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Alcohol consumption and its relation to cardiovascular risk factors in Germany.

OBJECTIVE: To analyse the association of alcohol consumption and blood lipids, haemostatic factors, and homocysteine in German adults by gender and age groups. DESIGN: Cross-sectional population-based survey. SETTING: Data from the German National Health Interview and Examination Survey 1998, representative for age, gender, community size, and federal state. SUBJECTS: From a sample of 7124 Germans between 18 and 79 y old, 2420 women and 2365 men were selected. Only individuals who were not currently receiving medical treatment or did not have disorders related to cardiovascular disease were selected for this study. RESULTS: Using analyses of variance, mean blood levels of total cholesterol, HDL cholesterol, HDL/total cholesterol ratio, total glycerides, fibrinogen, antithrombin III, and homocysteine adjusted for age, socioeconomic status, East/West Germany residence, body mass index, tobacco use, sports activity, and coffee consumption, if appropriate are presented by alcohol consumption groups (0, >0-10, >10-20, >20-30 and >30 g/day). The HDL/total cholesterol ratio increased with higher alcohol groups up to 10-20 g/day (+15%) for women and >30 g/day (+18%) for men, showing the strongest rise among men aged 55-79 y. Fibrinogen decreased with higher alcohol groups up to 10-20 g/day for women and 20-30 g/day for men. Among women, homocysteine levels showed a U-shaped curve with a minimum of 8.49 mmol/l at 10-20 g alcohol/day (-8%, reference: nondrinking), whereas an inverse association was observed for men. CONCLUSIONS: Moderate alcohol consumption is associated with favourable levels of several cardiovascular risk factors. The most favourable cardiovascular risk factor profile among women was observed among those drinking 10-20 g alcohol/day. Beneficial effects seem to be more pronounced among older men.

Adult↗

Decreased lipolysis and enhanced glycerol and glucose utilization by adipose tissue prior to development of obesity in monosodium glutamate (MSG) treated-rats.

OBJECTIVE: To determine the metabolic alterations that lead to the neonatal administration of monosodium glutamate (MSG), which results in arrested growth and obesity. ANIMALS AND DESIGN: Wistar rats were injected 5 times, every other day, with 4 g of MSG/kg b.w. or with hyperosmotic saline (controls), within the first 10 days of life, and were studied at the age of 30 days. RESULTS: Body weight was lower, whereas adipocyte lipid content, cell diameter, surface area and volume were higher in MSG rats than in controls. Plasma glucose, insulin, NEFA, glycerol and triglyceride levels, and in vitro production of NEFA by lumbar fat pad pieces incubated under basal conditions or in the presence of epinephrine and epinephrine plus glucose in the media were lower in MSG than in control rats. In the same fat pad pieces, the conversion of 1-14C-glycerol into fatty acids was always enhanced and its conversion into glyceride glycerol was enhanced when incubations were carried out in the presence of epinephrine or glucose. Both the hormone sensitive lipase activity and mRNA expression were lower in adipose tissue from MSG rats. Besides, the number of insulin receptors, lipid synthesis from U14C glucose, 3H-2-deoxy D-glucose uptake and cellular GLUT4 translocation index were higher in adipocytes from MSG rats than from the controls. CONCLUSION: It is proposed that an enhanced insulin sensitivity in 1 month old MSG rats is responsible for the decreased lipolytic activity and enhanced glucose uptake. In addition, the enhanced lipogenesis and glycerol reutilization seen in their adipose tissue, disturbs the normal balance between fat depots breakdown and accumulation in favor of the latter.

Adipose Tissue↗

Not all brands are created equal: a comparison of selected components of different brands of Serenoa repens extract.

Recommendations regarding the use of plant-derived medications for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) state that every brand should be fully evaluated and considered separately. Disparity between a number of brands in terms of their stated and actual doses has been recently highlighted. The aim of this study was to fully quantify the variation in Serenoa repens extracts (SrE) commercially available for the treatment of BPH-associated LUTS. To this end, 14 brands of SrE were compared. Concentrations of free fatty acids (FFAs), methyl and ethyl esters, long-chain esters and glycerides were assessed using liquid and gas chromatography. Many of the brands showed a significantly different proportional content which may have an impact on their clinical efficacy and safety. The high concentrations of FFAs in particular, which previous research has suggested as comprising the active agent of SrE for the treatment of LUTS, may influence the clinical benefit derived from each product. Our findings lend further weight to recommendations by the 5th International Consultation on BPH that plant-derived treatments should be analysed and considered as independent entities despite their common origin. Only extracts with demonstrated pharmacological activities and proven clinical efficacy should be considered for the treatment of patients with BPH.

Humans↗

Intestinal metabolism of fatty acids.

1. The effect of concentration on the oxidation and incorporation into lipids of lauric acid and linoleic acid by rings of rat small intestine has been studied in vitro. 2. In the absence of glucose, the oxidation of lauric acid in the range 0.01-5.0mm showed a maximum at 0.1mm. In the presence of glucose the maximum was at 0.5mm. The oxidation of linoleic acid in the presence of glucose increased throughout the concentration range 0.01-5.0mm. 3. The incorporation of lauric acid into lipids was maximal at 0.5-0.6mm in the presence of glucose, but at 10mm in the absence of glucose. At 0.8mm-lauric acid, in the presence of glucose, over 75% of the incorporated lauric acid was in triglycerides, but at 10mm they only contained 30%. The incorporation of glucose carbon into glycerides paralleled the incorporation of lauric acid. 4. In the range 0.01-2.5mm-linoleic acid the quantity incorporated into lipids increased. In the range 0.01-0.4mm linoleic acid was incorporated predominantly into triglycerides, but between 0.4 and 1.0mm most was in diglycerides, and between 2.5 and 5.0mm most was in monoglycerides. 5. The relationship of fatty acid concentration to the mechanism of absorption is discussed, together with the correlation between the distribution of the absorbed fatty acids within the tissue lipids and the lipase activity of intestinal mucosa.

Animals↗

Estimation of the pentose cycle in the perfused cow's udder.

1. The distributions of (14)C have been compared in the glucose and galactose moieties of lactose obtained from cows' udders perfused with blood containing [1-(14)C]-, [2-(14)C]- and [6-(14)C]-glucose. The (14)C of the glucose moiety was found in the same position as that of the administered glucose, but in the galactose moiety the (14)C from [2-(14)C]glucose was extensively randomized into positions 1 and 3. It is concluded that the glucose moiety arose from free glucose and the galactose moiety from hexose phosphate intermediates and that the latter reflected the randomization occurring through reactions of the pentose cycle. 2. The proportion of the glucose metabolized via the pentose cycle for those cells making lactose was estimated from the distribution of (14)C in the galactose moiety and found to be about 23% in one experiment and 30% in another experiment. 3. The yield and distribution of (14)C were determined in the glycerol of fat from the tissue in experiments with [2-(14)C]- and [6-(14)C]-glucose. There was a greater randomization of (14)C in the glycerol than in C-1, C-2 and C-3 of the galactose moiety of lactose. The ratio of the yield of (14)C in the glycerol from [2-(14)C]glucose to that of [6-(14)C]glucose was very low and from this ratio it was calculated that less than 10% of the glucose was metabolized by the Embden-Meyerhof pathway and approx. 60-70% was converted into lactose. 4. [6-(14)C]Glucose and [6-(3)H]glucose were used to determine whether the (3)H at the C-6 position remained stable during its conversion into glyceride of fat from the tissue. Twenty-seven per cent of the (3)H was labilized during this conversion. Therefore it was not possible to use [2-(14)C]glucose and [6-(3)H]glucose in a single experiment to measure the relative conversion of the C-2 and C-6 positions of glucose to glycerol.

Animals↗

The incorporation of [1-14C] acetate into the methyl ketones that occur in steam-distillates of bovine milk fat.

1. The (14)C-labelling of the fatty acids and the methyl ketones in steam-distillates of milk fat from a lactating cow that had been injected intravenously with [1-(14)C]acetate was determined. 2. The labelling patterns of the C(6)-C(16) fatty acids and the corresponding methyl ketones with one fewer carbon atoms were similar, particularly so for the C(5)-C(10) compounds at 9 and 22hr. after the injection of [1-(14)C]acetate. The isolation of (14)C-labelled methyl ketones in the range C(3)-C(15) is evidence that the beta-oxo acid precursors, which are glyceride-bound in the milk fat, are synthesized in the mammary gland from acetate. The absence of heptadecan-2-one in steam-distillates and the extremely low specific radioactivity of stearic acid are further evidence for this biosynthetic pathway. 3. The specific radioactivities of the C(5)-C(15) methyl ketones were higher (with the exception of C(9) methyl ketone in the second milking) than the specific activities of the corresponding fatty acids with one more carbon atom. This is consistent with the methyl ketone precursors' being formed during the biosynthesis of fatty acids rather than being products of beta-oxidation of fatty acids.

Acetates↗

Stdies on lipogenesis in vivo. Effects of starvation andre-feeding, and studies on cholesterol synthesis.

1. Studies in vivo have been carried out on hepatic and extrahepatic cholesterol synthesis and also on the effects of starvation and re-feeding on both cholesterol and fatty acid synthesis. 2. In rats and mice fed on a stock diet, extrahepatic tissues accounted for about 4 times as much newly synthesized cholesterol as did the liver. The liver appeared to be somewhat more important in the rat than the mouse. Feeding with cholesterol greatly decreased and cholestyramine greatly increased hepatic cholesterol synthesis without much effect on extrahepatic synthesis. 3. Mice starved for up to 7hr. did not lose any of the ability to convert a [U-(14)C]glucose meal into fat, whereas 18hr. of starvation resulted in an 80% loss of fatty acid synthesis in liver and carcass, an 80% loss in liver cholesterol synthesis and a 65% decrease in carcass cholesterol synthesis; 18hr. of food deprivation also decreased the proportion of counts in epididymal fat pads present as fat and increased the proportion present as glyceride glycerol. 4. Re-feeding for up to 7hr. restored fatty acid synthesis from a [U-(14)C]glucose meal to about 50% of the values for non-starved mice but had no effect on hepatic cholesterol synthesis. The altered distribution of counts in the epididymal fat pads caused by starvation was restored to normal after feeding for 1hr.

Acetates↗

Effects of insulin-induced hypoglycaemia on the fate of glucose carbon atoms in the mouse.

1. [U-(14)C]Glucose was injected into mice and the distribution of (14)C in various chemical fractions of the whole body was determined at times from 15min. to 8hr. after injection. 2. At 1hr. after injection 31.8% of the recovered (14)C was found in the expired air and 26.7% was found in the isolated glycogen, lipids, proteins, nucleic acids and in other acid-insoluble carbon compounds (;residual (14)C'). The rest (41.5%) was combined in acid-soluble substances. 3. When insulin was injected 5min. or 1hr. before injection of [U-(14)C]glucose, and the mouse was killed 1hr. later, the (14)C content of expired air, glycogen, protein and ;residual (14)C' was not significantly affected; but the incorporation of (14)C into lipids was increased two- to three-fold. 4. Chromatography of the lipids on silicic acid columns and by thin-layer chromatography showed that the main effect of insulin injection was to increase the incorporation of (14)C into fatty acids. 5. A significant increase of (14)C after insulin injection was also found in a glyceride in which the (14)C was combined in glycerol.

Animals↗

Lipid composition of human serum lipoproteins.

1. The lipid compositions of the low-density lipoproteins, the high-density lipoproteins and the ultracentrifugal residue of human serum are presented, with emphasis on certain lipoprotein classes and lipid components not previously described. 2. Except for the lipoproteins with the lowest and highest densities, there is a trend for stepwise successive increase or, respectively, decrease in the relative amounts of the main constituents of lipoproteins. 3. High-density lipoprotein-2 and high-density lipoprotein-3 have different amounts of certain lipids; high-density lipoprotein-2 has relatively more free cholesterol and sphingomyelin; high-density lipoprotein-3 has more free fatty acids, diglycerides and ceramide monohexosides. 4. All the lipoproteins contain hydrocarbons of the alkane series. The greatest amount, which averages 4.4% of total lipid extracted, is in the ultracentrifugal residue; n-alkanes comprise 18-50% of the hydrocarbons. 5. All the lipoproteins contain ceramide monohexosides. The highest relative contents of these glycolipids are in high-density lipoprotein-3 and in the ultracentrifugal residue. 6. The ultracentrifugal residue contains 55% of the total quantity of free fatty acids present in serum. The remaining free fatty acids are distributed among the other lipoprotein classes. 7. The choline-containing phospholipids (phosphatidylcholine, lysophosphatidylcholine and sphingomyelin) comprise about 90% of the phospholipids in all the lipoprotein classes except the low-density lipoprotein-2, which contains about 80% of these phospholipids. 8. The presence of a large amount of lysophosphatidylcholine in the ultracentrifugal residue and the successive decrease of sphingomyelin from the low-density lipoprotein-1 to the ultracentrifugal residue was confirmed. 9. The low-density lipoprotein-2 and the ultracentrifugal residue are characterized by relatively high contents of the lower glycerides.

Adult↗

Interrelationships between fatty acid biosynthesis and acyl-lipid synthesis in Chlorella vulgaris.

1. Fatty acid synthesis from [2-(14)C]acetate by Chlorella vulgaris cells grown and incubated in the dark is limited almost entirely to the production of saturated and monoenoic acids. 2. In light-incubated cells, both saturated and polyunsaturated fatty acids are rapidly synthesized. 3. Two groups of lipids can be distinguished in both dark- and light-incubated cells. The first group, consisting of phosphatidyl-glycerol, monogalactosyl diglyceride, lecithin and neutral glyceride, has a very high turnover rate for certain fatty acids. The second group, consisting of digalactosyl diglyceride, sulpholipid, phosphatidylethanolamine and phosphatidylinositol, has a slow turnover of fatty acids. 4. The lipids with rapid fatty acid turnover may be involved in the sequences of saturated and unsaturated fatty acid synthesis. A classification of lipids is made on the basis of their suggested functions.

Acetates↗

The control of fatty acid and triglyceride synthesis in rat epididymal adipose tissue. Roles of coenzyme A derivatives, citrate and L-glycerol 3-phosphate.

1. Methods are described for the extraction and assay of acetyl-CoA and of total acid-soluble and total acid-insoluble CoA derivatives in rat epididymal adipose tissue. 2. The concentration ranges of the CoA derivatives in fat pads incubated in vitro under various conditions were: total acid-soluble CoA, 0.20-0.59mm; total acid-insoluble CoA, 0.08-0.23mm; acetyl-CoA, 0.03-0.14mm. 3. An investigation was made of some postulated mechanisms of control of fatty acid and triglyceride synthesis in rat epididymal fat pads incubated in vitro. The concentrations of intermediates of possible regulatory significance were measured at various rates of fatty acid and triglyceride synthesis produced by the addition to the incubation medium (Krebs bicarbonate buffer containing glucose) of insulin, adrenaline, albumin, palmitate or acetate. 4. The whole-tissue concentrations of glucose 6-phosphate, l-glycerol 3-phosphate, citrate, acetyl-CoA, total acid-soluble CoA and total acid-insoluble CoA were assayed after 30 or 60min. incubation. The rates of fatty acid and triglyceride synthesis, calculated from the incorporation of [U-(14)C]glucose into fatty acids and glyceride glycerol respectively, and the rates of glucose uptake, lactate plus pyruvate output and glycerol output were measured over a 60min. incubation. 5. The rate of triglyceride synthesis could not be correlated with the concentrations of either l-glycerol 3-phosphate or long-chain fatty acyl-CoA (measured as total acid-insoluble CoA). Factor(s) other than the whole-tissue concentrations of these recognized precursors appear to be involved in the determination of the rate of triglyceride synthesis. 6. No relationship was found between the rate of fatty acid synthesis and the whole-tissue concentrations of the intermediates, citrate or acetyl-CoA, or with the two proposed effectors of acetyl-CoA carboxylase, citrate (as activator) or long-chain fatty acyl-CoA (as inhibitor). The control of fatty acid synthesis appears to reside in additional or alternative factors.

Acetates↗

Glucose metabolism in the superovulated rat ovary in vitro. Effects of luteinizing hormone and the role of glucose metabolism in steroidogenesis.

1. Superovulated rat ovary slices from rats treated with 20mug. of luteininzing hormone/100g. body wt. 2hr. before death and from control animals have been incubated in vitro. Output of Delta(4)-3-oxo steroids (0.2mumole/g. wet wt./hr. in control tissue) was linear for 4hr., and was increased by approx. 70% in slices from luteinizing hormone-treated rats. Rate of oxygen consumption (90.0+/-4.6mumoles/g. wet wt./hr.) was linear for 3hr. and unaltered by luteinizing hormone treatment or addition of glucose (1mg./ml.) to the medium. 2. In slices from control animals, steady-state rate of glucose uptake was 78.0+/-2.9mug. atoms of carbon/g. wet wt./hr.; steady-state rates of lactate output, pyruvate output and incorporation of [U-(14)C]-glucose carbon atoms into carbon dioxide and total lipid extract were 60.7+/-0.9, 2.4+/-0.1, 18.0+/-1.1 and 0.7+/-0.1mug. atom of carbon/g. wet wt./hr. and accounted for 104.5+/-1.9% of the glucose uptake. In slices from luteinizing hormone-treated rats, glucose uptake and outputs of lactate, pyruvate and [(14)C]carbon dioxide were increased by approx. 25%, and 108.4+/-3.2% of the glucose uptake could be accounted for. 3. The total lipid extract was separated by thin-layer chromatography and saponification. Of the (14)C incorporated into this fraction during incubation with [U-(14)C]glucose 97% was found in the fractions containing glyceride glycerol and less than 3% in the fractions containing sterols, steroids or fatty acids. Appreciable quantities of (14)C were incorporated into these lipid fractions from [1-(14)C]acetate. 4. From a consideration of the tissue glycogen content, the specific activities of [(14)C]lactate and glucose 6-phosphate (C-1) derived from [1-(14)C]-, [6-(14)C]- and [U-(14)C]-glucose, and the ratio of [(14)C]carbon dioxide yields from [1-(14)C]glucose and [6-(14)C]glucose, it was concluded that there was no appreciable glycogenolysis or flow through the pentose phosphate cycle. 5. In ovary slices from both control and luteinizing hormone-treated animals, glucose in vitro raised the incorporation rate of (14)C from [1-(14)C]acetate into sterols and steroids. Luteinizing hormone in vivo stimulated the incorporation rate in vitro but only in the presence of glucose. 6. In slices incubated in medium containing [(3)H]water, [(14)C]sorbitol and glucose (1mg./ml.), the total water space (865+/-7.1mul./g.) and the extracellular water space (581+/-22mul./g.) were unchanged by luteinizing hormone treatment in vivo but the glucose space was raised from 540+/-23.6mul./g. to 639+/-31.3mul./g. 7. Luteinizing hormone treatment was found to lower the tissue concentration of the hexose monophosphates and to increase the total activity of hexokinase, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and possibly of phosphofructokinase. 8. The kinetic properties of a partially purified preparation of phosphofructokinase were found to be qualitatively similar to those from other mammalian tissues. 9. The results are discussed with reference to both the role of glucose metabolism in steroidogenesis and the mechanism by which luteinizing hormone increases the rate of glucose uptake.

Acetates↗

Control of the tricarboxylate cycle and its interactions with glycolysis during acetate utilization in rat heart.

1. Transient and steady-state changes caused by acetate utilization were studied in perfused rat heart. The transient period occupied 6min and steady-state changes were followed in a further 6min of perfusion. 2. In control perfusions glucose oxidation accounted for 75% of oxygen utilization; the remaining 25% was assumed to represent oxidation of glyceride fatty acids. With acetate in the steady state, acetate oxidation accounted for 80% of oxygen utilization, which increased by 20%; glucose oxidation was almost totally suppressed. The rate of tricarboxylate-cycle turnover increased by 67% with acetate perfusion. The net yield of ATP in the steady state was not altered by acetate. 3. Acetate oxidation increased muscle concentrations of acetyl-CoA, citrate, isocitrate, 2-oxoglutarate, glutamate, alanine, AMP and glucose 6-phosphate, and lowered those of CoA and aspartate; the concentrations of pyruvate, ATP and ADP showed no detectable change. The times for maximum changes were 1min, acetyl-CoA, CoA, alanine and AMP; 6min, citrate, isocitrate, glutamate and aspartate; 2-4min, 2-oxoglutarate. Malate concentration fell in the first minute and rose to a value somewhat greater than in the control by 6min. There was a transient and rapid rise in glucose 6-phosphate concentration in the first minute superimposed on the slower rise over 6min. 4. Acetate perfusion decreased the output of lactate, the muscle concentration of lactate and the [lactate]/[pyruvate] ratio in perfusion medium and muscle in the first minute; these returned to control values by 6min. 5. During the first minute acetate decreased oxygen consumption and lowered the net yield of ATP by 30% without any significant change in muscle ATP or ADP concentrations. 6. The specific radioactivities of cycle metabolites were measured during and after a 1min pulse of [1-(14)C]acetate delivered in the first and twelfth minutes of acetate perfusion. A model based on the known flow rates and concentrations of cycle metabolites was analysed by computer simulation. The model, which assumed single pools of cycle metabolites, fitted the data well with the inclusion of an isotope-exchange reaction between isocitrate and 2-oxoglutarate+bicarbonate. The exchange was verified by perfusions with [(14)C]bicarbonate. There was no evidence for isotope exchange between citrate and acetyl-CoA or between 2-oxoglutarate and malate. There was rapid isotope equilibration between 2-oxoglutarate and glutamate, but relatively poor isotope equilibration between malate and aspartate. 7. It is concluded that the citrate synthase reaction is displaced from equilibrium in rat heart, that isocitrate dehydrogenase and aconitate hydratase may approximate to equilibrium, that alanine aminotransferase is close to equilibrium, but that aspartate transamination is slow for reasons that have yet to be investigated. 8. The slow rise in citrate concentration as compared with the rapid rise in that of acetyl-CoA is attributed to the slow generation of oxaloacetate by aspartate aminotransferase. 9. It is proposed that the tricarboxylate cycle may operate as two spans: acetyl-CoA-->2-oxoglutarate, controlled by citrate synthase, and 2-oxoglutarate-->oxaloacetate, controlled by 2-oxoglutarate dehydrogenase; a scheme for cycle control during acetate oxidation is outlined. The initiating factors are considered to be changes in acetyl-CoA, CoA and AMP concentrations brought about by acetyl-CoA synthetase. 10. Evidence is presented for a transient inhibition of phosphofructokinase during the first minute of acetate perfusion that was not due to a rise in whole-tissue citrate concentration. The probable importance of metabolite compartmentation is stressed.

Acetates↗

The enzymic deacylation of phospholipids and galactolipids in plants. Purification and properties of a lipolytic acyl-hydrolase from potato tubers.

An enzyme preparation that catalyses the deacylation of mono- and di-acyl phospholipids, galactosyl diglycerides, mono- and di-glycerides has been partially purified from potato tubers. The preparation also hydrolyses methyl and p-nitrophenyl esters and acts preferentially on esters of long-chain fatty acids. Triglycerides, wax esters and sterol esters are not hydrolysed. The same enzyme preparation catalyses acyl transfer reactions in the presence of alcohols and also catalyses the synthesis of wax esters from long-chain alcohols and free fatty acids. Gel filtration, DEAE-cellulose chromatography and free-flow electrophoresis failed to achieve any separation of the acyl-hydrolase activities towards different classes of acyl lipids (phosphatidylcholine, monogalactosyl diglyceride, mono-olein, methyl palmitate and p-nitrophenyl palmitate) or any separation of these activities from a major protein component. For each class of lipid the acyl-hydrolase activity was subject to substrate inhibition, was inhibited by relatively high concentrations of di-isopropyl phosphorofluoridate and the pH responses were changed by Triton X-100. The hydrolysis of phosphatidylcholine was stimulated 30-40-fold by Triton X-100. The specific activities of the potato enzyme with galactolipids were at least 70 times higher than those reported for a homogeneous galactolipase enzyme purified from runner bean leaves. The possibility that a single lipolytic acyl-hydrolase enzyme is responsible for the deacylation of several classes of acyl lipid is discussed.

Carbon Isotopes↗

Mechanism of activation of pyruvate dehydrogenase by dichloroacetate and other halogenated carboxylic acids.

1. Monochloroacetate, dichloroacetate, trichloroacetate, difluoroacetate, 2-chloropropionate, 2,2'-dichloropropionate and 3-chloropropionate were inhibitors of pig heart pyruvate dehydrogenase kinase. Dichloroacetate was also shown to inhibit rat heart pyruvate dehydrogenase kinase. The inhibition was mainly non-competitive with respect to ATP. The concentration required for 50% inhibition was approx. 100mum for the three chloroacetates, difluoroacetate and 2-chloropropionate and 2,2'-dichloropropionate. Dichloroacetamide was not inhibitory. 2. Dichloroacetate had no significant effect on the activity of pyruvate dehydrogenase phosphate phosphatase when this was maximally activated by Ca(2+) and Mg(2+). 3. Dichloroacetate did not increase the catalytic activity of purified pig heart pyruvate dehydrogenase. 4. Dichloroacetate, difluoroacetate, 2-chloropropionate and 2,2'-dichloropropionate increased the proportion of the active (dephosphorylated) form of pyruvate dehydrogenase in rat heart mitochondria with 2-oxoglutarate and malate as respiratory substrates. Similar effects of dichloroacetate were shown with kidney and fat-cell mitochondria. Glyoxylate, monochloroacetate and dichloroacetamide were inactive. 5. Dichloroacetate increased the proportion of active pyruvate dehydrogenase in the perfused rat heart, isolated rat diaphragm and rat epididymal fat-pads. Difluoroacetate and dichloroacetamide were also active in the perfused heart, but glyoxylate, monochloroacetate and trichloroacetate were inactive. 6. Injection of dichloroacetate into rats starved overnight led within 60 min to activation of pyruvate dehydrogenase in extracts from heart, psoas muscle, adipose tissue, kidney and liver. The blood concentration of lactate fell within 15 min to reach a minimum after 60 min. The blood concentration of glucose fell after 90 min and reached a minimum after 120 min. There was no significant change in plasma glycerol concentration. 7. In epididymal fatpads dichloroacetate inhibited incorporation of (14)C from [U-(14)C]glucose, [U-(14)C]fructose and from [U-(14)C]lactate into CO(2) and glyceride fatty acid. 8. It is concluded that the inhibition of pyruvate dehydrogenase kinase by dichloroacetate may account for the activation of pyruvate dehydrogenase and pyruvate oxidation which it induces in isolated rat heart and diaphragm muscles, subject to certain assumptions as to the distribution of dichloroacetate across the plasma membrane and the mitochondrial membrane. 9. It is suggested that activation of pyruvate dehydrogenase by dichloroacetate could contribute to its hypoglycaemic effect by interruption of the Cori and alanine cycles. 10. It is suggested that the inhibitory effect of dichloroacetate on fatty acid synthesis in adipose tissue may involve an additional effect or effects of the compound.

Acetamides↗

Lipids associated with bovine kidney glomerular basement membranes.

1. After incubation of bovine glomeruli with D-[U-14C]glucose, about 21% of the total radioactivity is found in lipid extracts of glomerular basement membranes. 2. The concentration of lipids in glomerular basement membranes (4.3% of dry wt.) is lower than in the residual glomerular particles (10.8% of dry wt.). The concentrations of neutral lipids (13.9%), phospholipids (46.7%) and cholesterol (37.9%) in the total lipid extract of the glomerular basement membranes, however, differ from those in the residual glomerular particles (15.6, 54.0 and 30.9% respectively). Though residual glomerular particles show a higher lipid content, the radioactivity in this fraction only amounts to 38% of that found in the glomerular basement membranes. 3. The specific radioactivity of total glomerular basement-membrane lipids (12 600 d.p.m./mg) is about 4 times as high as that of the glomerular basement membranes. The specific radioactivities of the individual lipid components, however, differ. The highest values are found for phosphatidylcholine and triacylglycerols. The largest proportion of the radioactivity is found in the glycerol of the glycerides. The radioactivity in the fatty acids is much less and does not differ significantly in the various classes of lipids. 4. G.1.c. of methyl esters of the fatty acids does not reveal a clear difference between the fatty acid compositions of glomerular basement membranes and residual glomerular particles. 5. Treatment of glomerular basement-membrane preparations with ultrasound, the generally used procedure for glomerular basement-membrane preparations, drastically decreases the lipid content of glomerular basement membranes. 6. It is concluded that lipids are associated with the basement membranes. Further, the comparatively high radioactive labelling suggests that glomerular basement-membrane lipids may be an interesting class of substances for further pathological studies.

Animals↗

Fatty acid synthesis in the perfused liver of adrenalectomized rats.

1. Fatty acid synthesis, measured in the perfused liver of fed adrenalectomized rats with 3H2O and 14C-labelled precursors, was less than in control sham-operated rats. 2. This defect was more extensive for synthesis of fatty acids incorporated into triacylglycerols than into phospholipids. 3. There was impairment in desaturation and export of newly synthesized fatty acid. 4. Fatty acid synthesis and desaturation were restored to normal rates 5h after treatment with cortisol in vivo. 5. Fatty acid synthesis was seasonally variable, being highest in the winter; the impairment after adrenalectomy was observed in all seasons. 6. In perfusions with oleate (0.7 mM), no further impairment in fatty acid synthesis was discerned in livers from adrenalectomized rats, in which the rate resembled that in control livers. 7. No defect in the incorporation of oleate into glycerides was discerned in livers from adrenalectomized rats. 8. Cortisol exerted no stimulatory effect on fatty acid synthesis when added to perfusion media. 9. The impairment in hepatic lipogenesis, demonstrable after adrenalectomy, shows that adrenal glucocorticoids promote hepatic capacity for fatty acid synthesis de novo, at least in intact non-diabetic rats. It is suggested that this effect is mediated by insulin, perhaps through direct action on the liver.

Adrenal Glands↗

Changes in pulmonary surfactant and phosphatidylcholine metabolism in rats exposed to chrysotile asbestos dust.

1. Pulmonary surfactant was isolated from rats that had been exposed to chrysotile asbestos dust for from 3 days to 15 weeks. 2. Asbestos-treated rats showed a progressive increase in amounts of surfactant. After 15 weeks, treated animals contained 4 times as much as non-treated. 3. No significant change was seen in the total protein or total fatty acid composition of surfactant with exposure. 4. The increase in surfactant phosphatidylcholine normally seen on maturation of rat lung was accelerated by exposure of animals to asbestos. 5. An increase in the activity of phosphorylcholine glyceride transferase in lung homogenates and free cell populations was found. 6. Lysosomal phospholipase A was relatively unaffected by dust exposure. 7. It is suggested that the increase in surfactant amounts could be due to an increase in its synthesis without a corresponding alteration in its degradation.

Animals↗