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Biomedical subjects

W E Lands

Publications and source records attributed to W E Lands.

At least 127 records · Page 7Linked to original sources
PubMed1975

Effectiveness of various unsaturated fatty acids in supporting growth and respiration in Saccharomyces cerevisiae.

The saturated fatty acid auxotroph of Saccharomyces cerevisiae, KD115, was used to determine the efficiency of various unsaturated fatty acids in supporting growth. The efficiency, as the number of cells produced per fmol of unsaturated fatty acid, ranged from zero for a number of acids to over 26 cells per fmol of eicosapentaenoic acid. Efficiencies tended to be higher for acids with fewer carbons or more double bonds. In a series of positional isomers of cis-octadecenoic acid, the delta9 isomer had the greatest efficiency (12 cells per fmol). Exogenous oleic acid was taken up and incorporated into cellular lipid early in the growth of the cells. Further growth proceeded with a decrease in the relative content of oleate in lipids until a minimum value of 9 mol % was reached at stationary phase. The initial concentration of supplemental acid did not affect the final mole % value. Other unsaturated fatty acids reached limiting values of mole % in phospholipid at stationary phase that were characteristic for the acid used. When cells were grown with glycerol as the carbon source, the efficiencies of most acids in supporting growth were one-third to one-fifth the value with glucose and the final mole % of supplement acid in phospholipid at stationary phase was two to five times greater. Apparently, mitochondrial energy transduction necessary for glycerol utilization requires higher levels of unsaturated fatty acids in membrane lipids than do extramitochondrial functions. The respiratory rate of mitochondria was not decreased at lower levels of oleic or palmitoleic acid in lipids, although respiratory control was lower when the mole % of unsaturated fatty acid was lower. Mitochondria from cells supplemented with eicosaenoic acid were found to have both low respiration and respiratory control. The decreased respiration of these mitochondria coincided with a decreased cytochrome content, not a decrease in respiration per mol of cytochrome.

Cell Division↗
PubMed1975

Requirements for unsaturated fatty acids for the induction on respiration in Saccharomyces cerevisiae.

Unsaturated fatty acids provided during the release from glucose repression were shown to be essential for derepression of respiration in an unsaturated fatty acid auxotroph of Saccharomyces cerevisiae (KD115). Cells derepressed in the presence of oleic acid contained three to six times as much cytochrome per cell as those derepressed in the absence of unsaturated fatty acid or those derepressed with eicosaenoic acid. The delta9 isomer was the most efficient of the cis-octadecenoic acid isomers in supporting that increase, and eicosaenoic acid supported an increase at only 15% the rate observed with oleic acid. Derepression, even in the presence of oleic acid, proceeded only after a lag of 3 hours. When glucose was removed prior to the addition of oleate, the lag was reduced by the time of the preincubation with glycerol. This result suggests that some processes necessary for increased respiration can proceed in the absence of an added unsaturated fatty acid, but these processes apparently require certain levels of unsaturated acids in the pre-existing lipids, since they occurred in cells whose membranes contained 50 mol % oleate, but not in cells containing only 20 mol %. These processes leading to eventual increased respiration were inhibited by cycloheximide but not chloramphenicol, suggesting that protein synthesis on cytoplasmic ribosomes but not mitochondrial ribosomes were required. Derepression in the absence of oleate for 3 hours lessened the inhibition or respiration induction by ethidium bromide. This result indicates that the transcription of mitochondrial DNA necessary for the induction of respiration may have occurred in the absence of added unsaturated fatty acid, but that some subsequent event required added esterified unsaturated fatty acid.

Chloramphenicol↗
PubMed1975

Inhibition of growth of microbial mutants by trans-octadecenoates.

A series of positional isomers of trans-octadecenoic acid were tested for their ability to support growth of microbial mutants that could not synthesize unsaturated fatty acids. The bacterial strain used (a variant of Escherichia coli 30E) grew with supplements of the trans isomers only at high temperatures (38 degrees) and with acids containing the trans-ethylenic bond between carbon atoms 8 through 13. The yeast mutant (Saccharomyces cerevisiae KD46) grew only with the 9-trans-octadecenoate giving cell yields about one-fifth those obtained with oleate. Although the trans isomers had little effect on the growth of the bacteria in the presence of oleate, they inhibited the growth of yeast with oleate. Inhibition was strongest for the 4, 6, 7, 11, and 12 isomers, almost negligible for the 8 isomer and of differing intermediate degrees for the others. The inhibitory effects had no correlation with the melting points of the acids and appeared to reflect selective action(s) on the metabolism of the cell. When the net yield of the yeast cultures with oleate was lowered by the effect of added trans acids, there was a marked accumulation of triglycerides and nonesterified acids in the cells. The marked increase in triglyceride content while phospholipid per cell remained relatively constant suggest that trans acids, in addition to forming inadequate membrane lipids, may also interfere with a basic control point in lipid metabolism.

Cell Division↗
PubMed1975

Structural requirements for time-dependent inhibition of prostaglandin biosynthesis by anti-inflammatory drugs.

Several anti-inflammatory drugs have been examined for their ability to cause a time-dependent destruction of the fatty acid oxygenase that produces prostaglandins. All of the time-dependent inhibitors contained carboxylic acid moieties, and in addition all but one of the drugs contained a halogen atom. Structural analogs (of the time-dependent inhibitors) lacking halogen atoms were unable to cause a time-dependent destruction of the enzyme. The time-dependent property of an inhibitor was totally eliminated after methylation of the carboxylate group. Methylation did not, however, alter the ability of the inhibitors to competitively inhibit the oxygenase. Thus, the reversible binding of the agents at the active site was not appreciably dependent upon the free carboxyl group, whereas the subsequent irreversible process was.

Anti-Inflammatory Agents↗
PubMed1975

Further studies of the kinetics of oxygenation of arachidonic acid by soybean lipoxygenase.

A kinetic model for soybean lipoxygenase (EC 1.13.11.12) has been examined by comparing results from extensive experimental data with theoretical data generated from a computer program. Kinetic constants have been established by closely fitting experimental and computer-generated data with both product formation versus time, and the more complex accelerative and decelerative relationships of velocity changes with time. It has been confirmed that activation of lipoxygenase by its hydroperoxide product is necessary for activity, and product removal gives inhibition in a manner quantitatively predicted by the model. The earliest accurate measurement of velocity (at 9 s) is a convenient index of the amount of product-activator present in reaction mixtures, and can be used to assay quantitatively the amount of product-activator. The results confirm that soybean lipoxygenase catalyzes a product-activated, substrate-inhibited oxygenation accompanied by a self-catalyzed destruction of its activity.

Animals↗
PubMed1975

Quantitative effects of unsaturated fatty acids in microbial mutants. IV. Lipid composition of Saccharomyces cerevisiae when growth is limited by unsaturated fatty acid supply.

The Saccharomyces cerevisiae mutant KD46 (ole 2), which is unable to synthesize unsaturated fatty acids, was grown on limiting amounts of different added unsaturated fatty acids. The acyl chain composition of the cellular lipid classes was determined in these cultures at different stages or growth. During growth on added oleic acid, there was no marked change in the mole percentage of phosphatidylcholine, phosphatidylethanolamine. phosphatidylinositol, or phosphatidylserine among the total phospholipids. Cells grown on palmitoleic, oleic, or linoleic acid showed a steady decrease in their total phospholipid levels per cell concomitant with a decrease in growth rate approaching minimal levels at stationary phase. Furthermore, the mole percentage of the supplemented unsaturated fatty acid in the cellular phospholipids also decreased during growth and attained minimal values when growth ceased. At stationary phase the total phospholipid content per cell was similar for cells grown on a wide range of fatty acids or mixtures thereof, whereas the composition of the fatty acids in the cellular phospholipids were strikingly different. The differences in efficiencies for supporting growth of most of the unsaturated fatty acids tested did not seem due to the extent of their corporation into cellular phospholipids, but rather to differences in the ability of the derived membrane phospholipids to support cellular functions. Palmitoleate, oleate, linoleate, linolenate, arachidonate, eicosapentaenoate, and docosahexaenoate all appeared to contribute to the functionality of cellular membranes in an additive linear manner. Thus, the contribution of these acids to cellular growth can be characterized by a functionality factor that seems independent of the mixtures of acids supporting growth. Use of the functionality concept allows the cumulative influence of many different acids to be summarized quantitatively by a single number rather than resorting to qualitative decriptions of the degree of unsaturation or 'fitness' of the membrane phospholipids.

Cell Division↗
PubMed1973

Quantitative measurement of the effectiveness of unsaturated fatty acids required for the growth of Saccharomyces cerevisiae.

The growth response of a mutant of Saccharomyces cerevisiae which is unable to synthesize unsaturated fatty acids has been measured in the presence of variable concentrations of exogenous unsaturated fatty acids. Final cell yields, doubling times, and lag times were all found to vary as a function of the initial concentration of the added unsaturated acid. The cell yield was found to be a convenient quantitative measurement to use in comparing the effectiveness of various unsaturated acids. Values for the acids ranged from 1.7 to 11 cells per femtomole with values for oleate and palmitoleate at 2.7 and 4.3 cells per femtomole, respectively. In general, the effectiveness of unsaturated acids was found to increase with an increasing number of double bonds. Saturated fatty acids of a chain length of 5 to 18 carbon atoms were completely ineffective. The varied efficiencies of different unsaturated fatty acids indicate that unsaturation per se was not the basis of the nutritional requirement and indicate certain acids that would be useful in further studies of the role of unsaturated acids in cell function.

Arachidonic Acids↗