Problem Set 8 with answers

Oxidation of Fatty Acids

The first seven Problem Sets dealt with the fundamental principles you need to predict the products of any biochemical reaction. In Problem Sets 8 to 25, you will use these principles to predict the intermediates in complicated metabolic pathways.
I am having trouble getting the necessary structures into answer for problem 8. Sorry!

Given: Fatty acids with an even number of carbon atoms are oxidized to acetyl-CoA.

1. Predict the intermediates in this pathway.
HINT: “In solving a problem of this sort, the grand thing is to be able to reason backwards. That is a very useful accomplishment, and a very easy one, but people do not practice it much.” Sherlock Holmes (From A Study in Scarlet by A. Conan Doyle)
a. Did you write a balanced equation? (CBM p.192)
b. What does the balanced equation tell you? (CBM p. 192)
c. Did you work backwards as suggested by the world’s greatest detective?
d. What is the justification for working backwards? (rule 6.2, p. 130)
e. Did you use electron pushing to predict the intermediates?
It is very important that you proceed stepwise using the rules of electron pushing established in Chapter 1. If you just write down an intermediate from previous knowledge, you are using memory recall. The purpose of these problem sets is to give you practice in working out reactions logically rather than relying on memory.
f. Did you arrive at diagram 8.12 shown on p. 202 of CBM?
g. Did you recognize the fundamental reaction types occurring in each case?

ANS: (see Fig 8.12)

2. Write two different mechanisms for the initial reaction. From a metabolic point of view, which is the most likely?

a. Did you write the mechanisms shown in Figs. 8.9 and 8.10 of CBM?
b. Did you choose the second mechanism because hydrolysis of PPi pulls the reaction to completion? (see p. 201 of CBM)

3. Look in the databases( and ( to see if you can find the enzyme required for the reactions you have written.
a. Did you find the enzymes shown in Fig. 8.14?
b. Did you confirm your choice for the first reaction?

4. How many ATPs are produced by each turn of the oxidation spiral?
There are two oxidation steps. When you looked up the enzymes, did you find that one uses FAD and the other uses NAD? You know that oxidation of FADH2 by the electron transport system produces 2 ATPs and that oxidation of NADH produces 3 ATPs. Did you conclude that each turn of the cycle produces 5 ATPs?

5. How much energy is produced by oxidation of stearic acid to acetyl-CoA?
a. Stearic acid has 18 carbons. Did you conclude that it takes (18/2) – 1 = 8 turns of the cycle to convert stearic acid to acetyl-CoA?
b. One ATP is used to initiate beta oxidation. Did you conclude that oxidation of stearic acid to acetyl-CoA produces (5 x 8) –1 =39 ATPs?
c. Each ATP is stores 7,300 cal/mol at pH 7 (Table 1, p. 135 of CBM). Did you conclude that oxidation of stearic acid to acetyl-CoA produces 39 x 7,300 = 285,000 cal/mol

6. Fatty acyl dehydrogenase produces the trans isomer. What can you conclude about how the enzyme works?
a. Did you conclude that either two HR’s or two HS’s must be removed by the enzyme?
b. Did you conclude that these hydrogens can be either syn periplanar or anti periplanar so we cannot predict whether the elimination will be syn or anti?

7. Naturally occurring fatty acids are always cis. What problem does that present for oxidation of oleic acid (9-cis-octadecenoic acid)?
Enoyl hydratase (EC requires a trans double bond. The cis double bond produceby three oxidation steps (Fig. 8.20 of CBM) must isomerize to trans.

8. Write two different mechanisms for isomerization of a double bond in a fatty acid.
Which of these mechanisms works in the oxidation of oleic acid? (HINT: Look for the appropriate enzyme(s).
a. Redox:

b. Removal and replacement of an α-hydrogen:

The enzyme, dodecenoyl-CoA Δ3-isomerase (EC catalyzes mechanism “b”.

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