The turnover of [75 Se] selenomethionine in infants and rats measured in a whole body counter

The gamma-emitting amino acid [75Se]selenomethionine was given to rats and to human infants, and the rate and route of excertion of 75Se was followed for several weeks by daily measurements in a 4 pi whole body counter. These data were used to calculate the turnover rate of total body protein, and the results were checked against other, technically more difficult, methods.(AU)

The measurement of total protein synthesis and catabolism and nitrogen turnover in infants in different nutritional states and receiving different amounts of dietary protein

Total nitrogen turnover and the rates of synthesis and catabolism of total body protein were measured in infants, by means of a constant intragastric infusion of [15N] glycine. Experimental evidence is presented to support the assumption that amino acids from food and from tissue protein catabolism are indiscriminately handled by the body, and that [15N] glycine is a valid tracer for the mixture of total amino-N. N turnover, synthesis and catabolism of protein were all significantly higher in the malnourished as compared to the recovered infant. Net protein synthesis was the same in the two states, and a greater proportion of the N entering the pool was synthesized into protein in the malnourished infant. The rate of total protein synthesis in recovered infants was about 6g per kg body weight per day and was the same in infants receiving a low protein or a high protein intake. However, catabolism was significantly increased and there was greater utilization of N for protein synthesis in infants on a low protein diet. The mechanisms of adaptation to infantile malnutrition and to a low protein diet may be brought about through changes in amount or activity of enzymes concerned with amino acid metabolism. (AU)

Irreversibly sickled erythrocytes: a consequence of the heterogeneous distribution of hemoglobin types in sickle-cell anemia

The amount of fetal hemoglobin (Hb F) in erythrocytes of patients with sickle cell anemia (Hb SS disease) was measured by two methods: (a) photometry of individual cells strained for Hb F by the Kleihauer-Betke technique; and (b) chemical assay of alkali-resistant hemoglobin in cells distributed according to specific gravity by ultracentrifugation. Irreversibly sickled cells (ISC), which could be identified directly during photometry and which were found to gather in high concentration at the bottom of ultracentrifuged cell columns, contained significantly less Hb F than non-ISC. Cell content of total Hb was constant regardless of cell size, shape, or ultracentrifugal behavior: thus absolute amounts of Hb F and S varied reciprocally from cell to cell. In experiments designed to estimate age, at formation, and rate of destruction of ISC, Hb SS blood was incubated with selenomethionine-75Se (which labels reticulocytes) of 51Cr (which labels erythrocytes at random) and reinfused. Sequential blood samples were separated by ultracentrifugation into fractions rich in reticulocytes, non-ISC, ans ISC; and chronological changes in the specific activity of each fraction were determined. Analogous information was obtained from radioautography of sequential blood samples after reinfusion of whole blood labeled with amino acids-3H: this technique permitted direct visual characterization of labeled erythrocytes as ISC of non-ISC, all of which had been reticulocytes at the time of reinfusion. The transformation of non-ISC into ISC, presumably a manifestation of membrane damage, proved to begin soon after cell release from the marrow; and ISC subsequently underwent rapid removal from the circulating blood. It is therefore apparent from these studies that, in Hb SS disease, relatively small reciprocal changes in the amounts of the two major hemoglobins carry predictive importance: (a) net synthesis of Hb F is least in erythroid cells destined to become ISC; and (b) these irreversibly deformed erythrocytes suffer preferential destruction. (AU)

Observations on the mechanisms of adaptation to the low protein intakes

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)