Question

1. Cis-aconitate is an intermediate in the citric acid cycle that connects the structure of citrate with isocitrate. It's not always shown explicitly in the scheme for the TCA cycle because it occurs as an intermediate at the active site of the enzyme aconitase: ?? ? cis-aconitate A. Why does aconitase need to convert citrate to isocitrate in the citric acid cycle? In other words, what downstream step is enabled by this isomerization? (Hint: think of the next steps in the cycle) B. An iron sulfur cluster is central to aconitase's activity. Draw the following scenarios. You may draw the iron sulfur cluster simply as "Fe$^{2+}$", the iron center responsible for binding the citrate/isocitrate molecule. Compare the reaction equilibrium describing the deprotonation of i) free H$_2$O versus that of ii) H$_2$O:Fe$^{2+}$. Indicate the relative favorability of products/reactants with the relative size of the equilibrium arrows i) ii) iii) How does the metal cluster activate a water molecule for nucleophilic attack on the cis-aconitate alkene intermediate (hydration)? C. How (generally) might the aconitase enzyme impose selectivity for the cis isomer of aconitate versus its trans isomer? How does this relate to the stereochemical preferences of the aconitase reaction?

          1. Cis-aconitate is an intermediate in the citric acid cycle that connects the structure of citrate with isocitrate.
It's not always shown explicitly in the scheme for the TCA cycle because it occurs as an intermediate at the
active site of the enzyme aconitase:
??
?
cis-aconitate
A. Why does aconitase need to convert citrate to isocitrate in the citric acid cycle? In other words, what
downstream step is enabled by this isomerization? (Hint: think of the next steps in the cycle)
B. An iron sulfur cluster is central to aconitase's activity. Draw the following scenarios. You may draw the iron
sulfur cluster simply as "Fe$^{2+}$", the iron center responsible for binding the citrate/isocitrate molecule.
Compare the reaction equilibrium describing the deprotonation of i) free H$_2$O versus that of ii) H$_2$O:Fe$^{2+}$.
Indicate the relative favorability of products/reactants with the relative size of the equilibrium arrows
i)
ii)
iii) How does the metal cluster activate a water molecule for nucleophilic attack on the cis-aconitate alkene
intermediate (hydration)?
C. How (generally) might the aconitase enzyme impose selectivity for the cis isomer of aconitate versus its
trans isomer? How does this relate to the stereochemical preferences of the aconitase reaction?

1. Cis-aconitate is an intermediate in the citric acid cycle that connects the structure of citrate with isocitrate.
It's not always shown explicitly in the scheme for the TCA cycle because it occurs as an intermediate at the
active site of the enzyme aconitase:
??
?
cis-aconitate
A. Why does aconitase need to convert citrate to isocitrate in the citric acid cycle? In other words, what
downstream step is enabled by this isomerization? (Hint: think of the next steps in the cycle)
B. An iron sulfur cluster is central to aconitase's activity. Draw the following scenarios. You may draw the iron
sulfur cluster simply as "Fe^2+", the iron center responsible for binding the citrate/isocitrate molecule.
Compare the reaction equilibrium describing the deprotonation of i) free H2O versus that of ii) H2O:Fe^2+.
Indicate the relative favorability of products/reactants with the relative size of the equilibrium arrows
i)
ii)
iii) How does the metal cluster activate a water molecule for nucleophilic attack on the cis-aconitate alkene
intermediate (hydration)?
C. How (generally) might the aconitase enzyme impose selectivity for the cis isomer of aconitate versus its
trans isomer? How does this relate to the stereochemical preferences of the aconitase reaction?

Added by Jes-S T.

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