The glucose/fatty acid cycle and physical exhaustion.

The energy required for sustained exercise is provided by the oxidation of two fuels, glucose and long-chain fatty acids, which are stored as liver and muscle glycogen and adipose tissue triglyceride. The latter provides the largest energy reserve in the body; there is sufficient energy for about five days of continuous marathon running. Glycogen reserves, in contrast, are very limited and, at most, could provide energy for 100 minutes. Evidence is presented of a metabolic limit in the rate of fatty acid utilization, so that sustained exercise at a high power output requires the utilization of both fat and carbohydrate simultaneously. There is a regulatory mechanism by which fatty acid oxidation reduces carbohydrate utilization in muscle--the glucose/fatty acid cycle. This plays an important part in ensuring that marathon runners can continue beyond the theoretical limit of 100 minutes. Triglyceride is mobilized from adipose tissue as long-chain fatty acids and the oxidation of these by muscle reduces the rate of glucose utilization. The availability of fatty acids for oxidation as early as possible in exercise will allow the use of both fuels (fatty acids and glucose) for a longer period of time. Since it appears that fatigue occurs when carbohydrate reserves are depleted, reduction in the rate of glucose utilization by the oxidation of fatty acids is obviously beneficial. The ability of ultra-distance runners to exceed these limits poses interesting metabolic questions relating to exhaustion.