scholarly journals The manipulation of cellular cytochrome and lipid composition in a haem mutant of Saccharomyces cerevisiae

1977 ◽  
Vol 166 (2) ◽  
pp. 275-285 ◽  
Author(s):  
A M Astin ◽  
J M Haslam

1. The ole-3 mutant of Saccharomyces cerevisiae has an early lesion in the pathway of porphyrin biosynthesis. 2. This results in the loss of all haem-containing enzymes, including the mitochondrial cytochromes, and prevents the synthesis of components whose formation requires haem-containing enzymes, including unsaturated fatty acids, ergosterol and methionine. 3. The pleiotropic effects of the primary lesion are reversed by growing mutant ole-3 aerobically in the presence of intermediates of the porphyrin-biosynthetic pathway, and the present work reports the degree of manipulation of lipid and respiratory-cytochrome composition. 4. Supplements of delta-aminolaevulinate in the range 0.5–500 mg/l result in a progressive increase in the cellular content of unsaturated fatty acids and respiratory cytochromes, cause the replacement of lanosterol and squalene by ergosterol, and an increase in total sterol content. 5. Haematoporphyrin and protoporphyrin IX have similar but less extensive effects on cellular composition, whereas haematin allows unsaturated fatty acid synthesis and some sterol synthesis, but has no effect on the formation of respiratory cytochromes. 6. These results suggest that growth of the organism in the presence of defined amounts of delta-aminolaevulinate will be useful in the investigation of the role of lipids and cytochromes in the function and assembly of mitochondrial membranes.

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i19-i19
Author(s):  
Divya Ravi ◽  
Carmen del Genio ◽  
Haider Ghiasuddin ◽  
Arti Gaur

Abstract Glioblastomas (GBM) or Stage IV gliomas, are the most aggressive of primary brain tumors and are associated with high mortality and morbidity. Patients diagnosed with this lethal cancer have a dismal survival rate of 14 months and a 5-year survival rate of 5.6% despite a multimodal therapeutic approach, including surgery, radiation therapy, and chemotherapy. Aberrant lipid metabolism, particularly abnormally active de novo fatty acid synthesis, is recognized to have a key role in tumor progression and chemoresistance in cancers. Previous studies have reported a high expression of fatty acid synthase (FASN) in patient tumors, leading to multiple investigations of FASN inhibition as a treatment strategy. However, none of these have developed as efficacious therapies. Furthermore, when we profiled FASN expression using The Cancer Genome Atlas (TCGA) we determined that high FASN expression in GBM patients did not confer a worse prognosis (HR: 1.06; p-value: 0.51) and was not overexpressed in GBM tumors compared to normal brain. Therefore, we need to reexamine the role of exogenous fatty acid uptake over de novofatty acid synthesis as a potential mechanism for tumor progression. Our study aims to measure and compare fatty acid oxidation (FAO) of endogenous and exogenous fatty acids between GBM patients and healthy controls. Using TCGA, we have identified the overexpression of multiple enzymes involved in mediating the transfer and activation of long-chain fatty acids (LCFA) in GBM tumors compared to normal brain tissue. We are currently conducting metabolic flux studies to (1) assess the biokinetics of LCFA degradation and (2) establish exogenous versus endogenous LCFA preferences between patient-derived primary GBM cells and healthy glial and immune cells during steady state and glucose-deprivation.


2000 ◽  
Vol 113 (3) ◽  
pp. 533-544
Author(s):  
I.V. Karpichev ◽  
G.M. Small

We, and others, have identified a novel Saccharomyces cerevisiae peroxisomal protein that belongs to the isomerase/hydratase family. The protein, named Dci1p, shares 50% identity with Eci1p, a delta(3)-cis-delta(2)-trans-enoyl-CoA isomerase that acts as an auxiliary enzyme in the beta-oxidation of unsaturated fatty acids. Both of these proteins are localized to peroxisomes, and both contain motifs at their amino- and carboxyl termini that resemble peroxisome targeting signals (PTS) 1 and 2. However, we demonstrate that the putative type 1 signaling motif is not required for the peroxisomal localization of either of these proteins. Furthermore, the correct targeting of Eci1p and Dci1p occurs in the absence of the receptors for the type 1 or type 2 peroxisome targeting pathway. Together, these data suggest a novel mechanism for the intracellular targeting of these peroxisomal proteins.


1961 ◽  
Vol 39 (4) ◽  
pp. 739-746 ◽  
Author(s):  
Frank Sauer

Non-diabetic ketosis was produced experimentally in fasted pregnant guinea pigs. Total CO2output of ketotic animals was less than that of appropriate controls but there was no impairment in the conversion of acetate-1-C14to C14O2. Sterol synthesis increased in ketotic animals while fatty acid synthesis, particularly in carcass, showed the expected decrease. Ketosis was accompanied by an increase in plasma total fatty acids and in the fatty acid concentration of liver. The experimental findings support the hypothesis that ketosis is a manifestation of increased ketogenesis rather than impaired utilization of ketone bodies.


2010 ◽  
Vol 76 (9) ◽  
pp. 2989-2996 ◽  
Author(s):  
Juan Zhang ◽  
Guo-Cheng Du ◽  
Yanping Zhang ◽  
Xian-Yan Liao ◽  
Miao Wang ◽  
...  

ABSTRACT Lactobacillus sanfranciscensis DSM20451 cells containing glutathione (GSH) displayed significantly higher resistance against cold stress induced by freeze-drying, freeze-thawing, and 4°C cold treatment than those without GSH. Cells containing GSH were capable of maintaining their membrane structure intact when exposed to freeze-thawing. In addition, cells containing GSH showed a higher proportion of unsaturated fatty acids in cell membranes upon long-term cold treatment. Subsequent studies revealed that the protective role of GSH against cryodamage of the cell membrane is partly due to preventing peroxidation of membrane fatty acids and protecting Na+,K+-ATPase. Intracellular accumulation of GSH enhanced the survival and the biotechnological performance of L. sanfranciscensis, suggesting that the robustness of starters for sourdough fermentation can be improved by selecting GSH-accumulating strains. Moreover, the results of this study may represent a further example of mechanisms for stress responses in lactic acid bacteria.


FEBS Letters ◽  
2005 ◽  
Vol 579 (23) ◽  
pp. 5157-5162 ◽  
Author(s):  
Chang Ji Zheng ◽  
Jung-Sung Yoo ◽  
Tae-Gyu Lee ◽  
Hee-Young Cho ◽  
Young-Ho Kim ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document