PROBLEM SET 13-Oxidative Deamination of Amino Acids

In 1828, Friedrich Wöhler,  synthesized urea by heating silver isocyanate and ammonium chloride:
AgNCO + NH4Cl = (NH2)2CO (urea) + AgCl

Wöhler wrote to the famous Swedish Chemist, Jon Jacob Berzelius, “I must tell you that I can make urea without the use of kidneys, either man or dog.”

This was the first time a compound containing carbon, hydrogen and nitrogen had been synthesized outside a living organism. Wöhler’s synthesis is considered the start of Organic Chemistry.  What Wöhler didn’t know is that the liver (not the kidneys) requires 16 reactions to synthesize urea from  amino acids.

In most cases, catabolism of amino acids starts with removal of the amino group as ammonia. Ammonia is toxic. Organisms that live in the water simply excrete the ammonia. Land based critters excrete either uric acid (birds) or urea (most animals). In this Problem Set we will deal with the biosynthesis of urea. This is one of the most complicated metabolic pathways in biochemistry. Using chemical logic and three facts, you can construct a detailed map for the biosynthesis of urea starting with the oxidative deamination an amino acid.

1. Write the general structure for an α-amino acid.

2. Using generic coenzymes, write two different mechanisms for oxidative deamination of an amino acid.

3. Pyridoxal phosphate (PALP) is required for removal of α-amino groups. Show how PALP works.


4. Pyridoxamine (PAMP) is formed by oxidative deamination. How is PALP regenerated?

5. Glutamic acid plays a key role in transamination. Show how this works.

6. How many ATPs are produced by transamination?

a. Urea is formed from arginine, which acts catalytically.
b. One of urea’s nitrogens comes from ammonia. The other comes from aspartic  acid, which acts catalytically.
c. Four ATPs are required for the synthesis of urea.

Construct a metabolic map for the synthesis of urea.

8. Show how the urea cycle ties into an intermediate of the Citric Acid Cycle to produce the”Urea Bicycle”.

9. Show how an amino acid is oxidized by the urea bicycle.

10. Look up the enzymes that are predicted by your map. Add these enzymes to your map.

11. Write an overall equation for oxidative deamination of any amino acid. What conclusions can you draw? (HINT: Write 16 coupled reactions).

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