#31 Biochemistry Membrane Transport Lecture for Kevin Ahern's BB 451/551

1. Contact - [email protected] 2. Kevin's lectures with The Great Courses - https://www.thegreatcoursesplus.com/b... 3. Kevin's Lecturio videos for medical students - https://www.lecturio.com/medical-cour... 4. Course materials at https://kevingahern.com/biochemistry-... 5. Course video channel at    • #28 Biochemistry Citric Acid Cycle Lecture...   6. Metabolic Melodies at https://teeheetime.com/category/lyric... 7. Kevin's Free Biochemistry books - https://kevingahern.com/biochemistry-... 8. Kevin's Pre-med Audio course on Listenable - https://listenable.io/web/courses/143... 1. Cellular membranes are fluid in nature. Shorter, more unsaturated fatty acids make for membranes that retain fluidity at lower temperatures compared to longer, saturated fatty acids. Fish membranes are full of unsaturated and polyunsaturated fatty acids, which makes them fluid at fairly low temperatures. 2. The midpoint of the conversion between the solid and the fluid state is referred to as the Tm. Cholesterol is often found in membranes. Though it does not change the Tm of a membrane it does widen the range of the transition temperature. 3. Not all molecules move into a cell through specific protein receptors. An example is cholesterol, which enters cells via LDLs that attach to a receptor on the cell's surface. The entire LDL with the cholesterol is taken into the cell in a process called endocytosis. Highlights of Membrane Transport 1. Diffusion is a process in solutions where molecules move from a high concentration to a low concentration. Active transport occurs when a least one molecule is moved across a membrane from a low to a higher concentration. This takes energy. 2. We break transport across membranes into two main categories - 1) passive transport (diffusion driven), and 2) active transport (an energy-requiring process). 3. Active transport moves at least one molecule in the opposite direction of where diffusion would operate. 4. ATP is a primary energy source for active transport, but there are other sources, as well. Pumps that move two molecules in the same direction across a membrane are called symports, whereas pumps that move two molecules in opposite directions across a membrane are called antiports. Pumps are called electroneutral if their action does not result in a net change in charge and electrogenic if their action changes the charge across the membrane as a result of their action. 5. An example of a passive transport system is a glucose transporter in blood cells that simply lets glucose diffuse into cells. No energy is required for that particular transporter. Other glucose transporters in other cells are active in that they use energy to move glucose against a concentration gradient. 6. P-type ATP-using transport systems use phosphoaspartate as a covalent intermediate in their mechanism of action. 7. The mechanism of transport of the Ca/ATPase pump includes binding of ATP and the relevant ions, transfer of phosphate from the ATP to the protein, conformational change in the protein causing movement of the ions across the membrane, hydrolysis of the phosphate from aspartate in the protein, a second conformational change to bring the protein back to its original state. 8. The Na/K ATPase transports three sodiums out of the cell and two potassiums in for each cycle. Movement of Na and K is essential for the cell being able to maintain osmotic balance. The Na/K ATPase is called an antiport because it moves molecules in opposite directions. 9. Another class of transporter proteins that use ATP to move molecules are the ABC transporters. An example is the Multidrug Resistance Protein that is involved in the resistance of cancer cells to chemotherapy agents. They act by binding the compound first. This causes a conformational change in the protein that allows ATP to bind. Binding of ATP causes the protein to 'evert' (move its opening from one side of the membrane to the other). This has the effect of moving the bound compound to the outside of the cell. After this happens, ATP is hydrolyzed to change the protein to evert again and change back to its original conformation (opening facing inwards). 10. The Na+/Ca++ exchange pump is a secondary transporter. It uses movement of Na+ in to cells to be a driving force for pumping Ca++ out. If Ca+ is not pumped OUT, its concentration in muscle cells remains high, stimulating contraction. Digitoxigenin is a compound from foxglove that binds the Na+/K+ ATPase, preventing development of a Na+ gradient. As a consequence, digitoxigenin increases Ca++ concentration. Digitoxigenin is used as a heart stimulant.