Monday's Molecule #220

Last week's molecule was 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) [Monday's Molecule #219]. Jean-Marc lives in Switzerland so I've made arrangements to fly over there to visit him and treat him to fondue at the Pinte de Pierre-à-Bot in Neuchatel.

Today's molecule is one of those molecules that students should never be asked to memorize. It's an intermediate in a very important pathway. Identify the molecule and the pathway. You have to give me the full name and the common abbreviation. Email your answer to me at: Monday's Molecule #220. 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: This week's molecule is 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU). It is an intermediate in the degradation pathway from uric acid (or urate) to carbon dioxide and ammonia. Uric acid is the main breakdown product in purine catabolism. Humans have lost activity of all of the enzymes of this pathway so they excrete urate. Most other species excrete ammonia, although in other animals some of the terminal enzymes have been lost. Some textbooks do not show the uric acid degradation pathway since it doesn't occur in humans and those textbooks aren't interested in an evolutionary approach to biochemistry (e.g. Berg, Tymoczko, and Stryer). The other majors textbooks (Voet & Voet, Garrett & Grisham, Nelson & Cox [Lehinger]) all show uric acid converted directly to allantoin via urate oxidase. This reaction was shown to be incorrect about 15 years ago. The actual pathway from uric acid to allantoin involves two intermediates; 5-hydroxyisourate and OHCU.

Image Credit: Moran, L.A., Horton, H.R., Scrimgeour, K.G., and Perry, M.D. (2012) Principles of Biochemistry 5th ed., Pearson Education Inc. page 568 [Pearson: Principles of Biochemistry 5/E] © 2012 Pearson Education Inc.

The winner, for the second week in a row, is Jean-Marc Neuhaus.

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
Oct. 21: Jean-Marc Neuhaus

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