Fat metabolism in protein malnutrition

The aim of this work was to make an assessment of the role of impaired lipoprotein secretion from the liver in the pathogenesis of the fatty liver caused by protein malnutrition in infants. The only evidence for this role prior to the study was that serum lipid levels were lower than normal in patients with fatty liver. The proposed method for measuring the incorporation of amino acids into the lipoproteins of children with fatty liver was used first with the rat as a model. It was found, in the development of such a model, that there are great variations in the level of liver fat induced by protein depletion in the rat. The variations depend on the age and nutritional state of the animal at the time of introducing the low-protein diet, and depend on the calorie intake while thay are on the diet. It was found that there were always measurable increases in the liver fat content when 70-gram rats were fed a 6 percent casein diet for 7 to 10 days. The use of this model with either single-injection or constant-infusion techniques showed that the incorporation of labelled amino acids into the serum lipoproteins was reduced. The greatest reduction was in the VLDL fraction of the low-density lipoproteins. There was no evidence for any significant contribution to the fatty liver from increased lipogenesis at the time when the defect in lipoprotein synthesis was apparent. The incorporation of methionine-S35 into the low-density lipoproteins of malnourished children was measured; although the changes were not consistent throughout the group studied, there was some evidence that the incorporation of the amino acid into lipoproteins was less when the children were malnourished than when they had recovered. Some modification in the design of future experiments of this type are discussed. Routine measurements of serum triglycerides in the patients during treatment showed that there are some differences between the pattern seen here and that reported elsewhere. The patients had very low triglyceride levels after recovery. These low levels were found to be due to the high fat content of the diet which the patients received during treatment. The changes in serum triglycerides induced by changing the fat content of the diet were found to be more rapid and to be relatively greater than any changes previously reported for adults. No explanation for this is given at present. The unusual patterns for serum triglycerides found during treatment of the malnourished patients with a low-fat diet appeared at first to be inconsistent with reduced synthesis of lipoprotein being associated with the fatty liver; other changes in fat metabolism concurrent with such a defect, however, could account for the unusual patterns.(AU)

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)

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)

S35 methionine uptake in protein-depleted Jamaican children

There is no reliable test of the severity of protein depletion or indicator as to prognosis. The absence of such a test makes therapeutic trails hazardous and difficult to interpret. In experimentally protein-depleted dogs and in malnourished children, a change from the normal distribution of protein anabolism has been demonstrated by use of radioactive methionine as a tracer. It is suggested that such tracer studies may provide information not otherwise obtainable concerning the essential physiology of protein depletion, and thereby assist in the deveploment and assessment of new methods of treatment (AU)