Organic Chemistry

828 CHAPTER 19 Carbonyl Compounds III

The first step in the biosynthesis of a fatty acid is a Claisen condensation between a

molecule of acetyl thioester and a molecule of malonyl thioester. You have seen that, in

the laboratory the nucleophile needed for a Claisen condensation is obtained by using

a strong base to remove an Strong bases are not available for biological

reactions because they take place at neutral pH. So the required nucleophile is gener-

ated by removing —rather than a proton—from the of malonyl thioester.

(Recall that 3-oxocarboxylic acids are easily decarboxylated; Section 19.17.) Loss of

also serves to drive the condensation reaction to completion. The product of the

condensation reaction undergoes a reduction, a dehydration, and a second reduction to

give a four-carbon thioester.

The four-carbon thioester undergoes a Claisen condensation with another molecule

of malonyl thioester. Again, the product of the condensation reaction undergoes a re-

duction, a dehydration, and a second reduction, this time to form a six-carbon

thioester. The sequence of reactions is repeated, and each time two more carbons are

added to the chain. This mechanism explains why naturally occurring fatty acids are

unbranched and generally contain an even number of carbons.

Once a thioester with the appropriate number of carbon atoms is obtained, it undergoes

a transesterification reaction with glycerol in order to form fats, oils, and phospholipids

(Sections 26.3 and 26.4).

PROBLEM 41

Palmitic acid (hexadecanoic acid) is a saturated 16-carbon fatty acid. How many moles of

malonyl-CoA are required for the synthesis of one mole of palmitic acid?

PROBLEM 42

a. If the biosynthesis of palmitic acid were carried out with and nondeuterated

malonyl thioester, how many deuteriums would be incorporated into palmitic acid?

b. If the biosynthesis of palmitic acid were carried out with and nondeuter-

ated acetyl thioester, how many deuteriums would be incorporated into palmitic acid?

A Biological Decarboxylation

An example of a decarboxylation that occurs in biological systems is the decarboxylation

of acetoacetate. Acetoacetate decarboxylase, the enzyme that catalyzes the reaction, first

forms an imine with acetoacetate. The imine is protonated under physiological conditions

• OOCCD
  2 COSR

CD 3 COSR

CO 2

CO 2 a-carbon

a-hydrogen.

reduction dehydration

reduction

O

CH 3 CSR

O

SR+ CO 2

SR CH 3 CSRCH 2 C

O

−

O −

O C CH 2 C

O O

CH 3 CSRCH 2 C

O

O

CH 3 CH CH 2 C SR

O OH

CH 3 CH 2 CH 2 CSR CH 3 CH CHC SR

O

CH 3 CH 2 CH 2 C SR +

O

CH 3 CH 2 CH 2 CH 2 CH 2 C SR

O

CH 3 CH 2 CH 2 C CH 2 CSR

OO

SR

OO

−O C CH 2 C

Claisen

condensation

1. reduction


2. dehydration


3. reduction