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PubMed1986

Fetal lung surfactant lipid synthesis from glycogen during organ culture.

The role of fetal lung glycogen as a precursor for lipids during late gestational development was explored by a combination of in vivo labeling with [U-14C]glucose, administered directly to rat fetuses at 18.5 days, and in vitro assessment using an organ explant culture system. Our major objectives were to demonstrate that radioactivity was transferred specifically and preferentially to surfactant lipids, as glycogenolysis occurred, and to determine the molecular distribution of 14C labeling in newly synthesized phosphatidylcholine (PC). Surfactant and residual (non-surfactant) lipids were separated by sucrose density gradient centrifugation, and other subcellular fractions such as microsomes were isolated by subsequent centrifugations. After 72 h of culture, there was a 5.7-fold increase in the concentration of PC in the surfactant fraction, which contributed 8.8% of total PC at the beginning and 29.6% (P less than 0.001) at the end of the 72 h period. The labeling of PC in the surfactant fraction increased markedly during culture, but there was no significant change in the residual fraction or microsomal PC. Hydrolysis of surfactant PC indicated that the radioactivity was predominantly located in the fatty acyl portion of the molecule, both before and after culture; however, PC glycerol labeling also increased significantly during culture. The distribution of PC radioactivity was similar in the residual fraction and microsomes, with the majority of 14C in the fatty acids. Neutral lipid radioactivity also increased significantly in both the surfactant (240%) and residual (136%) fractions. Quantitation of the changes in radioactivity among subcellular components during lung explant culture indicated that the greatest decrease occurred in glycogen, whereas only lipids, particularly those of the surfactant fraction, were found to show significant increases. These results support the hypothesis that glycogen, which accumulates in fetal lung prior to augmented surfactant production, can supply precursors for synthesis of functionally essential pulmonary phospholipids.

Animals↗

PubMed1984

Efflux of gamma-aminobutyric acid from and appearance of free arachidonic acid inside synaptosomes.

When synaptosomes were depolarized in the presence of Ca2+, or when Ca2+ was added to synaptosomes pretreated with Ca2+ ionophore (A23187), free arachidonic acid was clearly increased within synaptosomes, and at the same time an efflux of gamma-aminobutyric acid from synaptosomes was observed. Moreover, when synaptosomes labelled with [14C]arachidonic acid were depolarized in the presence of Ca2+, there was a significant decrease in the radioactivity of the fatty acid of phosphatidylinositol and phosphatidylcholine. Exogenously added arachidonic acid, but not other fatty acids, stimulated the efflux of gamma-aminobutyric acid in the absence of Ca2+. These observations suggest that the release of arachidonic acid from phospholipids is an intrinsic part of the biochemical mechanism that modulates the gamma-aminobutyric acid efflux.

Animals↗

PubMed1990

Concentrations of long-chain acyl-acyl carrier proteins during fatty acid synthesis by chloroplasts isolated from pea (Pisum sativum), safflower (Carthamus tinctoris), and amaranthus (Amaranthus lividus) leaves.

Fatty acid synthesis from [1-14C]acetate by chloroplasts isolated from peas and amaranthus was linear for at least 15 min, whereas incorporation of the tracer into long-chain acyl-acyl carrier protein (ACP) did not increase after 2-3 min. When reactions were transferred to the dark after 3-5 min, long-chain acyl-ACPs lost about 90% of their radioactivity and total fatty acids retained all of theirs. Half-lives of the long-chain acyl-ACPs were estimated to be 10-15 s. Concentrations of palmitoyl-, stearoyl-, and oleoyl-ACP as indicated by equilibrium labeling during steady-state fatty acid synthesis, ranged from 0.6-1.1, 0.2-0.7, and 0.4-1.6 microM, respectively, for peas and from 1.6-1.9, 1.3-2.6, and 0.6-1.4 microM, respectively, for amaranthus. These values are based on a chloroplast volume of 47 microliters/mg chlorophyll and varied according to the mode of the incubation. A slow increase in activity of the fatty acid synthetase in safflower chloroplasts resulted in long-chain acyl-ACPs continuing to incorporate labeled acetate for 10 min. Upon re-illumination following a dark break, however, both fatty acid synthetase activity and acyl-ACP concentrations increased very rapidly. Palmitoyl-ACP was present at concentrations up to 2.5 microM in safflower chloroplasts, whereas those of stearoyl- and oleoyl-ACPs were in the lower ranges measured for peas. Acyl-ACPs were routinely separated from extracts of chloroplasts that had been synthesising long-chain fatty acids from labeled acetate by a minor modification of the method of Mancha et al. (Anal. Biochem., 1975, 68, 600-608). The results compared favorably with those obtained using alternative analytical methods such as adsorption to filter paper and partition chromatography on silicic acid columns. The acyl-ACP which coprecipitated with ammonium sulfate was not affected by treatments with neutral hydroxylamine or borohydride, whereas that eluted from silicic acid was relatively easily derivatized. A single radioactive polypeptide of Mr 11,500 from pea and amaranthus chloroplasts was revealed by autoradiography of gels from sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the silicic acid eluates.

Acetates↗

PubMed1975

Biosynthesis of fatty acids from acetate in soybean suspension cultures.

Suspension cultures of finely divided soybean cells established from callus were incubated with sodium [1(14)C] acetate for periods up to 86 hr. Lipids and fatty acids were analyzed for radioactivity in samples harvested at logarithmic time periods. Incorporation of acetate into cell lipid was directly proportional to the logarithm of time up to 32 hr, after an initial lag of 4-6 hr. Most of the lipid radioactivity was found in the phospholipid fraction, and all common soybean fatty acids became labeled within 6 hr. The order of labeling and distribution of radioactivity with time were essentially the same as in tissues from intact growing plants. These results support the concept of sequential desaturation of oleic acid in the cells. It was concluded that valid studies of the biosynthesis of common lipids in the soybean can be carried out for extended periods of time by use of undifferentiated cells in suspension cultures.

Acetates↗

PubMed1979

In vitro lipid metabolism in the rat pancreas. II. Effects of secretagogues on fatty acid metabolism, net lipolysis and ATP levels.

1. The concentration of carbamylcholine, bombesin, pancreozymin, pentagastrin and secretin evoking a similar 4--5-fold maximal increase in amylase secretion from rat pancreatic fragments were 3.10(-6), 10(-7), 10(-8), 3.10(-6), and 3.10(-6) M, respectively. The maximal concentration of vasoactive intestinal peptide tested (3.10(-6) M) increased amylase secretion by 250%. The six secretagogues could be separated into two groups according to their effects on lipid metabolism and ATP levels. 2. When used at their optimal concentrations, carbamylcholine, bombesin, pancreozymin, and pentagastrin lowered pancreatic ATP levels by 18-26% and increased net release of free fatty acids by 68-105%. 3. The effects of 3.10(-6) M carbamylcholine and 10(-8) M pancreozymin on the metabolism of 3H2O, D-[U-14C]glucose and [1-14C]acetate were similar; the incorporation of radioactivity in the fatty acid moiety of glycerolipids decreased by 20--50% whereas the incorporation of 3H from 3H2O and of 14C from [U-14C]glucose increased by 20--35% in the glycerol moiety. In addition, the oxidation of [U-14C]glucose, [1-14C]acetate and [1-14C]palmitate to 14CO2 increased by 15--32% while the esterification of [1-14C]palmitate, [1-14C]-linoleate, and [1-14C]arachidonate was inhibited by 14--23%. The spectrum of fatty acids labeled with [1-14C]acetate indicated an inhibition of the malonic acid pathway whereas the elongation of polyenoic fatty acids was unaltered.

Acetyl Coenzyme A↗

PubMed1987

Capacity of the European eel (Anguilla anguilla) to elongate and desaturate dietary linoleic acid.

The ability of eels (Anguilla anguilla) to further desaturate and chain elongate linoleic acid, 18:2n-6, was studied by feeding diets containing either corn oil or a fish oil to groups of elvers for 12 wk and analyzing proportions of fatty acids in tissue lipids. Over the 12-wk period elvers given both dietary treatments increased in weight by fourfold. The proportion of arachidonic acid, 20:4n-6, present in polar lipids of elvers fed the diet containing corn oil increased from an initial value of 5% by weight to 12% by weight; the corresponding value for elvers given a diet containing fish oil, with little linoleic acid in it, was less than 4% by weight. The capacity of this fish to modify dietary linoleic acid metabolically was confirmed by examining the metabolic fate of radioactive carbon after giving [1-14C]linoleic acid orally to eels. Seven days after administration of the linoleic acid approximately 10% of the radioactivity recovered in liver fatty acids was present in trienes and tetraenes with about 4% occurring in arachidonic acid. Compositional analyses from the feeding experiment also indicated that dietary docosaenoic acid, 22:1n-11, is preferentially oxidized by eels.

Anguilla↗

PubMed1984

On the formation of alpha-hydroxy fatty acids. Evidence for a direct hydroxylation of nonhydroxy fatty acid-containing sphingolipids.

When Tetrahymena pyriformis, strain NT-1, was warmed from a growth temperature of 15 degrees C to 39 degrees C, there was a rapid conversion of its sphingolipids from the nonhydroxy fatty acid-containing ceramide aminoethylphosphonate (NCAEP) predominant at low temperature to the alpha-hydroxy fatty acid-containing analog (HCAEP). The fatty acid composition of the freshly formed HCAEP strongly resembled that of the original NCAEP pool. An extensive utilization of NCAEP long chain bases for HCAEP formation was shown by prelabeling the NCAEP bases with [14C]serine. The specific radioactivities of both fatty acids and long chain bases of the two sphingolipid classes of cells prelabeled with [3H]palmitic acid at 15 degrees C and then warmed to 39 degrees C were compatible with a direct hydroxylation of the intact ceramide aminoethylphosphonate or free ceramide formed from it. Exogenously added alpha-hydroxypalmitic acid was not incorporated into the sphingolipids intact, but there was an active alpha-oxidation of alpha-hydroxy fatty acids, yielding nonhydroxy fatty acids one carbon atom shorter in length. In vitro experiments failed to demonstrate a direct hydroxylation of NCAEP, and nonhydroxy fatty acid-containing free ceramides were hydroxylated only sparingly. This inefficient hydroxylation is attributed to the rapid enzymatic hydrolysis of these substrates in vitro and to a limited availability of the added ceramides to the hydroxylating enzymes. The weight of the evidence from this study strongly favors the alpha-hydroxylation of fatty acids only when they are bound as elements of sphingolipids.

Animals↗

PubMedDate not supplied

[The utilization of [9,10-(3)H] stearic and [1-(14)C] linolenic acids in the in-vitro synthesis of lipids in ruminant tissues].

The radioactivity of the synthesized total lipids after in vitro incubation of liver, skeletal muscle and adipose tissue homogenates from ruminants with [9,10-3H]stearic acid was 3.5, 2.9 and 6.6 times higher than after the incubation of these organs and tissues with [1-14C]linolenic acid, respectively compared with the radioactivity of non-esterificant fatty acids fraction being in this case 2.0, 1.7 and 1.6 times lower, respectively. The radioactivity of phospholipids, di- and triglycerides, free and esters cholesterols after the incubation of liver, skeletal muscle and adipose tissue homogenates with [9,10-3H]stearic acid comprised 30.6-33.5, 13.2-18.0, 23.2-32.5, 18.2-23.0, 2.8-3.3 per cent of total lipid radioactivity, respectively, and after the incubation with [1-14C]linolenic acid this correlation was as follows: 46.5-51.5,17.8-33.3, 4.0-10.6, 9.2-15.4 and 0.6-4.5 per cent of total lipids radioactivity.

Adipose Tissue↗

PubMed1989

Lipogenesis and cholesterogenesis de novo in liver and adipose tissue. Alterations of lipid metabolism by the effect of short- and long-term thioacetamide administration to rats.

Enzyme activities related to fatty acid synthesis were determined in liver extracts of rats treated with thioacetamide (TAM) for 8 weeks. Lipogenesis and cholesterogenesis in vivo were evaluated both in liver and in epididymal adipose tissue. The enzymatic activities of ATP-citrate lyase, acetyl CoA carboxylase, fatty acid synthetase, glycerol kinase and NAD-kinase decrease progressively when TAM was chronically administered. However, in the same experimental conditions malic enzyme and other NADP-enzymes were noticeably increased. This increase can be related to an excess of NADPH production necessary for detoxification rather than for lipogenesis. The rate of in vivo incorporation of 3H2O into non-saponifiable fraction in liver showed an increase in the acute phase (1-3 days) of TAM-treatment. In the chronic phase of TAM intoxication this rate returned to values close to normality. The rate of in vivo incorporation of 3H2O to fatty acid fraction increased in the liver during the acute phase of TAM-treatment and showed a sharp decrease during the subacute and chronic phases of the intoxication. At the end of the 60-day period of TAM-treatment, the radioactivity incorporated into fatty acids was significantly lowered. These data showed that the alterations in hepatic lipogenesis observed during TAM administration are related to changes in the activities of lipogenic enzymes and probably are a consequence of alterations in plasma insulin concentration. Disturbances in lipid metabolism should play an important role in the pathogenesis of liver damage and its physiological significance could involve metabolic changes in proliferative and neoplastic liver diseases.

Acetamides↗

PubMed1994

Temperature-dependent phospholipid degradation in the rat liver during preservation for transplantation. A comparison between different preservation solutions.

For the development of liver injury during preservation for transplantation, phospholipid degradation may be of importance. We therefore measured the degradation of [3H]-arachidonic acid (20:4)- and [14C]-linoleic acid (18:2)-labeled phospholipids during cold and warm preservation of rat livers in Eurocollins, University of Wisconsin, or a recently developed dextran-based solution. The amount of labeled phospholipids decreased with time during preservation at 37 degrees C with a concomitant increase in that of labeled fatty acids. The rate of degradation of [3H]-20:4-labeled phospholipids did not differ from that of [14C]-18:2-labeled phospholipids. The reduction of phosphatidylcholine and phosphatidylethanolamine radioactivity accounted for the major reduction of phospholipid radioactivity while there was no decrease in phosphatidylinositol radioactivity. In contrast, no phospholipid hydrolysis occurred during preservation at 4 degrees C or at 21 degrees C. The results were not different whether the livers were preserved in EC, UW, or the dextran-based preservation solution. During reperfusion of livers either immediately after removal or after cold storage at 4 degrees C in EC or UW solutions for 24 hr, a moderate increase in the [3H] and [14C] radioactivity of free fatty acids and triacylglycerol and in that of [3H] in PE occurred. There was, however, no difference between the three groups. Thus, during liver preservation at 37 degrees C, phospholipid degradation occurs, and its rate is independent of the preservation medium. In contrast, at the temperature used when preserving livers for transplantation, there is no phospholipid degradation. The cold storage in either EC or UW solution does not influence the net hydrolysis and the transesterification reaction that the phospholipids undergo during warm reperfusion of the isolated livers.

Adenosine↗

PubMed1982

Trans fatty acids: transport and positional specificity in rat placental lecithin.

Differences in positional incorporation of trans and cis isomers of octadecenoic and octadecadienoic acids in placental lecithin of rats was demonstrated. A 14C-labeled albumin complex of elaidic, oleic, linoelaidic, or linoleic acid was injected into the jugular vein of pregnant rats. 6 h later 45-64% of the total radioactivity in placental lipids was found in phospholipids (PL), with a major portion of the label incorporated into choline phosphoglycerides (CPC). Following hydrolysis of placental CPC by phospholipase A2, distribution of radioactivity within isolated fatty acids and lysolecithin suggested preferential incorporation of t,t-18:2 at position 2 and a nearly equal distribution of t-18:1 at positions 1 and 2.

Animals↗

PubMedDate not supplied

Do we still need to collect stool? Evaluation of visualized fatty acid absorption: experimental studies using rats.

BACKGROUND: Short-gut syndrome is likely to impair enteric fat utilization. This study was undertaken to develop a clinical test of lipid absorption without fecal collection. METHODS: The absorption of enterally fed radioactive long-chain fatty acid, beta-methyl-p-(123I)-iodophenylpentadecanoic acid was investigated with continuous chyle collection in rats. The changes in excretion and time-dependent biodistribution of radioactivity of the enterally fed agent were assessed in normal control animals. Similarly, sequential urinary excretion and biodistribution were studied along with scintigraphy using sham-operated and short-gut animals. RESULTS: Approximately 64% of the enterally fed radioactivity was recovered in the collected chyle (24 hours). A comparison of normal control, sham-operated, and short-gut animals showed significantly less urinary and greater fecal excretions of radioactivity in short-gut animals. With the use of sequential scintigraphy, the small intestine, whole-body soft tissues, and urinary bladder were well visualized in sham-operated animals, whereas the large intestine and feces were demonstrated earlier in short-gut animals. CONCLUSIONS: Our results suggest that enteral feeding of the agent might be feasible for determining lipid absorption from the the dynamic changes of radioactivity in visualized abdominal organs and in urine.

Animals↗

PubMed1978

[Pathways of intracellular cholesterol metabolism in a model study].

We had concluded from former own investigations that the cells in the arteriosclerotic plaque effect a change of the ester proportion of cholesterol. One of the possible mechanisms ible bond and from double unsaturated (linoleic acid) to higher unsaturated acids. Therefore we investigated by radioactive labelling of the fatty acid moity of cholesterol esters whether such desaturation reactions take place in the model experiment. For this purpose we implanted cholesterol stearate which was 14C-labelled in the proportion of fatty acid subcutaneously into the skin of a rat. We demonstrated radiohistochromatographically that after 7 to 14 days the fraction of the cholesterol esters with 1 double bond was additionally labelled. Other fractions were not labelled. From this results that the proportion of the saturated fatty acid of the cholesterol ester is actually desaturated, in which case the desaturation as we expect only goes to the fraction with one double bond, because the double unsaturated linoleic acid is not synthetized in vivo in the mamal.

Animals↗

PubMed1975

Biochemistry of development in insects. Incorporation of fatty acids into different lipid classes.

1. To study the different metabolic behaviour of various stages of development of the insect Ceratitis capitata, the incorporation of labelled decanoic, lauric, myristic, palmitic, stearic, oleic, and linoleic acids into triacylglycerols by insect homogenates was investigated. The time-course of incorporation of labelled fatty acids was firstly studied by using oleic acid; it showed that after 10 min of incubation the levels of radioactivity incorporated into triacylglycerols and those remaining in the free fatty acids were practically unchanged. 2. All labelled fatty acids were efficiently incorporated by larval homogenates; however, most of the radioactivity remained as free fatty acids in the presence of pharate adult homogenates, palmitic, and stearic acids being the most scarcely incorporated by this stage of development of the insect. 3. Plots of triacylglycerol and free fatty acid radioactivites versus the stage of development defined a crossing-zone in coincidence with the larval-pupal apolysis. This metabolic difference between larval and pharate adult homogenates could not be explained through differences in the acyl-CoA synthetase activity of the insect; this enzyme activity was notably higher in pharate adult homogenates than in the larval homogenates whatever would be the nature of the fatty acid. 4. [14C]Triolein was scarcely hydrolyzed by both larval and pharate adult homogenates. 5. Double-label experiments were carried out by incorporating either [3H]oleic acid or [3H]-palmitic acid and [14C]glycerol 3-phosphate by larval and pharate adult homogenates at different incubation intervals. Diacylglycerols, triacylglycerols, and phosphoglycerides were isolated and the 14C/3H molar ratio calculated. Results suggest the existence of a different acyltransferase activity in the different stages of development of the insect.

Animals↗

PubMed1987

The incorporation of fatty acids into triacylglycerols of isolated neuronal nuclear envelopes: the influence of thiol reducing reagents and chromatin.

Using [3H]arachidonate, ATP, coenzyme A, MgCl2, EGTA and CMP, triacylglycerols were labelled in an isolated neuronal nuclear fraction, N1 (from immature rabbit cerebral cortex). When the radioactive nuclear fraction N1 was subfractionated, 75% of the labelled triacylglycerol product was located in the nuclear envelope fraction, E, indicating that the fatty acid incorporation was taking place at the nuclear membrane. However, when nuclear envelope fraction E was first isolated and then incubated with radioactive fatty acid, a significant incorporation into triacylglycerol was found only when nuclear envelope fractions had been prepared in the presence of dithiothreitol or mercaptoethanol. The use of the thiol compounds during the isolation of nuclear envelope fraction E led to specific incorporation rates (based on phospholipid content) which were at best 45-56% of the corresponding values seen for the parent nuclear N1 fraction. This was seen for nuclear envelope fractions isolated by two different procedures. Specific rates for acyl-CoA synthetase and diacylglycerol generation (by cholinephosphotransferase) were measured in nuclear envelope fractions and found to be similar to specific rates for these enzymes in the nuclear N1 fraction. The deficiency in triacylglycerol labelling in nuclear envelope fractions was likely due to impaired diacylglycerol acyltransferase activity. Higher specific rates of triacylglycerol labelling (82-90% of N1 values) were seen in nuclear envelope fractions assayed very shortly after preparation and in another subfraction of nuclear fraction N1 which contained small amounts of phospholipid and high concentrations of nucleates and protein. These data suggest that triacylglycerol formation may be maintained by the presence of chromatin, while in its absence there is a loss of acylation activity in nuclear envelope fractions.

Animals↗

PubMed1992

Synthesis of beta-hydroxy fatty acids and beta-amino fatty acids by the strains of Bacillus subtilis producing iturinic antibiotics.

The iturinic antibiotics, which contain long chain beta-amino acids, are produced by Bacillus subtilis. Screening these strains for the presence of a possible precursor of the iturinic antibiotics, we isolated a lipopeptide containing beta-hydroxy fatty acids. The structure of this compound was studied and it appears to be identical or structurally very similar to surfactin. The carbon chain of its beta-hydroxy fatty acids was n C16, iso C16, iso C15 or anteiso C15. The percentages of each beta-hydroxy fatty acids varied according to the strain producing iturinic antibiotics and were influenced by addition of branched-chain alpha-amino acids to the culture medium. These results demonstrate for the first time that iso C14 beta-hydroxy fatty acid is a constituent present in such a surfactin like lipopeptide. Besides, the presence of radioactive beta-hydroxy fatty acids in the phospholipids when the strains were grown in the presence of sodium [14C]acetate seems also characterize the different strains producing iturinic antibiotics.

Amino Acid Sequence↗

PubMed1975

The effect of essential fatty acid deficiency upon fatty acid uptake by the brain.

Young adult rats, either control or essential fatty acid deficient, were administered either [3-H] oleic acid or [3-H] arachidonic acid by stomach tube. In addition, a group of control rats was given [3-H] palmitic acid. The rats were killed at various times therafter, and the radioactivity of the lipids of brain and plasma was examined. In confirmation of previous work, the blood lipid label was found to rise rapidly and then fall, wheras the activity of brain lipids increased slowly and did not show a decline through the 24-h period studied. Analysis of the brain uptake data according to first-order kinetics confirmed the impressions gained from visual inspection of the data. The initial rate of uptake of arachidonic acid was about 4.5 times that of oleic acid in control animals and in deficient animals. Essential fatty acid deficiency, however, did not induce an altered rate of uptake for either oleic acid or arachidonic acid. The rate of uptake of palmitic acid by control rats was not significantly different from that of oleic acid. Even though the initial rates of incorporation of oleic and arachidonic acids were not changed during essential fatty acid deficiency, the final levels of radioactivity obtained in brain lipids were higher in deficient rats with both fatty acids. The plateau value obtained with oleic acid was 1.5 times higher in deficient animals, while the plateau value for arachidonic acid was 1.7 times higher. An experiment in which deficient animals were allowed access to a control diet for 12 or 24 h prior to the labeling experiment suggested that the higher levels of radioactivity found in brain lipids of deficient animals was not due to an isotope dilution effect. Such animals still displayed the labeling pattern of deficient animals with arachidonic acid, while the results with oleic acid varied somewhat. Our results suggest that essential fatty acid deficiency does not alter the ability of the brain to take up the fatty acids studied. However, the fatty acids, especially arachidonic, are retained in the brain to a greater extent in the deficient animals.

Animals↗

PubMed1973

Effect of halofenate and clofibrate on growth and lipid synthesis in Saccharomyces cerevisiae.

Halofenate-free acid (HFA) inhibited the growth of Saccharomyces cerevisiae by 50% at a concentration of 0.34 mm. This inhibitory effect was prevented by addition of either oleate or acetate, but not by pyruvate. When cell growth was supported by oleate, HFA inhibited the incorporation of radioactive carbon from glucose-U-(14)C or pyruvate-2-(14)C into fatty acids and sterols. The incorporation of radioactive carbon into fatty acids and sterols from acetate-2-(14)C was unaffected by the compound. When cell growth was supported by either oleate or acetate, HFA inhibited the conversion of pyruvate-1-(14)C to (14)CO(2). These results suggest that HFA inhibits the conversion of pyruvate to acetate in yeast. Partially purified yeast pyruvate dehydrogenase was inhibited 50% by 5.5 mm HFA; however, the concentration required for 50% inhibition was considerably reduced when the enzyme was preincubated with the compound at room temperature. In a similar manner, the hypolipidemic agent clofibrate-free acid inhibited the growth of yeast by 50% at 3.0 mm. This inhibition was also prevented by acetate and not by pyruvate. In addition, clofibrate-free acid inhibited partially purified pyruvate dehydrogenase by 50% at a concentration of 37.0 mm.

Acetates↗