Biological Reactions
Major concepts
 Biological oxidation reactions are part of energy harvesting pathways; Reducing power is
needed in biosynthetic pathways
 NADH is a biological reducing agent; NAD+ is a biological oxidizing agent
 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
 NADH/NAD+
 Decarboxylation
 Beta decarboxylation vs. alpha decarboxylation vs decarboxylation of amino acids
 Electron sink
Students should be able to:
 Recognize whether a reaction is an oxidation, reduction, or neither
 Know when NADH or NAD+ are likely to be required in a biological reaction
 Draw a basic mechanisms for the interconversion of hydroxyl groups and carbonyls using
NADH/NAD+
 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. Describe these reactions as reduction, oxidation, or neither.
neither
reduction
oxidation
neither
neither
neither
2. Under anaerobic conditions, pyruvate is converted to lactate.
a. What type of reaction is this? reduction
b. What cofactor is needed? NADH
c. Refer to the structures of cofactors to provide a mechanism for this reaction.
H3C
O
O
C
C
cofactor and H+
OH
O
C
H
C
-
O
H3C
O-
3. In the processing of ethanol, it is first converted into acetaldehyde.
a. What type of reaction is this? oxidation
b. What cofactor is needed? NAD+
c. Refer to the structures of cofactors to provide a mechanism for this reaction.
O
cofactor
OH
+ H+
H3C
C
H
4. The following figure contains the citric acid cycle. For each of the starred reactions, describe the
reaction as “oxidation,” “reduction,” or “not redox.” If the reaction is not a redox reaction, how would
you label it using reactions we have learned previously in class?
not redox
isomerization
oxidation
not redox
E+ addition
oxidation
not redox
hydrolysis
5. Provide a non-enzymatic mechanism for this decarboxylation:
6. Label each reaction as “oxidation”, “decarboxylation”, “oxidative decarboxylation” or “none of
these.”
decarbooxylation
oxidative
decarboxylation
oxidation
oxidative
decarboxylation
none of these
7. 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. What is the name of the coenzyme in this series of reactions? PLP
B. How would you describe the reaction in Phase 1? nuc addition (imine formation)
C. Draw mechanism arrows for Phases 2 and 3.
D. If Phase 4 is a hydrolysis, draw the products of this reaction.
8. 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.)
9. During gluconeogenesis, oxaloacetate is decarboxylated.
a. Which carboxy group will be decarboxylated without a coenzyme? the left one
b. Why will the other carboxy group not be decarboxylated? the right one
c. Besides carbon dioxide, what is the other product of the reaction?
O
-
decarboxylation
O
OO
O
CO2 +
10. During the citric acid cycle, isocitrate is converted into -ketoglutarate through a two step process.
a. Label each step with the type of reaction.
OH
-
O
O-
O
O
-
O
O-
O
O
O-
O
+ H+
O
-
O
O
O-
O
oxidation
O
O
H
O
decarboxylation
b. Which coenzyme, if any, is necessary for each step? Why is it necessary?
For step one, NAD+ is needed for the oxidation as a hydride acceptor. For step two, no
coenzyme is needed because it is a -carbonyl carboxylate.
c. Refer to the structures of the coenzymes to provide a mechanism for each step of the
reaction.
d. If the two steps were switched, this process wouldn’t work. Why?
The decarboxylation would not work before the oxidation because the oxidation makes
the -carbonyl carboxylate functional group, which is needed for a spontaneous
decarboxylation.
11. 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.
O
O
H2N
CH
C
OH
H2N
CH
C
OH
H2N
CH2
CH2
CH2
CH2
OH
HN
HN
tryptophan
oxidation
HN
decarboxylation serotonin
-
b. Which coenzyme, if any, is necessary for the second step of this reaction? Why is it
necessary?
PLP is the necessary coenzyme for the decarboxylation because it is not a favorable
reaction.
12. 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
cofactor
O
H
O
Coenzyme A
and another
cofactor
O
SCoA
-
decarboxylation
oxidation
a. Label each step with the type of reaction.
b. Which coenzyme is necessary for each step of this reaction? Why is it necessary?
TPP is the coenzyme necessary for the decarboxylation because it is not a favorable
reaction. NAD+ is the cofactor needed for the oxidation reaction to receive the hydride
formed.
13. As part of the citric acid cycle, a-ketoglutarate must be decarboxylated.
a. What cofactor is necessary? What is its purpose?
TPP is necessary for the decarboxylation in the second step of the mechanism.
b. Fill in arrows in the figure below to complete the mechanism.
O
C
S
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
C
C
R
N
S
R
R
N
S
-OOC
+
R
H
H
14. 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-
*
oxidative
decarboxylation
TPP
O
CoA
H3C
S
*
C
COO-
H2C
COO-
O
aldol
HO
H2C
COO-
C
COO-
H2C
COO-
*
oxidation
H
C
HO
COO-
H2C
H2C
COO-
HC
COO-
C
H
COO-
COO-
electrophilic
addition
*
HO
COO-
oxidative
decarboxylation
TPP
COO-
TPP
*
H
COOC
H2C
C
-OOC
CH2
H
O
oxidation
*
H2C
COO-
H2C
CH2
O
C
COO-
CH2
O-
*
hydrolysis
reaction
O
C
C
*
SCoA
oxidative
decarboxylation
TPP