Metabolism of Fatty Acids and Glucose
To the Editor:
Apstein and Taegtmeyer1 note that increased glycolytic substrate from glucose-insulin-potassium treatment has been shown to improve outcome in acute ischemic conditions and that this treatment attenuates the ischemia-induced decrease in ATP. One mechanism for this improvement should be due to the fact that in the metabolism of glucose, energy stored in the high-energy phosphate bonds requires relatively less oxygen than does an equivalent energy storage from metabolism of fatty acids. For example, oxidation of 1 mol of glucose yields a net gain of 38 high-energy phosphate bonds1 while utilizing 6 mol of O2, or 6.3 high-energy phosphate bonds per mole of O2. Metabolism of the fatty acid palmitate, on the other hand, yields 129 high-energy phosphate bonds2 while utilizing 31 mol of O2, or 4.1 high-energy phosphate bonds per mole of O2. Therefore, for each mole of O2 consumed, there is a 53.7% higher energy production in the form of high-energy phosphate bonds from the metabolism of glucose than from the metabolism of palmitate.
Nevertheless, each gram of palmitate produces significantly more high-energy bonds than a gram of glucose, and the caloric value of the stored high-energy phosphate bonds derived from the oxidation of a gram of palmitate is 2.4 times greater than that derived from a gram of glucose, albeit at a greater relative cost in oxygen. Hence, when oxygen is abundant and food is scarce, there is an advantage in utilizing fatty acids for fuel as opposed to using glucose. The reverse, however, would occur when food is plentiful and oxygen is scarce.
The above indicates that for the heart to work efficiently, it must be able to switch rapidly from the metabolism of fatty acids to the metabolism of glucose. Evidence shows that this indeed occurs and that with increased epinephrine,3 as in stress, or with hypoxia,4 the heart switches from fatty acid metabolism to glucose metabolism. Increasing the concentration of glucose and insulin would facilitate this switch5 and in so doing would decrease an ischemic burden. The decreased ability to make this switch could help explain the more devastating effects of ischemia in patients with diabetes mellitus and/or insulin resistance.
- Copyright © 1998 by American Heart Association
Apstein CS, Taegtmeyer H. Glucose-insulin-potassium in acute myocardial infarction: the time has come for a large, prospective trial. Circulation. 1997;96:1074–1077.
Harper HA. Review of Physiological Chemistry. Los Altos, Calif: Lange Medical Publications; 1967.
Collins-Nakai RL, Noseworthy D, Lopaschuk GD. Epinephrine increases ATP production in hearts by preferentially increasing glucose metabolism. Am J Physiol. 1994;267(pt 2):H1862-H1871.
Carlson MG, Snead WL, Hill JO, Nurjihan N, Campbell PJ. Glucose regulation of lipid metabolism in humans. Am J Physiol. 1991;261(pt 1):E815–E820.
We appreciate the interest of Drs Kessler and Goldman in our editorial and agree that glucose oxidation yields more ATP per mole of O2 than palmitate oxidation. However, according to Opie,R1 there is a 12% greater yield of ATP per mole of O2 from glucose oxidation relative to palmitate, not 53.7% as Drs Kessler and Goldman suggest.
Opie LH. The Heart. 2nd ed. New York, NY: Raven Press; 1991:211, 238.