Robert Scheig

Hepatic metabolism of 1-14C octanoic and 1-14C palmitic acids

The hepatic metabolism of 1−14C octanoic acid was compared with that of 1−14C palmitic acid in male rats which were fed. After intraportal injection only 1/6 to 1/18 as much octanoic acid as palmitic acid was incorporated into hepatic lipids. In contrast, octanoic acid yielded two to four times as much water-soluble product as did palmitic acid. Similar, but even more impressive, differences between the incorporation of these fatty acids into hepatic lipids were observed in liver slices incubated with14C octanoate and14C palmitate. The oxidation of octanoate to CO2 was more than 10 times as great as that of palmitate. With both substrates, triglycerides comprised almost half the labeled lipid recovered. However octanoate yielded a higher proportion of labeled, unesterified fatty acids and a lower proportion of labeled phospholipid and monoglycerides than did palmitate. Most of the14C recovered in hepatic lipids after incubation with 1−14C octanoate was found in the carboxyl groups of long-chain fatty acids, suggesting that the latter had been synthesized from 2-carbon fragments formed from the oxidation of octanoate. In contrast, only a small fraction of the palmitate was elongated.The similarities and differences between the metabolism of octanoic and palmitic acid in liver and intestine, and the possible nutritional significance of octanoic acid are discussed.

Gas chromatography of the trimethylsilyl derivatives of iodotyrosines and iodothyronines

Abstract Gas chromatographic analysis of the trimethylsilyl derivatives of the iodotyrosines, iodothyronines, tyrosine, and thyronine is described. The silylated derivatives can be synthesized within 5 min at 50° using N,O -bis (trimethylsilyl) acetamide and are readily resolved within 30 min by temperature-programmed gas chromatography. Possible biological applications of this separation technique are discussed.

Inhibition of Postheparin Lipolytic Activity in Uremia and its Relationship to Hypertriglyceridemia

Summary The pathogenesis of hypertriglyceridemia associated with renal failure was studied in 10 non-nephrotic uremic patients undergoing twice-weekly hemodialysis. Fasting plasma triglyceride levels, lipoprotein electrophoretic patterns, and postheparin lipolytic activity (PHLA), using both Ediol and rat chylomicrons as substrate, were determined in each patient. Although PHLA activity was reduced in all patients, serum triglyceride levels were elevated to over 190 mg/100 ml in only six. Plasma from the 10 uremic patients usually inhibited PHLA from normal subjects, but often the degree of inhibition was small and did not correlate with the degree of impairment of PHLA. These results suggest that reduced PHLA may be related in part to a circulating plasma inhibitor, but that factors other than plasma clearance of triglyceride are more important in the development of the hyperlipemia seen in chronic uremia.

Studies on the separation of pyridine nucleotides by thin-layer chromatography.

Abstract Thin-layer chromatography has evolved as an analytical method having several advantages over separations using paper chromatography. The main advantages are speed of analysis and ease of recovery of the sample from the supporting media. The present report describes a thinlayer chromatographic method for the separation of oxidized and reduced diphosphopyridine and triphosphopyridine nucleotides together with data concerning the stability of these compounds under the conditions of tissue extraction procedures.

Effects of l-asparagine and related compounds on the hepatic fatty infiltration and necrosis induced by ethionine and carbon tetrachloride

Abstract 1. In rats given ethionine or carbon tetrachloride, intraperitoneal injection of l -asparagjne fully protected against fatty infiltration of the liver. l -Asparagine did not prevent CCl 4 -induced hepatic necrosis. l -Glutamine and l -methionine also prevented fatty infiiltration after ethionine or CCl 4 , but l -aspartic and α-ketoglutaric acids did not. 2. Chromatographic analysis of the hepatic lipids after CCl 4 administration revealed that the intraperitoneal injection of l -asparagine had prevented the expected alterations in the fatty acid pattern indicative of lipid mobilization from adipose tissue. 3. The implications of these findings are discussed.

Effects of ethanol on lipid metabolism in adipose tissue.

Abstract 1. 1. Ethanol, in vitro , but not its metabolic products acetaldehyde and acetate, diminished glyceride-glycerol formation from glucose in lipocytes from rat epididymal fat pads by 29%. Ethanol had no effect on either the rate of fatty acid synthesis from glucose or the type of fatty acids synthesized. 2. 2. Ethanol was oxidized to CO 2 by lipocytes and was utilized for fatty acid synthesis and complex lipid formation. About 85% of the lipids formed were triglycerides. All the label from [I- 14 C]ethanol was in the fatty acid moieties of complex lipids and none in glyceride-glycerol. Most of the fatty acids formed were saturated, but 32% were C 16–22 unsaturated fatty acids. Ethanol was presumably first oxidized to acetate, since the lipids formed from [I- 14 C]acetate were the same as those formed from ethanol. 3. 3. Acetaldehyde was produced from ethanol by homogenates of adipose tissue. More acetaldehyde was formed at pH 9.6 than at pH 7.4. Nevertheless, no alcohol dehydrogenase activity was detected in either cell sap or whole homogenates of adipose tissue. 4. 4. An ethanol oxidizing system was demonstrated in the particulate fractions of adipose tissue sedimenting at 10000 × g and 105000 × g which required oxygen and a NADPH generating system. Optimum activity of the particles occurred at pH 7.4 and none at pH 9.6, but significant activity was observed at pH 9.6 when whole homogenates were the enzyme source. 5. 5. It is concluded that ethanol may affect lipid metabolism in adipose tissue by suppressing glyceride-glycerol formation and by being utilized as a substrate for fatty acid synthesis.

Fatty livers, adenosine triphosphate and asparagine

Abstract The effects of l -asparagine on the levels of triglyceride and adenosine triphosphate (ATP) in rat liver after the administration of ethionine, CCl 4 or ethanol have been investigated. The results indicate that L-asparagine prevents the decrease in hepatic ATP produced by each of these agents and protects against the fatty infiltration of the liver that follows the administration of ethionine or small doses of CCl 4 , but not against that produced by large doses of CCl 4 or ethanol. These observations suggest that hepatic ATP depletion may not play a key role in the pathogenesis of the fatty liver produced by these agents.

Protection by orotic acid against the renal necrosis and fatty liver of choline deficiency.

Summary Addition of 1% orotic acid to a choline-deficient diet lowered the incidence of hemorrhagic renal necrosis in young rats from 86% to 41%, and within 24 hr prevented the accumulation of hepatic triglycerides by almost 50%. Simultaneous supplementation of the diet with 0.25% adenine sulfate did not influence these protective effects of orotic acid in choline deficiency.

Observations on lipids of the alimentary canal of the hagfish Eptatretus stoutii.

Abstract 1. 1. The hagfish liver, bile and small intestine are rich in lipids. These sources are low in 18 : 2 fatty acids and high in the 16 : 1 fractions, as compared with human intestine. 2. 2. It is uncertain as yet whether the lipid-rich hagfish intestine represents a physiologic counterpart of the human disorder β-lipoprotein deficiency. 3. 3. Some properties of hagfish bile are described. Chromatographically there is no appreciable free taurine or glycine.