Effect of Severe Burn Injury on Substrate Cycling by Glucose and Fatty Acids

Increases in metabolic rate and core temperature are common responses to severe injury. We have investigated the hypothesis that these responses are due to increases in substrate cycling. A substrate cycle exists when opposing, nonequilibrium reactions catalyzed by different enzymes are operating simultaneously. At least one of the reactions must involve the hydrolysis of ATP. Thus, a substrate cycle both liberates heat and increases energy expenditure, yet there is no net conversion of substrate to product. In studies in volunteers (n = 18) and in patients with severe burns who were in a hypermetabolic state (n = 18), we used stable-isotope tracers to quantify substrate cycling in the pathways of glycolysis and gluconeogenesis and a cycle involving the simultaneous breakdown and synthesis of stored triglyceride (triglyceride–fatty acid cycle). The total rates of triglyceride–fatty acid and glycolytic–gluconeogenic cycling were elevated in the patients by 450 and 250 percent, respectively (P<0.01). An infusion of propranolol in the patients greatly reduced triglyceride–fatty acid cycling but did not affect gluconeogenic–glycolytic cycling. We conclude that increased substrate cycling contributes to the increased thermogenesis and energy expenditure following severe burns and that the increased triglyceride–fatty acid cycling is due to beta-adrenergic stimulation. (N Engl J Med 1987; 317:403–8.), THE existence of substrate cycles was proposed approximately 20 years ago.¹ A substrate cycle may exist when opposing, nonequilibrium reactions catalyzed by different enzymes are active simultaneously. One example of a substrate cycle is the simultaneous breakdown (lipolysis) and resynthesis (reesterification) of triglycerides (triglyceride–fatty acid cycling). Potential substrate cycles also exist in the processes of glycolysis and gluconeogenesis. One such cycle involves the conversion of glucose to glucose-6-phosphate and back to glucose (glucose cycle); another involves the conversion of fructose-1-phosphate to fructose 1,6-diphosphate and back to fructose-1-phosphate (fructose cycle). Substrate cycling involves the use of high-energy phosphate bonds in ATP,…