Question 2

College Answer

This question examined core cellular physiology knowledge. This knowledge is crucial as it underpins much of the electrochemical responses within the syllabus. Mechanisms of diffusion and the role of individual pathways were well presented in many responses. Answers that scored well generally classified the mechanisms of transport into active and passive processes which ensured an appropriate breadth of answer. Many answers failed to provide any examples which was requested. The structure of the Na+/K+ ATPase pump was less well described, however pleasingly most candidates were able to accurately articulate its role and function.

Discussion

• Transport of molecules into (and out of) the cell can take three main forms:
• Diffusion:
  • Passive ("simple") diffusion: occurs along a concentration gradient directly through the lipid bilayer. Example: Oxygen and carbon dioxide molecules.
  • Facilitated diffusion: occurs along a concentration gradient, but requires a protein channel as a conduit. Example: aquaporins
  • Ion channels:  selective conduit proteins, usually gated, which only allow the passage of specific ions, usually in response to a triggering stimulus. Example: voltage-gated sodium channels.
• Active transport:
  • Primary active transport: mediated by a "pump" protein which uses chemical energy stored in ATP to facilitate the transport of molecules (usually against their concentration gradient). Example: sodium and potassium transport by Na⁺/K⁺ ATPase.
  • Secondary active transport: mediated by an exchaner or co-transporter which facilitates the movement of molecules using the energy of a concentration gradient set up by another (primary) ATP-powered transport process. Example: sodium and glucose co-transport.
• Vesicle transport
  • Endocytosis: where the transport of substances into the cell occurs by formation membrane-bounded vesicles containing the substance. Example: catecholamine neurotransmitter reuptake.
  • Exocytosis: the opposite of endocytosis, where vesicles transport molecules to the cell surface and empty their contents into the extracellular fluid.  Example: catecholamine neurotransmitter release.

Now, for 25% of the mark, about that ATPase:

• The Na⁺/K⁺ ATPase pump is a heteromeric transmembrane protein of three subunits with a total molecular mass of around 170 kDa.
• It switches between two states (a state of high sodium affinity, and a state of high potassium affinity) which allows it to swap ions across the cell membrane
• It binds three cytoplasmic sodium atoms, releases them through the extracellular pore, then binds two potassium atoms and releases them through the cytoplasmic pore.
• The state switch requires ATP to phosphorylate the protein.

Wilson, David B. "Cellular transport mechanisms." Annual review of biochemistry 47.1 (1978): 933-965.

Yang, Nicole J., and Marlon J. Hinner. "Getting across the cell membrane: an overview for small molecules, peptides, and proteins." Site-Specific Protein Labeling. Humana Press, New York, NY, 2015. 29-53.

Stein, Wilfred. Transport and diffusion across cell membranes. Elsevier, 2012.

Cussler, E. L., Rutherford Aris, and Abhoyjit Bhown. "On the limits of facilitated diffusion." Journal of membrane science43.2-3 (1989): 149-164.

Wu, Ling-Gang, et al. "Exocytosis and endocytosis: modes, functions, and coupling mechanisms." Annual review of physiology 76 (2014): 301-331.

Clausen, Michael V., Florian Hilbers, and Hanne Poulsen. "The structure and function of the Na, K-ATPase isoforms in health and disease." Frontiers in physiology 8 (2017): 371.

Rice, William J., et al. "Structure of Na+, K+-ATPase at 11-Å Resolution: Comparison withCa2+-ATPase in E1 and E2 States." Biophysical Journal 80.5 (2001): 2187-2197.

Møller, Jesper V., Birte Juul, and Marc le Maire. "Structural organization, ion transport, and energy transduction of P-type ATPases." Biochimica et Biophysica Acta (BBA)-Reviews on Biomembranes 1286.1 (1996): 1-51.