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Hemo Part 2: You drive!

Hemo Part 2: You drive!. HemoBohrBabies. What you ’ ll learn today. How hemoglobin switches from oxygen-binding (lungs) to oxygen-releasing (muscles) The role of pH in this shape (conformation) switch How a single nucleotide change causes sickle cell anemia

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Hemo Part 2: You drive!

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  1. Hemo Part 2: You drive! • HemoBohrBabies

  2. What you’ll learn today • How hemoglobin switches from oxygen-binding (lungs) to oxygen-releasing (muscles) • The role of pH in this shape (conformation) switch • How a single nucleotide change causes sickle cell anemia • ...and you’ll think thoughts about hemoglobinopathies

  3. Thinking with your eyes

  4. Flask with Purple liquid • What do you notice? (observe) • Add drops of liquid 1 • What do you notice? What does that mean about your dripper solution? • What does it mean that it is now a different color? • Add more drops of liquid 1 • What do you notice?

  5. Now add drops of liquid 2 • What do you notice happening? • What must this mean about liquid 2? • Add more drops of liquid 2 • What do you notice? • How must liquid 2 compare to liquid 1?

  6. H+ H+ H+ H+ H+ pHand Histidine http://www.chemeddl.org/alfresco/d/d/workspace/SpacesStore/b73843fe-f422-4539-91fd-230d615d1faf/L-histidine-jmol.jpeg?guest=true

  7. Acids, bases, and you http://www.medicalinsider.com/acidosis.html

  8. pH in your life http://www.zazenessentialwater.com.au/images/alkaline-vs-acidic.jpg

  9. Your muscles are tripping on acid, man • Metabolism generates CO2 • CO2 + H2O => H2CO3 => H+ + HCO2- • Metabolism of sugar yields acidic (H+ liberating molecules) products

  10. What’s normal pH? • For lungs its: 7.38 to 7.42 • For the muscles it can range from 6.8 to 7.1 Sources: Lungs: https://microbewiki.kenyon.edu/index.php/Lungs  Muscles http://www.pnas.org/content/85/21/7836.full.pdf 

  11. Today’s Groups

  12. Beautiful on the inside? • Draw the highlights of woman-with-child’s circulatory system on your bench. Don’t forget baby. How’s he/she breathing in there? • (Write down your thoughts so you can refer back to them later in lab) • Make sure to draw the mother’s lungs. On the mother, label which parts of her body are lower in pH (higher [H+]) and higher in pH (lower [H+])

  13. Go! • Control Center => In-Lab Activities => Bohr, Babies & Sickles

  14. Mutation--not always bad • **Should this go here or at the end of this lab as a way to summarize what they have been looking at with hemoglobin? • While the comparison is often made, proteins are not sentences • An amino acid is a collection of properties; changing from one to another changes a region of the protein by (little/some/a lot/completely) • It’s an exaggeration, but think of amino acids more like different vacuum cleaner nozzles

  15. Histidine, pH, DPG and Fetal hemoglobin • How many Histidines are in the DPG binding site? What would the consequence of low pH (high [H+] be for DPG binding? • WHY does fetal hemoglobin bind DPG less effectively? • What is the consequence of fetal hemoglobin having less affinity for DPG in terms of ability to bind O2? (What conformation of Hb binds to DPG?)

  16. Hemoglobin and Sickle Cell • Remember there is a ‘greasy’ POCKET on hemoglobin (it is always there) look at Q17 if you need to review this • In Sickle Cell, there is a mutation and a glutamic acid becomes a Valine • Would the water molecules that are surrounding Hemoglobin ‘want’ to interact with this Valine?

  17. Exit Condition – write out the answers to these questions • Howdoes hemoglobin switches from oxygen-binding (lungs) to oxygen-releasing (muscles)? • What is the role of pH in this shape (conformation) switch? • Howdoes a single nucleotide change causes sickle cell anemia?

  18. Hemoglobinopathies • When bad things happen to nice hemoglobin • http://blc.arizona.edu/courses/181Lab/3D_Files_jsm_S14/Opathies_OXY_Web.html

  19. It happens all the time

  20. Bringing it home • Your semester project will be applying these tools & concepts to the analysis of a genetic disease

  21. Homework Advice to those planning to do well in this course: By task, this is a light week. By concept and skill, it isn’t. Your semester project looks like this week. Next week’s quiz looks like this week. WORK through the Assessor. Revisit Hemoglobin Introduction and Bohr, Babies and Sickle for your next quiz and your next exam.

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