The utilization of glucose, palmitate, and oleate for the synthesis of lung lipids was studied in isolated rat lungs. Lungs were ventilated with 5% CO2 in air and perfused for 100 min with a Krebs-Ringer bicarbonate buffer (pH 7.4), containing 3% fatty acid-free albumin and either 5.6 mM [U-14C]glucose or 0.25 mM [1-14C]palmitate, or 0.25 mM [1-14C]-oleate. At the end of 100 min of perfusion with these precursors, between 73 and 85% of total lipid 14C was recovered as phospholipid. Glucose carbon was mainly incorporated into triglyceride fatty acids (TG-FA) and phosphatidylcholine fatty acids (PC-FA) of 16- and 18-carbon chain length. After perfusion with [14C]palmitate and [14C]oleate, only 65 and 20% of 14C was recovered as PC 16-carbon and 18-carbon FA, respectively. The remaining 14C was mainly recovered as FA shorter than the 14C precursors. Schmidt degradation analysis of lipid FA demonstrated considerable labeling of alkyl carbons on perfusion with the carboxyl-labeled precursors, indicating that FA degradation products were used for synthesis of lipid FA. This process was enhanced on addition of glucose to the perfusate.
During feeding experiments with [omega-14C]oleic acid and [omega-14c]nervonic acid to adult rats, 14C-labelled C26, C28 and C30 fatty acids were recovered from the intestinal mucosa, liver, plasma, kidney and stools. The structures of these fatty acids were determined by g.l.c., radio-g.l.c. and mass spectrometry. The Schmidt and Ginger degradation methods indicated that most of the 14C found in these extra-long fatty acids remained in the omega position. These radioactive extra-long fatty acids were found mainly in the polar lipids of rats killed 3 or 15 h after being fed on labelled oleic acid or nervonic acid. Rats killed 63 h later yielded only traces of these extra-long fatty acids. When the rats were given antibiotics or received the same radioactive fatty acids by intravenous injection, the labelled extra-long fatty acids could not be detected in any of the tissues. We conclude that they were probably synthesized by elongation of oleic acid and nervonic acid by intestinal micro-organisms (probably yeasts) and then absorbed by the intestinal mucosa.
Abstract The rate of 14 CO 2 production from 2‐ 14 C‐5‐FU was measured in rats bearing the Novikoff ascites hepatoma. Tracer amounts were injected and 14 CO 2 collected over a 6‐hour period. As the tumor cells proliferated the rate of 2‐ 14 C‐5‐FU oxidation decreased markedly over the approximately 12± 2 days between implantation of tumor cells and death. On the day of innoculation of tumor cells, oxidation proceeded nearly linearly until almost 50% of the injected 2‐ 14 C‐5‐FU was converted to 14 CO 2 in about 4 hours. With time after tumor innoculation, the rate of 14 CO 2 collection declined; ten days after innoculation only about 27% was oxidized by 4 hours, and at the terminal stage it declined to about 18% over 4 hours. Calculated from the time curves, the time oxidation of 25% of the injected trace dose increased from 88± 27 min to 195± 42 min after ten days, to 300 ± 59 min at the moribund state after 12 ± 2 days. Similar decreases in oxidation rate of 5‐FU were observed during growth of a solid implanted mammary carcinoma and for two other 2‐ 14 C‐labelled pyrimidines, uracil and thymine injected in trace quantities. By comparing cancer subjects with themselves at different time‐intervals from the onset of the disease and treatment, it might be possible to guage treatment dosages in the progress of the disease.
THE POSSIBLE RELATIONSHIP of hypercholesteremia to atherosclerosis had led to consideration of thyroxine as a useful agent in lowering serum cholesterol.1,3Since the dose of L-thyroxine required for this purpose usually produces hypermetabolic effects,3many analogues of thyroxine have been tested in an attempt to find one with a predominantly cholesterol-lowering action.4,5This study was undertaken to determine the effect of oral dextrothyroxine (D-T4) on the metabolism of intravenously administered C14-labeled cholesterol and tripalmitin.
Materials and Methods
Twenty-two euthyroid male patients with high serum cholesterol levels, various arteriosclerotic disorders, or both were studied. No changes were made in any patient's program other than addition of the drug. The biological half-life of C14-labeled cholesterol and tripalmitin in serum was determined for each patient for 30 days before and after the administration of 8 mg. of D-T4daily. Respiratory quotient, oxygen uptake,
