In this Problem Set, we will encounter oxidase reactions. The term oxidase is used to indicate a  reaction in which molecular oxygen is the acceptor. However, there are there are two classes of enzymes, oxidases and oygenases,  that involve a direct reaction between molecular oxygen and a substrate.  Oxygenases catalyze reactions in which at least one of the oxygen atom from molecular oxygen is incorporated into the product. As the name suggests, monooxygenases catalyze reactions in which one oxygen atom is incorporated into the product. Dioxygenases catalyze reactions in which both oxygen atoms are incorportated into the product. Neither oxygen is incorporated into the product in oxidase reactions. We discussed cytochrome oxidase, which uses electrons from the electron transport system to reduce oxygen to water (Chapter 7). However, many oxidase reactions involve a direct reaction between oxygen and a substrate. We need a mechanism(s) that will enable us to predict the products of these reactions.

We considered the structure of oxygen in Chapter 7. You might want to review that material. Molecular oxygen exists as a diradical in its ground state so we concluded that it is set up for free radical reactions. Insertion between a carbon and a hydrogen to give a hydroperoxide followed by elimination of hydrogen peroxide is one of the most common mechanisms.

Let us apply this to an amino acid:

In some cases, it is possible for the imino acid to cyclize before being released from the enzyme.

Here are a two more examples of oxidase reactions involving a direct reaction of molecular oxygen with the substrate.. Glucose oxidase (EC catalyzes the reaction between glucose and oxygen. Oxygen reacts at C1. We can write:

The mechanism involves insertion of molecular oxygen between C1 and H1 to form an enzyme bound hydroperoxide. Elimination produces hydrogen peroxide and gluconolacone.

Pyruvate oxidase(CoA acetylating) (EC uses molecular oxygen and CoA. Let us predict the products:

In this reaction, elimination of hydrogen peroxide must be set up by addition of a nucleophile. There are actually two pyruvate oxidases.The enzyme,  EC,  uses CoA to set up the elimination. This enzyme gives acetyl-CoA, carbon dioxide and hydrogen peroxide. The other enzyme, EC, uses Pi. It gives acetyl-phosphate, carbon dioxide and hydrogen peroxide.  Notice that this is an alternative mechanism for oxidative decarboxylation of an a-amino acid. However, these reactions are confined to bacteria, Animal cells use pyruvate dehydrogenase, which we know requires TPP, lipoamide, FAD and NAD. Never-the-less, we should keep this mechanism in mind when looking for enzymes that catalyzed oxidative decarboxylation of alpha-amino acids.





1. Without any further information, construct a tentative map for catabolism of lysine.

2. What can you predict?

3. Write three mechanisms for removal of the alpha-amino group and predict the products.

4. Which of these reactions actually occur?

5. Write three different mechanisms for removal of the 6-amino group of lysine .

6. Lysine 6-transaminase (EC is found in yeast and bacteria, but not in animal cells. Never-the-less, animal cells do carry out transamination of the 6-amino group. The reaction requires 2-oxoglutarate, but not PALP. Write two mechanisms that show how this might occur.

7. NADH acts catalytically in transamination of the 6-amino group of lysine. Using a generic redox agent, write a mechanism that predicts he products.

8. Revise your original map to reflect the information you obtained from the databases and the conclusions you drew from that information. Include enzymes and coenzymes.








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