Monday, October 14, 2013

Monday's Molecule #219

Last week's molecule was cobalamin or vitamin B12. The structure was solved by Dorothy Crowfoot Hodgkin who won the Nobel Prize in Chemistry in 1964. There have been ten Nobel Prizes for work on vitamins and coenzymes. There were a lot of people who got this one right. The winner is Piotr Gasiorowski. The undergraduate winner is Jacob Toth [Monday's Molecule #218]. That makes four lunches that I owe Jacob. Right now, he's far away (British Columbia) but he may be coming to Toronto to collect. That may cut down on his chances of winning!

Today's molecule is a very common enzyme found in all species (I don't know of any exceptions). It's part of a pathway that's familiar to all biochemistry students. The figure illustrates a classic "induced fit" mechanism of substrate binding where the binding of one substrate creates the binding pocket for the second substrate. In this case, it's the homodimeric animal version of the enzyme showing rotation of the small domain of one of the subunits. Name the enzyme and the reaction it catalyzes.

There's more. In order to win a free lunch you have to explain something else. It's related to the fundamental concepts that all biochemistry students should know. The standard Gibbs free energy change for the reaction catalyzed by this enzyme is ΔG°′ = -31.5 kJ mol-1. What does that mean if you are trying to understand the reaction that takes place inside the cell? Is there a reason why this reaction isn't coupled to synthesis of ATP? I'm interested in seeing how most Sandwalk readers understand the fundamental concept of reaction thermodynamics.

Email your answers to me at: Monday's Molecule #219. I'll hold off posting your answers for at least 24 hours. The first one with the correct answer wins. I will only post the names of people with mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your email message.)

Some past winners are from distant lands so their chances of taking up my offer of a free lunch are slim. (That's why I can afford to do this!)

In order to win you must post your correct name. Anonymous and pseudoanonymous commenters can't win the free lunch.

Winners will have to contact me by email to arrange a lunch date. Please try and beat the regular winners. Most of them live far away and I'll never get to take them to lunch. This makes me sad.

Comments are now open.

UPDATE: The molecule is citrate synthase, one of many enzymes that show considerable amounts of structural change during binding. It looks like the "induced fit" mechanism is a general feature of substrate binding and not something that is limited to just a few examples. That part of the question was easy but the second part was hard. Jean-Marc Neuhaus is this week's winner because he has a copy of my book and was able to look up the explanation. The important point to keep in mind when you are thinking about the thermodynamics of biochemical reactions is that most reactions are near-equilibrium reactions where ΔG = 0. In the case of the citrate synthase reaction, ΔG°′ = -31.5 kJ mol-1, in the direction of citrate formation. What this means is that the equilibrium concentrations of the products are very much higher than the concentrations of the substrates. These concentrations would be closer to being equal if the reaction was coupled to substrate level phosphorylation (e.g. ATP formation). This would be a problem since the concentration of oxaloacetate (substrate) inside the cell is very low. (Because the standard free energy change of the malate dehydrogenase reaction is ΔG°′ = +30 kJ mol-1).

Winners
Nov. 2009: Jason Oakley, Alex Ling
Oct. 17: Bill Chaney, Roger Fan
Oct. 24: DK
Oct. 31: Joseph C. Somody
Nov. 7: Jason Oakley
Nov. 15: Thomas Ferraro, Vipulan Vigneswaran
Nov. 21: Vipulan Vigneswaran (honorary mention to Raul A. Félix de Sousa)
Nov. 28: Philip Rodger
Dec. 5: 凌嘉誠 (Alex Ling)
Dec. 12: Bill Chaney
Dec. 19: Joseph C. Somody
Jan. 9: Dima Klenchin
Jan. 23: David Schuller
Jan. 30: Peter Monaghan
Feb. 7: Thomas Ferraro, Charles Motraghi
Feb. 13: Joseph C. Somody
March 5: Albi Celaj
March 12: Bill Chaney, Raul A. Félix de Sousa
March 19: no winner
March 26: John Runnels, Raul A. Félix de Sousa
April 2: Sean Ridout
April 9: no winner
April 16: Raul A. Félix de Sousa
April 23: Dima Klenchin, Deena Allan
April 30: Sean Ridout
May 7: Matt McFarlane
May 14: no winner
May 21: no winner
May 29: Mike Hamilton, Dmitri Tchigvintsev
June 4: Bill Chaney, Matt McFarlane
June 18: Raul A. Félix de Sousa
June 25: Raul A. Félix de Sousa
July 2: Raul A. Félix de Sousa
July 16: Sean Ridout, William Grecia
July 23: Raul A. Félix de Sousa
July 30: Bill Chaney and Raul A. Félix de Sousa
Aug. 7: Raul A. Félix de Sousa
Aug. 13: Matt McFarlane
Aug. 20: Stephen Spiro
Aug. 27: Raul A. Félix de Sousa
Sept. 3: Matt McFarlane
Sept. 10: Matt Talarico
Sept. 17: no winner
Sept. 24: Mikkel Rasmussen
Oct. 1: John Runnels
Oct. 8: Raúl Mancera
Oct. 15: Raul A. Félix de Sousa
Oct. 22: Mikkel Rasmussen
Nov. 12: Seth Kasowitz, Bill Gunn
Nov. 19: Michael Rasmussen
Dec. 4: Paul Clapham, Jacob Toth
Dec. 10: Jacob Toth
Dec. 17: Bill Chaney, Dima Klenchin, Bill Gunn
Jan. 14: Evey Salara
Jan. 21: Piotr Gasiorowski
March 11: Bill Gunn, River Jiang
March 18: Bill Gunn
April 8: Michael Florea
April 15: no winner
April 29: Anders Ernberg
May 6: Alex Ling, Michael Florea
May 13: Bill Chaney
June 24: Michael Florea
July 2: Matt McFarlane
July 8: no winner
July 15: Rosie Redfield, Thuc Quyen Huynh
July 22: Jacob Toth
July 29: Alex Ling, Matt McFarlane
August 5: Brian Shewchuk
Sept. 2: no winner
Sept. 9: Bill Chaney
Sept. 16: Zhimeng Yu
Sept. 23: Mark Sturtevant, Jacob Toth
Sept. 30: Susan Heaphy
Oct. 7: Piotr Gasiorowski, Jacob Troth
Oct. 14: Jean-Marc Neuhaus


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