Amino acid composition of polypeptides from influenza virus particles.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to N Baker.
Explore the source record for details and available documents.
We have attempted to estimate the flux of glucose carbon to total body fatty acids and to other metabolic end products in Bar Harbor 129/J mice fasted 5-8 hr. Tracer [U-(14)C]glucose was injected intravenously, and the following data were obtained at various times up to 180 min: plasma glucose C specific activity, plasma glucose concentration, total body glycogen, and (14)C in total body fatty acid, total body lipid, unsaponifiable lipid, expired CO(2), and in hepatic and extrahepatic glycogen. The data were analyzed by three techniques, namely, multicompartmental, semicompartmental, and noncompartmental analyses. All three methods yielded comparable rates of glucose C conversion to total body fatty acids (2-3 micro g of glucose C/min/20 g of body weight). Although the semicompartmental approach is extremely simple (it only requires analyses of plasma glucose specific activity as a function of time and (14)C-labeled fatty acid at one point in time), it gives an apparently valid approximation for the flux of glucose C to fatty acids. Other quantitative aspects of glucose metabolism in postabsorptive mice are also considered.
The flux of glucose carbon to total body fatty acids was measured in unanesthetized mice either after fasting or 50-80 min after they nibbled a small test meal containing 120 mg of glucose (fasted-refed). Flux was calculated from plasma [(14)C]glucose specific activity curves and from total body (14)C-labeled fatty acid 30 min after intravenous injection of tracer [(14)C]glucose. Mobilization of liver glycogen, changes in the body glucose pool size, and total flux of carbon through the glucose pool during periods of fasting and refeeding were defined. Liver glycogen was almost completely depleted 8 hr after food removal. Body glucose pool size fell during fasting and increased after refeeding the test meal. Irreversible disposal rate of glucose C varied directly with body glucose pool size; but flux of glucose C into fatty acids increased exponentially as body glucose concentration increased. Within an hour after nibbling a small test meal, the flux of glucose C into total body fatty acids increased 700% in mice previously starved for 24 hr. However, flux of glucose C into fatty acids in postabsorptive mice (food removed for 2 hr; livers rich in glycogen) was only about 2% of the value calculated from published studies in which the incorporation of an intubated [(14)C]glucose load into total body fatty acid was measured in mice. A possible explanation for this phenomenon is presented.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effect of repeated muscular contraction on the rate of oxidation of the side chain of cholesterol was studied in anesthetized rats. The animals received an intravenous pulse-label injection of either cholesterol-26-(14)C, incorporated into rat plasma lipoproteins, or bicarbonate-(14)C. In half the animals of each group, the hind legs were repeatedly stimulated by electrical impulses. A multicompartmental analysis was attempted, based on the disappearance curve of plasma free cholesterol-(14)C and on the excretion rate of expired (14)CO(2), as well as on previously reported rates of bile acid and adrenal steroid secretion. The rate of expired (14)CO(2) originating from cholesterol-26-(14)C was much less than that predicted by the digital computer analysis; cholesterol degradation could not be evaluated since the data were incompatible with a model that assumes direct oxidation of the side chain to CO(2). A revised model was postulated in which an important fraction of the side chain of cholesterol would be converted to CO(2) only after previous conversion to glucose. Direct measurement of plasma glucose-(14)C after the injection of cholesterol-26-(14)C supported this hypothesis.
Explore the source record for details and available documents.
Many complex problems of lipid metabolism are especially suited for multicompartmental analysis with computers. Examples are presented. The use of a model as a means of communicating one's working hypothesis and the model as it relates to experimental design are discussed. A number of principles relating to experimental design and to the interpretation and presentation of data are illustrated by 12 studies selected from the literature. These include evaluations of turnover and transport rates of liver and plasma triglycerides, triglyceride synthesis, phospholipid synthesis, and lipid oxidation to CO2. A discussion of computer-oriented vs. noncomputer-oriented techniques is included. Some of the practical problems involved in computer analysis are also considered. Among these are the choice of computer, computer applications, stepwise vs. multicompartmental analysis, validity of single-injection type experiments, avoidance of multicompartmental analysis, nonsteady state systems, and nomenclature.
The effect of a single glucose feeding upon the net inflow and outflow transport of plasma free fatty acids (FFA) has been studied in 75 unanesthetized rats. The animals were fasted for 22 +/- 2 hr; then 50 rats were refed 2 ml of 50% glucose by gastric intubation. At 0, 10-15, and 30-35 min after glucose refeeding, the rats were injected with palmitate-1-(14)C complexed to rat serum. The tracer dose included (131)I-labeled albumin. Plasma FFA concentration, (131)I concentration, and FFA-(14)C were measured at five time intervals after injection of the tracer dose. From these data the irreversible disposal rate, or net outflow transport, and the net inflow transport of plasma FFA were calculated. Estimations were based upon a special case of a general solution for measuring net inflow and outflow transport of a circulating metabolite. The general solution is independent of the number of compartments, how they are interconnected, the number of nonradioactive inflows, and where the inflows enter the system. Net inflow = net outflow transport = 7.6 micro eq/min in the fasted state and 3.5 micro eq/min in the new steady state that is reached 30-40 min after glucose refeeding. A very slight imbalance between the rates of net inflow and outflow transport could account for the rapid fall in plasma FFA concentration that results from a single glucose feeding. Theoretical and practical problems associated with studying inflow and outflow transport by means of the technique using a single injection of racer are discussed.
The rate of appearance of (14)CO(2) in expired air after the injection of a single dose of NaH(14)CO(3) has been determined in normal individuals both in the fasted and fed states. These data were combined with previously obtained results on the rate of disappearance of injected palmitate-(14)C from the bloodstream, to give a multicompartmental analysis of free fatty acid oxidation and esterification. The results confirm that glucose feeding promptly inhibits the rate of free fatty acid oxidation to CO(2). The "irreversible disposal rate," or irreversible flux of free fatty acids from the plasma, was also consistently reduced by glucose feeding. The diminution in irreversible disposal, not accounted for entirely by reduction of direct oxidation, must indicate suppression of other disposal mechanisms, including net esterification of free fatty acids. An average drop of 49% in "net esterification" when glucose was given may be compared with the 65% inhibition of rapid free fatty acid oxidation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Plasma triglyceride concentrations were significantly lowered by a single feeding of glucose to rats that had been fasted for 22 hr. Three feedings of glucose produced a similar effect. In the glucose-refed animals mobilization of free fatty acids from adipose tissue was impaired more rapidly than hepatic lipogenesis was restored from its low fasting level. These effects of glucose were shown by both a 50% fall in plasma free fatty acid concentration and an 84% decrease in free fatty acid release by isolated epididymal fat pads within 30 min after a single refeeding of glucose. Hepatic lipogenesis from either acetate-1-(14)C or glucose-U-(14)C was not restored even after glucose had been fed three times at hourly intervals. Triton-induced hypertriglyceridemia was used to measure the hepatic triglyceride secretory rate; it was found that glucose refeeding decreased this rate in all but one of several experiments. This decreased secretion rate was sufficient to account for the nearly complete disappearance of triglyceride in very low density lipoproteins (d < 1.019) that occurred within 1 hr after a single glucose intubation.
Fasted rats injected with actinomycin or fed glucose show increased lipoprotein lipase activity of epididymal adipose tissue. Data from the actinomycin-treated animals showed a direct correlation between the lipoprotein lipase activity and the uptake of lipoprotein triglyceride by the epididymal fat pad in vitro and in vivo. Data from the animals fed glucose confirmed these findings in vitro. These data strongly suggest that lipoprotein lipase plays a major role in triglyceride deposition in adipose tissue.
Palmitate-1-(14)C was injected intravenously into unanesthetized, fasted rats. Disappearance of tracer from plasma free fatty acids was studied. A large component of free fatty acid (FFA) recycling was directly demonstrated by reinjection experiments. The latter studies also indicated the existence of an unidentified, rapidly turning over polar lipid in plasma which was synthesized from palmitate-(14)C. The appearance of (14)C in hepatic and extrahepatic triglycerides, in other esters, and in respired CO(2) was also followed. The data were analyzed using a multicompartmental model and a digital computer. Only a small fraction of the triglycerides formed in liver was derived directly from plasma free fatty acids. The major portion of net triglyceride formation appeared to be by way of an intermediate nontriglyceride ester pool which turned over relatively slowly compared to plasma free fatty acids. Initial approximations are as follows ( micromoles of fatty acid per min per 100 g body weight): net free fatty acid mobilization (irreversible disposal) = 2.4; hepatic triglyceride formation directly from plasma free fatty acid = 0.1; total hepatic lipid formation from plasma free fatty acids = 0.5; oxidation of free fatty acids to CO(2) = 0.8; percentage of respired CO(2) from direct oxidation of fatty acids = 12%; extrahepatic triglyceride formation directly from fatty acids = 0.4; total extrahepatic lipid formed directly from fatty acids = 1.2.
The water-soluble products of the UV-initiated autoxidation of linoleic and linolenic acids emulsified in water were separated into volatile and relatively involatile components, each of which reacted with both thiobarbituric acid (TBA) and peroxidase. The volatile TBA-reactive compound is probably malonaldehyde and the volatile peroxidase-reactive compound is hydrogen peroxide. Additional compounds which absorb UV light were present in the volatile fraction. After thin-layer chromatography of the involatile fraction, reactivity toward TBA and peroxidase was found in the same spot. Approximate molar yields of hydrogen peroxide, malonaldehyde, "hydroperoxides", and other TBA-reactive compounds were estimated. The ratio of "hydroperoxide" to TBA reactivity was lower for linoleic than for linolenic acid. The mass of relatively involatile compounds was about 20 times greater than that predicted from either peroxidase or TBA assays of water extracts of oxidized linolenic acid. The properties of the water extract were similar to those shown by others for the products of prolonged autoxidation (without UV-irradiation) of emulsified methyl linoleate.