PROBLEM SET 14-Oxidation of Amino Acid Carbons-1


In the next few chapters, we are going to examine the reactions of various amino acids. This is the part of Biochemistry that many students hate. They hate it because they have to memorize memorize metabolic maps for 20 different amino acids, and many of the maps are quite complicated. Of course, you do not have to do that.  From the structures and  a few additional facts, you can predict the pathways that lead to complete oxidation. You can also predict whether or not a particular amino acid is glucogenic or ketogenic or both. These Problem Sets deal primarily with catabolic pathways. However, you should consider biosynthetic pathways for the  non-essential amino acids (Ala, Asp, Asn, Glu, Gln and Pro are non-essential).

Because amino acids have more than one functional group, several reactions are often possible. This complicates the task of choosing the correct reactions for a particular metabolic pathway. When it is feasible, you should start by writing down all the possibilities. This often reveals some interesting biochemistry. Sometimes, you can use biochemical logic to solve the problem. Usually, you will have to look for the appropriate enzymes in order to make the choice between alternatives.

Here are some useful generalizations.
1. Although decaboxylation often occurs as a first step, it is not really part of catabolism, Therefore, we will ignore it in these reactions even though, in some cases, they produce important products (amines).
2. Transamination is usually the first step in amino acid catabolism. There are some exceptions, which we will point out at the appropriate time, but this is usually a good place to start.
3. Transamination gives an α-keto acid, which you know can be decarboxylated to an aldehyde in the presence of thiamine pyrophosphate. The aldehyde can be oxidized to an acid. This often occurs in bacteria and yeast. Most of the time, in the presence of TTP, lipoamide, FAD and NAD, animal cells convert an α-ketoacid  to its acyl-CoA derivative.   You do not have to write a mechanism. You can check out the assumption when you look for the appropriate enzyme, but sometimes the specific enzyme has not been reported even though we are pretty sure the reaction occurs.

In this Problem Set, we will consider six amino acids: alanine, aspartic acid, asparagine, glutamic acid, glutamine, proline. The structures of these amino acids are:

1. Write reactions for hydrolysis of asparagine and glutamine.
2. Write reactions for the conversion of proline to glutamic acid.
3. Write a balanced reaction for the conversion of proline to glutamic acid. Does this agree with the reactions you wrote?
4. Write the products for transamination of alanine, glutamic acid and aspartic acid.
5. Show how Ala, Asp, Asn, Glu, Gln and Pro are oxidized to carbon dioxide and water.
6. Which of these amino acids are glucogenic? Explain.
7. What special role does glutamate dehydrogenase play in the catabolism of these amino acids?
8. How many ATPs are generated by oxidation of any one of these amino acids to carbon dioxide and water.
9. Explain what is meant by an “essential amino acid”.
10. Are any of these amino acids essential? Explain by writing pathways.
11. Conversion of glutamic acid to proline presents some special problems.  Look up the enzymes and discuss your findings.
12. Construct a metabolic map that summarizes the metabolism of Ala, Asp, Asn, Glu, Gln and Pro

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