25
The Organic Mechanisms
of the Coenzymes •
Metabolism
1033
N^5 ,N^10 -methylenetetrahydrofolate
Casimir Funk (1884–1967)was
born in Poland, received his medical
degree from the University of Bern,
and became a U.S. citizen in 1920.
In 1923, he returned to Poland to
direct the State Institute of Hygiene.
He returned to the United States
permanently when World War II
broke out.
M
any enzymes cannot catalyze a reaction with-
out the help of a cofactor. Cofactorsassist
enzymes in catalyzing a variety of reactions
that cannot be catalyzed solely by the amino acid side chains
of the protein. Some cofactors are metal ions, while others are
organic molecules.
A metal-ion cofactor acts as a Lewis acid in a variety of ways
to help an enzyme catalyze a reaction. It can coordinate with
groups on the enzyme, causing them to align in a geometry advan-
tageous for reaction; it can help bind the substrate to the active site of the enzyme; it can
form a coordination complex with the substrate to increase its reactivity; or it can in-
crease the nucleophilicity of water at the active site (Section 24.5). An enzyme that has
a tightly bound metal ion ( , ) is called a
metalloenzyme. Carboxypeptidase A is an example of a metalloenzyme (Section 24.9).
PROBLEM 1
How does the metal ion in carboxypeptidase A increase its catalytic activity?
Cofactors that are organic molecules are called coenzymes. Coenzymes are derived
from organic compounds commonly known as vitamins. Table 25.1 lists the vitamins
and their biochemically active coenzyme forms.
A vitaminis a substance the body cannot synthesize that is needed in small
amounts for normal body function. Sir Frederick Hopkins was the first to suggest that
diseases such as rickets and scurvy might result from the absence of substances in the
diet that are needed only in very small quantities. Because the first such compound
recognized to be essential in the diet was an amine, Casimir Funk incorrectly conclud-
ed that all such compounds were amines and called them vitamines (“life-amines”).
The ewas later dropped from the name.
We have seen that enzymes catalyze reactions following the principles of organic
chemistry (Section 24.9). Coenzymes use these same principles. We will see that
Co^2 +,Cu^2 +,Cu^2 + Cu^2 +,Fe^2 +,Mo^2 +,Zn^2 +
