• Proteins would need to cross cell membrane to exit cell

• WHY...
C: Transport by Microtubules and
Exocytosis
• WHY It could be:
• Exocytosis (through vesicles) is a MAJOR component of
pro...
E: Transport through Pores in the Cell
Membrane
• WHY It could be:
• Release of certain substances from a cell does move t...
D: Transport in Vesicles and
Exocytosis
• WHY It Is:
• Proteins are packaged into vesicles and then released from
the memb...
References
• Boron, W. F., & Boulpaep, E. L. (2009). Uptake, Processing, &
Secretion of Compounds by Hepatocytes. In Medic...
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PROTEIN SECRETION BY HEPATOCYTES

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PROTEIN SECRETION BY HEPATOCYTES

  1. 1. PROTEIN SECRETION BY HEPATOCYTES Danny Taheri Linda Amo-Mensah Vishal Kinkhabwala Andrea Whitley
  2. 2. THE QUESTION: • Beginning with protein synthesis in membrane-bound ribosomes, hepatocytes secrete proteins into the circulation via which of the following mechanisms? • • • • • A: Active transport through the cell membrane B: Diffusion through the cell membrane C: Transport by microtubules and exocytosis D: Transport in vesicles and exocytosis E: Transport through pores in the cell membrane
  3. 3. PROTEIN SYNTHESIS AND SECRETION • Central Dogma of Biology: DNA  mRNA  PROTEIN • DNA is transcribed into mRNA in the nucleus • mRNA is then TRANSLATED into a protein by the ribosomes in the cytoplasm
  4. 4. TRANSLATION • The mRNA is translated into protein in the ribosome through the action of adding Amino Acids to make a polypeptide • These ribosomes can either be Free Polysomes in the cytoplasm, or Membrane-Bound Ribosomes, attached to the Rough Endoplasmic Reticulum
  5. 5. Post-Translational Modification • The polypeptide is then released into the cytoplasm, ready for posttranslational modifications • The proteins then enter the Golgi Apparatus, where they are packaged into vesicles, which then move to the plasma membrane, where they are released into circulation
  6. 6. Free vs. Membrane-Bound Ribosomes • FREE: • Proteins formed from free ribosomes, are released into the cytosol and used within the cells • They are moved about anywhere in the cytosol but are excluded from the cell nucleus.
  7. 7. Free vs. Membrane-Bound Ribosomes • MEMBRANOUS • They are attached to the cell and synthesize proteins in the membranous cell organelles • The organelles they bound to are rough endoplasmic reticulum. • The newly produced polypeptide chains are inserted direct into the rough endoplasmic reticulum by the ribosome undertaking vectorial synthesis and are then transported to their various destinations through the secretory pathways. • Bound ribosomes usually produce proteins that are used within the plasma membrane or are expelled from the cell via exocytosis
  8. 8. HEPATOCYTES • Primary cell type in the liver • One major function is synthesis and secretion of Plasma Proteins
  9. 9. SECRETED PROTEINS • 1. Albumin: Maintains osmotic pressure • 2. Alpha-Fetoprotein: High levels detected in congenital anomalies (i.e. spina bifida) • 3. C-Reactive Protein: Major role in inflammatory response • 4. Transferrin: Transfers iron from duodenum to body tissues
  10. 10. SECRETED PROTEINS • 5. Plasminogen: • Thrombolitic – breaks down clots • Active form of Plasmin • • • • 6. Clotting Factors Most important: CF 1: Fibrinogen CF 2: Prothrombin
  11. 11. BACK TO THE QUESTION • Beginning with protein synthesis in membranebound ribosomes, hepatocytes secrete proteins into the circulation via which of the following mechanisms? • A: Active transport through the cell membrane • B: Diffusion through the cell membrane • C: Transport by microtubules and exocytosis • D: Transport in vesicles and exocytosis • E: Transport through pores in the cell membrane
  12. 12. A: Active Transport through the Cell Membrane • WHY It Could Be: • Proteins would have to cross through a cell membrane to exit the cell (Wang and Boyer, 2004) • ATP (is a component of active transport) is often a component of protein secretion (Chen and Tai, 1985) • WHY It Isn’t: • Movement through the Golgi Apparatus would involve vesicles, and active transport does not use vesicles • No gradients or pumps  No Active Transport used (Wang and Boyer, 2004)
  13. 13. B: Diffusion through the Cell Membrane • WHY It Could Be: • Proteins would need to cross cell membrane to exit cell • WHY It Isn’t: • Passive Diffusion is not possible due to the polar nature of proteins and their inability to freely cross the phospholipid bilayer (Wang and Boyer, 2004)
  14. 14. C: Transport by Microtubules and Exocytosis • WHY It could be: • Exocytosis (through vesicles) is a MAJOR component of protein secretion • WHY It isn’t: • NO use of microtubules seen in this process (Wang and Boyer, 2004)
  15. 15. E: Transport through Pores in the Cell Membrane • WHY It could be: • Release of certain substances from a cell does move through pores • WHY It isn’t: • Protein synthesis and secretion does not usually go through pores but rather bud off through membrane vesicles (Wang and Boyer, 2004)
  16. 16. D: Transport in Vesicles and Exocytosis • WHY It Is: • Proteins are packaged into vesicles and then released from the membrane via exocytosis (Wang and Boyer, 2004) • Consistent with examination of the overall process!
  17. 17. References • Boron, W. F., & Boulpaep, E. L. (2009). Uptake, Processing, & Secretion of Compounds by Hepatocytes. In Medical physiology: A cellular and molecular approach. Philadelphia, PA: Saunders/Elsevier. • Chen, L., & Tai, P. (1985). ATP is essential for protein translocation into Escherichia coli membrane vesicles. Proceedings of the National Academy of Science, 82, 4384-4388. • University of Washington (2012). Cell Secretion. Retrieved from http://courses.washington.edu/conj/cell/secretion.htm • Wang, L., & Boyer, J. (2004). The Maintenance and Generation of Membrane Polarity in Hepatocytes. Science Frontier, 39(4), 892899.

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