An accumulation of fatty acids having chain lengths of C22 to C26 was demonstrated in the cholesterol ester fraction of white matter from two boys with adrenoleukodystrophy. A similar accumulation of very long chain fatty acids was also shown in gangliosides and cerebrosides. A disorder of the one-carbon degradation system responsible for the metabolism of some of the very long chain fatty acids may be the basic enzymatic defect in this condition.

Summaryof infants of diabetic mothers) for 20 years, however, the cause is Previous studies have suggested that fetal hyperinsulinemia which occurs in offspring of diabetic mothers is responsible for diminished surfactant production and respiratory distress syndrome. Recognition of specific insulin effects on fetal lung tissue prompted us to characterize insulin receptors on plasma membranes of fetal rabbit lung tissue and to investigate the effects of maternal diabetes on such receptors. Six pairs of pregnant New Zealand rabbits were studied. One of each pair received alloxan (60 mg/kg) intravenously on day 14 of pregnancy, whereas the controls received saline. Animals were sacrificed on day 28 of gestation, and for each experiment, crude plasma membranes were prepared from maternal and pooled fetal lung tissue for '2SI-insulin binding studies. Plasma glucose values were elevated for both maternal diabetic (246 + 81 versus 98.5 + 7.1 mg/dl; P < 0.001) and fetal diabetic offspring (160 + 69 versus 55 2 12 mg/dl; P < 0.02) in comparison to controls. Fetal diabetic offspring had plasma insulin values significantly higher than control fetuses (84.8 + 25 versus 23.2 + 3.7 pU/ml), (mean + S.D.); P < 0.05). Insulin was undetectable in diabetic mothers.Lung membranes from fetuses of diabetic animals bound sipnificaGly more insulin than did those of control fetuses. ~catcharvd analysis yielded curvilinear plots of bound fractions versus total amount of insulin bound suggesting the presence of more than one class of receptors or negative cooperativity. Assuming two classes of receptors, one of high affiity and low capacity and another of low affinity and high capacity, we found that fetal membranes had a five-fold increase in binding capacity of high-affinity receptors as compared to adult membranes. In spite of marked hyperinsulinemia in the offspring of the diabetic animal, the fetal lung, far from experiencing a down-regulation of insulin receptor binding, showed increased insulin binding. This findiig is consistent with observations made previously on circulating monocytes of infants of diabetic mothers.

No abstract

The incorporation of [1-14C]linoleic acid, and [1-14C]linolenic acid into cellular lipids of cultured human skin fibroblasts was studied. Cultured cells took up both labeled fatty acids at nearly the same rate and incorporated them into a variety of lipid classes. At the end of 1 hr incubation with [1-14C]linoleic acid, radioactivity was found in the triacylglycerol (TG) and choline phosphoglyceride (CPG) pools preferentially. Incorporation into the TG fraction decreased rapidly, while the uptake into CPG, serine phosphoglyceride (SPG), and ethanolamine phosphoglyceride (EPG) fractions increased progressively with longer incubation times. Similar results were obtained with [1-14C]linolenic acid as precursor. At the end of 24 hr, desaturation and chain elongation of 18:3 n-3 was more extensive than conversion of 18:2 n-6 to higher polyenoic acids. During pulse-chase experiments with either fatty acid precursor, the incorporated radioactivity was progressively lost from cellular lipids, particularly from the TG and CPG fractions, but continued to increase in the SPG and EPG pools. The similar labeling pattern of cellular phospholipids with linoleic or linolenic acids, and data from pulse-chase studies suggest that a direct transfer of fatty acids from CPG to EPG is a likely pathway in fibroblast cultures. Incorporation into the EPG pool during the pulse-chase experiments paralleled extensive desaturation and elongation of linoleic acid to 20:4 n-6, and 22:4 n-6; and of linolenic acid into 22.5 n-3 and 22:6 n-3.