Download Decarboxylation Reactions Major concepts Decarboxylation

Decarboxylation Reactions
Major concepts
 Decarboxylation reactions result when a carboxylic acid (or carboxylate) decompose to give
carbon dioxide. They can occur under acidic or basic conditions.
 Decarboxylation reactions are not redox reactions, but are often linked to oxidation reactions.
 When a carboxylate is “Beta” to a carbonyl, spontaneous decarboxylation can result and
requires no cofactor.
 When a carboxylate is “Alpha” to a carbonyl, decarboxylation requries a cofactor called
Thiamine pyrophosphate (TPP) to stabilize the intermediates in the reaction (electron sink.)
 When a carboxylate is “alpha” to an amine (i.e. “amino acid”), decarboxylation requires
pyridoxal phosphate (PLP) as a cofactor to stabilize the intermediates in the reaction (electron
sink.)
Vocabulary
 Decarboxylation
 Beta decarboxylation vs. alpha decarboxylation vs decarboxylation of amino acids
 Electron sink
Students should be able to:
 Draw a mechanism for Beta-decarboxylation under basic conditions
 Determine when a decarboxylation requires a cofactor and when it does not.
 Recognize an oxidative decarboxylation, and explain why the oxidation was linked to
decarboxylation.
Daily Problems
1. Provide a non-enzymatic mechanism for this decarboxylation:
O
O
heat
O-
H2O
O
+ CO2
2. Label each reaction as “oxidation”, “decarboxylation”, “oxidative decarboxylation” or “none of
these.”
3. Refer to the following figure to answer the questions below:
O
NH3+
HO
H
HO
OPi
+
HO
-O
N
H
O
Phase 1
HO
N
OPi
-O
HO
O
HO
NH
CO2
Phase 2:
HO
N
OPi
HO
H+
HO
NH
Phase 3
HO
N
OPi
Phase 4
H
HO
HO
NH
A.
B.
C.
D.
What is the name of the coenzyme in this series of reactions?
How would you describe the reaction in Phase 1?
Draw mechanism arrows for Phases 2 and 3.
If Phase 4 is a hydrolysis, draw the products of this reaction.
4. In the process below, pyruvic acid is converted to acetaldehyde. In the mechanism provided, all
intermediates are given. Fill in the missing mechanism arrows for all four steps. (Note: An enzyme
provides the proton necessary for step 3.
O
O
S
O-
O-
-
C
O
R
+
S
N
C
R
O
R
N
R
O
-
O
-
O
H
S
H
S
+
H+
C
S
C
R
R
C
N
R
N
R
R
N
R
5. During gluconeogenesis, oxaloacetate is decarboxylated.
a. Which carboxy group will be decarboxylated without a coenzyme?
b. Why will the other carboxy group not be decarboxylated?
c. Besides carbon dioxide, what is the other product of the reaction?
O
-
decarboxylation
O
OO
O
CO2 +
6. During the citric acid cycle, isocitrate is converted into -ketoglutarate through a two step process.
a. Label each step with the type of reaction.
b. Which coenzyme, if any, is necessary for each step? Why is it necessary?
c. Refer to the structures of the coenzymes to provide a mechanism for each step of the
reaction.
a. If the two steps were switched, this process wouldn’t work. Why?
OH
-
O
-
O
O
O
-
O
O-
O
O
O
-
O
+ H+
O
-
O
-
O
O
O
H
O
O-
O
7. The following reaction is part of the process by which tryptophan is converted to serotonin, a
neurotransmitter.
a. Label each step with the type of reaction.
b. Which coenzyme, if any, is necessary for the second step of this reaction? Why is it
necessary?
O
O
H2N
CH
C
OH
H2N
CH
C
OH
H2N
CH2
CH2
CH2
CH2
OH
HN
tryptophan
HN
HN
serotonin
8. Pyruvate dehydrogenase is an enzyme that converts pyruvate to acetyl CoA through a series of
chemical reactions. Although this is a simplified scheme, the pathway generally follows this path:
O
O
Coenzyme A
and another
cofactor
O
cofactor
H
O
SCoA
O-
a. Label each step with the type of reaction.
b. Which coenzyme is necessary for each step of this reaction? Why is it necessary?
9. As part of the citric acid cycle, a-ketoglutarate must be decarboxylated.
a. What cofactor is necessary? What is its purpose?
b. Fill in arrows in the figure below to complete the mechanism.
O
S
C
R
O-OOC
N
+
R
O
O
-
O
-
O
-
O
S
C
S
C
R
-OOC
N
R
-OOC
R
N
R
H+
O
-
O
-OOC
H
H
S
-OOC
+
C
R
N
S
C
R
R
N
R
10. The following figure contains the citric acid cycle. A. Label one reaction as an “aldol reaction,” one
reaction as an “electrophilic addition,” and one reaction as a “hydrolysis reaction.” B. Label all reactions
in which CO2 is produced. If a cofactor is required, give the cofactor. C. Label all reactions that are
oxidations.
O
O
H3C
O-
*
O
CoA
H3C
S
*
C
COO-
H2C
COO-
O
HO
H2C
COO-
C
COO-
H2C
COO-
*
H
C
HO
COO-
H2C
H2C
COO-
HC
COO-
C
H
COO-
COO-
HO
*
*
H
COOC
H2C
COO-
C
-OOC
CH2
H
O
*
H2C
COO-
H2C
CH2
O
C
COO-
CH2
O-
*
O
C
*
SCoA
C
COO-