Renal tubular reabsorption rates, reabsorptive maxima, and apparent renal plasma excretory thresholds for carnitine were determined in four children with primary systemic carnitine deficiency (SCD), in two of the mothers of these children, in one patient with muscle carnitine deficiency (MCD), and in seven controls. In SCD the observed values were well below those found in six of seven controls, but one control, a healthy 20-year-old woman with normal muscle carnitine level, also exhibited a renal carnitine leak. In the two mothers of patients with SCD and in the case of MCD some of the parameters of the renal handling of carnitine were slightly altered. Tubular secretion of short-chain acylcarnitines was noted in patients and controls at high plasma free carnitine levels. Augmented excretion of short-chain acylcarnitines occurred at lower plasma free carnitine levels in the patients with SCD than in the other subjects. Free and short-chain acyl-carnitines may compete for the same renal reabsorptive site. A renal defect cannot fully account for primary SCD but may contribute to the carnitine depletion in this disorder.
\s=b\ Cholesterol, triglyceride, and lipoprotein levels were determined in serum from 40 children with diabetes and from controls. Mean cholesterol levels in the children with diabetes (205 \m=+-\ 78 mg/dl) were statistically higher than for controls (155 \m=+-\27 mg/dl), as were mean triglyceride levels (120 \m=+-\63 vs 85 \m=+-\23 mg/ dl). Eight of the children with diabetes had hypercholesterolemia, five had hypertriglyceridemia, and nine had combined hypercholesterolemia and hypertriglyceridemia. Low-density lipoprotein levels were statistically higher and high-density lipoprotein levels statistically lower for children with diabetes compared with control children. Increased urine glucose spillage was found to correlate with higher serum triglyceride levels, suggesting that the elevated triglyceride levels may have been related to diabetes control. With the known association between hyperlipidemia and coronary heart disease (CHD) and between diabetes and CHD, the results of the present study indicate that all children with juvenile diabetes mellitus should have a serum lipid analysis annually.
IN VIVO D-GLUCOSE(1 l), in perfusion studies of the proximal intestine, found rate of absorption of glucose to be about 10 mg/hr/lO cm. In the present study, rate of absorption from a solution with a similar mean glucose concentration was 8 mg/hr/lO cm of the perfused jejunum + ileum.
SUMMARYIn vivo study of D-glucose absorption in small intestine of rats between 7 and 73 days of age suggested that rate of absorption normalized for intestinal weight incre'ased twofold at the time of weaning (21-23 days of age) with no further increase thereafter.
REFERENCES AND NOTES
F a t t y degenerationpropionic acid h y p e r a m m o n e m i a propionic acidemia liver ureagenesis
Effect of Propionic Acid on Fatty Acid Oxidation and Ureagenesis ALLEN M . GLASGOW123' AND H. PETER CHASEUniversit)~ of Colorado Medical Center, B. F. Srolinsky Laborarories, Denver, Colorado, USA
ExtractPropionic acid significantly inhibited 14C0, production from [l-L4C]palmitate at a concentration of 10 in control fibroblasts and 100 p M in methylmalonic fibroblasts. This inhibition was similar to that produced by 4-pentenoic acid. Methylmalonic acid also inhibited "CO, production from [I-"Clpalmitate, but only at a concentration of 1 mM in control cells and 5 mM in methylmalonic cells.Propionic acid (5 m M ) also inhibited ureagenesis in rat liver slices when ammonia was the substrate but not with aspartate and citrulline as substrates. Propionic acid had no direct effect on either carbamyl phosphate synthetase or ornithine transcarbamylase.These findings may explain the fatty degeneration of the liver and the hyperammonemia in propionic and methylmalonic acidemia.
SpeculationIt has been shown that 4-pentenoic acid will produce many of the features of Reye's syndrome in rats. The fact that propionic acid inhibits some of the same reactions as 4-pentenoic acid raises the possibility that other short chain fatty acids less unusual than 4-pentenoic acid could produce the features of Reye's syndrome.Propionic and methylrnalonic acidemias are rare inborn errors of metabolism. These disorders have some of the same features. such as hyperammonemia (15) and fatty degeneration of the liver (8, 11,12). as those of Reye's syndrome. Massive accumulation of a specific short chain is one obvious difference. It has been speculated that short chain fatty acids may be an endogenous toxin in Reye's syndrome (10,16,18). 4-Pentenoic acid will produce hyperammonemia, hypoglycemia, and fatty degeneration of the liver in rats and has been proposed as a possible model for Reye's syndrome (4). We reasoned that perhaps the mechanism of hyperammonemia and fatty degeneration of the liver in propionic acidemia and methylmalonic acidemia was similar to the mechanism in 4-pentenoic acid-treated rats.4-Pentenoic acid is known to inhibit the oxidation of fatty acids and it is thought that this accounts for some of the other features of its toxicity such as the hypoglycemia (15). 4-Pentenoic acid also inhibits ureagenesis, probably at either the step of carbamyl phosphate synthetase or mitochondria1 ornithine uptake (5).Results of the present study show that propionic acid also inhibits fatty acid oxidation and ureagenesis, which may explain the fatty degeneration of the liver and the hyperammonemia often associated with propionic acidemia.
METHODSphosphate-buffered saline, harvested with a brief treatment with trypsin-EDTA, washed twice with phosphate-buffered saline, and then suspended in phosphate-buffered saline (145 m M Na. 4.15 m M K , 140 m M Cl. 9.36 mM PO,, pH 7.4). In most cases the cells were incubated in 3 ml phosphate-buffered sa...
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