Some aspects of the regulation of fuel supply in omnivorous animals

Abstract

The long-established fact that the degradation of surplus dietary protein takes precedence over the degradation of carbohydrate and fat can be accounted for by a series of regulatory mechanisms. Any surplus carbohydrate and fat is rapidly removed from the circulation by deposition in the form of storage compounds (glycogen and triglyceride). As amino acids cannot be stored in major amounts their concentration in blood and tissue rises, and owing to the high K m value of the enzymes initiating the degradation of the amino acids a rise in their concentration automatically increases the rate of degradation. Another regulatory principle is the adaptive changes in enzyme capacity, which is particularly effective for the essential amino acids. On the one hand, they can cause an accelerated decomposition of surplus amino acids; on the other hand, the enzyme capacity can fall to such low values that the essential amino acids are effectively preserved. The rapid removal of surplus carbohydrate is partly due to glycogen synthesis and partly due to the “glucose fatty acid cycle”. This is not a metabolic cycle but a storage cycle. The section of the cycle leading to the formation of triglyceride from glucose occurs when there is a surplus of carbohydrate, and the release of fatty acid occurs on fasting. The energy loss incurred in the transformation of carbohydrate to triglyceride is less than 7% of the utilizable energy (i.e. of the ATP obtainable). The main direct fuels of tissue oxidation are glucose, fatty acids, ketone bodies, amino acids and lactate. Some tissues (which are listed) depend on glucose as the main fuel; others obtain most of their energy from the oxidation of fatty acids; some can utilize ketone bodies as a major fuel. For many tissues quantitative information on the fuel of respiration is lacking. Relatively little is known about the extent to which amino acids can serve directly as sources of energy in the various tissues. The degradation of the majority of amino acids is initiated by an amino transferase reaction, and systematic measurements of the capacity of various amino transferases in rat tissues, and the variations caused by a high-protein or high-carbohydrate diet, are reported. While the activity of the amino transferases is generally highest in the liver, other organs can also degrade many amino acids rapidly. In the case of the branched-chain amino acids the liver is a minor site. The physiological significance of this phenomenon is discussed. The roles of lactate, ethanol, acetate, and glycerol as fuels of oxidation in various tissues are surveyed, as are the regulatory factors which determine the selection of fuels when a variety of fuels is available.