Observations on the mechanisms of adaptation to the low protein intakes

ABSTRACT

Experiments are described which attempt to throw light on the mechanism by which animals and man can adapt to low protein intakes. In the rat, studies by constant infusion of labelled amino acid have shown that in the protein depleted animal there is a small reduction in the total protein turnover this, however, is not enough to account for the great reduction in urinary nitrogen output. Constant infusion and single injection experiments agree in showing that in rats on a low protein diet there is a change in the pattern of protein turnover synthesis of carcass protein (muscle and skin) is reduced, while that of liver protein is well maintained. The preservation of synthesis in liver seems to depend partly on increased re-utilization of amino acids liberated by the catabolism of tissue protein. This economy may be brought about by adaptive enzyme changes -decreased activity of the urea cycle enzymes and increased activity of amino acid activating enzymes in the liver. These changes, previously described by others in the rat have been shown to occur in the human liver also. Studies in human infant with 75selenium-labelled methionine provide some support for the concept that when the protein intake is limited, turnover is preferentially maintained in the liver. However, not all liver-produced proteins behave in the same way; studies of albumin kinetics in infants show that when the protein intake is altered, there is a rapid change in the rate of albumine synthesis, together with a redistribution of albumin between intra and extravascular spaces. Later and more slowly occurs a change, presumably compensatory, in the rate of albumin catabolism. Hormonal changes may play a part in these adjustments. Increased cortisone and decreased insulin activity would have the effect of promoting amini acid uptake at the expense of muscle. It is concluded that the net nitrogen loss which occurs when the protein intake is reduced results simply from the time-lag before the adaptive mechanisms come into play, and therefore cannot logically be regarded as the loss of reserve protein. The practical implications of this concept are discussed (Summary)