Natural Science Forum / Chemistry / Organic Synthesis / January 2004

Why would one memorize a metabolic chart?  Any question worth asking
retains its value if each victim has a chart to look at.

Back to the organic chem books.  Consider first half of Krebs cycle.
Need to know structure of citric acid (symmetry of citric acid here
helps memory), and that you lose one molecule of CO2 to start.  Now
the organic chem:
1.  Can't easily lose CO2 unless there's a beta-electron sink like a
C=O in the molecule.
2.  Nice to be able to oxidize C-OH to C=O in citric acid, but it's a
tertiary -OH so no oxidation possible.
3.  Can use C=C intermediate to move -OH so it can be oxidized. (This
kind of group transfer is in o. chem I [2-bromo-2-methylbutane
eliminate to 2-methyl-2-butene and HBr/perox. to
2-bromo-3-methylbutane or 2-methyl-2-butanol to 3-methyl-2-butanol
through the alkene with hydroboration-oxidation]). This is
cis-acotinic acid (not usually listed in those charts).
4.  Add the -OH to the C=C making the iso-citric acid.  A secondary
-OH can be oxidized.
5.  If you oxidize one thing, you must reduce something else.  So it
has to be NAD+ -> NADH and not the other way around.
6.  Lose the "middle" -COOH as CO2 as the C=O can now be an electron
sink.

All from O. Chem.