Biochemistry 102 PROBLEM SET #6 Paul Price 2005
Oxidation of Fatty Acids
1. Energy in Triacylglycerols. On a per-carbon basis, where does the largest amount of biologically
available energy in triacylglycerols reside: in th e fatty acid portions or the glycerol portion?
Indicate how knowledge of the chemical structure of triacylglycerols provides the answer.
2. The Chemistry of the Acyl-CoA Synthetase R eaction. Fatty acids are converted into their
coenzyme A esters by the reversible reaction catalyzed by acyl-CoA synthetase:
R–CO 2-+ ATP + CoA R(CO)CoA + AMP + PP i
(a) The enzyme-bound intermediate in this reacti on has been identified as the mixed anhydride of
the fatty acid and adenosine monophosphate (AMP), acyl-AMP:
Write two equations corresponding to the two steps involved in the reaction catalyzed by acyl-CoA
(b) The reaction above is readily reversible, with an equilibrium constant near 1. How can this
reaction be made to favor formation of fatty acyl-CoA? (see problem 6 in set 2)
3. The first three steps of β oxidation chemically resemble three successive steps of the citric acid
cycle. Which steps are these?
4. Oxidation of Tritiated Palmitate. Palmitate uniformly labeled with tritium ( H) to a specific activity
of 2.48 x 10 8 counts per minute (cpm) per micromole of palmitate is added to a mitochondrial
preparation that oxidizes it to acetyl-CoA. The acet yl-CoA is isolated and hydrolyzed to acetate.
The specific activity of the isolated acetate is 1.00 x 10 7 cpm per micromole. Is this result,
consistent with the β-oxidation pathway? Explain. What is the final fate of the removed tritium?
5. Compartmentationin β Oxidation. Free palmitate is activated to its coenzyme A derivative
14almitoyl-CoA) in the cytosol before it can be oxidized in the mitochondrion. If palmitate and
[ C]coenzyme A are added to a liver homogenate, palmitoyl-CoA isolated from the cytosolic
fraction is radioactive, but that isolated from the mitochondrial fraction is not. Explain.
6. Effect of Carnitine Deficiency. A patient de veloped a condition characterized by progressive
muscular weakness and aching muscle cramps. These symptoms were aggravated by fasting,
exercise, and a high-fat diet. The homogenate of a muscle specimen from the patient oxidized
added oleate more slowly than did control hom ogenates of muscle specimens from healthy
individuals. When carnitine was added to the pa tient's muscle homogenate, the rate of oleate
oxidation equaled that in the control homogenates. The patient was diagnosed as having a carnitine
(a) Why did added carnitine increase the rate of oleate oxidation in the patient's muscle
(b) Why were the symptoms aggravated by fasting, exercise, and a high-fat diet?
7. Consequences of a High-Fat Diet with No Car bohydrates. Suppose you had to subsist on a diet of
whale and seal blubber with little or no carbohydrate.
(a) What would be the effect of carbohydrate deprivation on the utilization of fats for energy?
(b) If your diet were totally devoid of carbohydrate, would it be better to consume odd- or even-
numbered fatty acids? Explain. 14
8. Palmitic acid labeled with C in carbon atom 9 is oxidized under co14itions in
which the citric acid cycle is operating. What will the location of C be in (a)
acetyl-CoA, (b) oxaloacetate? Assume only one turn of the citric acid cycle.
9. Certain branched-chain fatty acids such as pristanic acid can undergo β oxidation. (a)
How many cycles of β oxidation are required to complete ly degrade this fatty acid?
(b) How many C (acetyl CoA), C (propionyl CoA), and C (methylpropionyl CoA)
2 3 4
products are formed?
10. What is the exact nu mber of NADH and FADH produced by the following
(a) The complete oxidation of β-hydroxybutyrate to CO in t2e mitochondrial
matrix of a heart muscle cell.
(b) The complete oxidation of palmitate to CO in a skeletal muscle cell.
(c) The complete oxidation of linolenic acid (CH CH3[CH 2 CH
CH 2 3CH ) 2 6H) 2o CO in a 2keletal muscle cell.
(d) The generation of 4 molecules of acetoacetate from palmitoyl CoA in the matrix
of a liver mitochondria.
ANSWERS TO PROBLEM SET #6
1. Most of the energy (ATP) produced in catabolism is derived from the electron
pairs in NADH and FADH 2. In general, one C-C or C-H bond contains the high
potential electron pair to produce one NADH or FADH . Electrons in C-O, N-H,
O-H, and C-N bonds do not have sufficient potential energy to produce NADH or
FADH . 2he fatty acid portion, which is mainly -CH 2- groups, clearly has a
higher density per C of high potential C-C an