Oxidative Phosphorylation: A Role for Lipoic Acid and Unsaturated Fatty Acids

1977 ◽  
Vol 5 (1) ◽  
pp. 207-208 ◽  
Author(s):  
DAVID E. GRIFFITHS ◽  
ROBERT L. HYAMS
1976 ◽  
Vol 160 (3) ◽  
pp. 809-812 ◽  
Author(s):  
D E Griffiths

ATP synthase preparations [complex V, proton-translocatin ATPase (adenosine triphosphatase) and oligomycin-sensitive ATPase] contain stoicheiometric amounts of lipoic acid residues (up to 6mol of lipoic acid/mol of ATPase complex) and catalyse net ATP synthesis in an uncoupler-and oligomycin-sensitive reaction utilizing dihydrolipoate, oleoyl-CoA and oleic acid, or in a reaction utilizing oleoyl-S-lipoate. The terminal reactions of oxidative phosphorylation are thus analogous to those of substrate-level phosphorylation.


1973 ◽  
Vol 134 (4) ◽  
pp. 949-957 ◽  
Author(s):  
J. M. Haslam ◽  
T. W. Spithill ◽  
Anthony W. Linnane ◽  
J. B. Chappell

1. The fatty acid composition of the membrane lipids of a fatty acid desaturase mutant of Saccharomyces cerevisiae was manipulated by growing the organism in a medium containing defined fatty acid supplements. 2. Mitochondria were obtained whose fatty acids contain between 20% and 80% unsaturated fatty acids. 3. Mitochondria with high proportions of unsaturated fatty acids in their lipids have coupled oxidative phosphorylation with normal P/O ratios, accumulate K+ ions in the presence of valinomycin and an energy source, and eject protons in an energy-dependent fashion. 4. If the unsaturated fatty acid content of the mitochondrial fatty acids is lowered to 20%, the mitochondria simultaneously lose active cation transport and the ability to couple phosphorylation to respiration. 5. The loss of energy-linked reactions is accompanied by an increased passive permeability of the mitochondria to protons. 6. Free fatty acids uncouple oxidative phosphorylation in yeast mitochondria and the effect is reversed by bovine serum albumin. 7. The free fatty acid contents of yeast mitochondria are unaffected by depletion of unsaturated fatty acids, and free fatty acids are not responsible for the uncoupling of oxidative phosphorylation in organelles depleted in unsaturated fatty acids. 8. It is suggested that the loss of energy-linked reactions in yeast mitochondria that are depleted in unsaturated fatty acids is a consequence of the increased passive permeability to protons, and is caused by a change in the physical properties of the lipid phase of the inner mitochondrial membrane.


2009 ◽  
Vol 191 (24) ◽  
pp. 7447-7455 ◽  
Author(s):  
Natalia Martin ◽  
Esteban Lombardía ◽  
Silvia G. Altabe ◽  
Diego de Mendoza ◽  
María C. Mansilla

ABSTRACT Lipoic acid is an essential cofactor required for the function of key metabolic pathways in most organisms. We report the characterization of a Bacillus subtilis mutant obtained by disruption of the lipA (yutB) gene, which encodes lipoyl synthase (LipA), the enzyme that catalyzes the final step in the de novo biosynthesis of this cofactor. The function of lipA was inferred from the results of genetic and physiological experiments, and this study investigated its role in B. subtilis fatty acid metabolism. Interrupting lipoate-dependent reactions strongly inhibits growth in minimal medium, impairing the generation of branched-chain fatty acids and leading to accumulation of copious amounts of straight-chain saturated fatty acids in B. subtilis membranes. Although depletion of LipA induces the expression of the Δ5 desaturase, controlled by a two-component system that senses changes in membrane properties, the synthesis of unsaturated fatty acids is insufficient to support growth in the absence of precursors for branched-chain fatty acids. However, unsaturated fatty acids generated by deregulated overexpression of the Δ5 desaturase functionally replaces lipoic acid-dependent synthesis of branched-chain fatty acids. Furthermore, we show that the cold-sensitive phenotype of a B. subtilis strain deficient in Δ5 desaturase is suppressed by isoleucine only if LipA is present.


1977 ◽  
Vol 166 (2) ◽  
pp. 287-298 ◽  
Author(s):  
Anne M. Astin ◽  
J. M. Haslam

1. The sterol, unsaturated fatty acid and cytochrome contents of cells of a δ-aminolaevulinate synthase mutant of Saccharomyces cerevisiae are manipulated by growing the organism in media containing defined supplements of δ-aminolaevulinate and other porphyrin intermediates. 2. If unsaturated fatty acids are added to the growth medium as Tween 80, sterol content and respiratory cytochromes alone are manipulated. 3. In the presence of δ-aminolaevulinate (10–50mg/1) cells exhibit moderate to high respiratory activity, but growth yields are low, indicating a loss of oxidative phosphorylation. This is associated with the depletion of membrane lipids, either unsaturated fatty acids and sterols together or sterols alone. 4. Sterol depletion leads to the loss of coupled mitochondrial oxidative phosphorylation in vitro. 5. The lesion in oxidative phosphorylation is associated with an increase in the passive permeability of sterol-depleted mitochondria to protons. 6. Arrhenius plots of mitochondrial permeability to protons indicate that the activation energy for proton entry increases as the sterol content of the membranes decreases. 7. Studies on a cytoplasmic petite mutant isolated from strain ole-3, which lacks a functional membrane-bound protein-translocating adenosine triphosphatase, indicate that proton permeability of the petite mitochondria varies as a function of sterol composition in the same way as that of ole-3 grande mitochondria. This indicates that sterols alone are probably directly responsible for the increased proton entry, owing to a reorganization of the lipid in the membrane. 8. Supplemented ole-3 cells with a normal lipid composition and normal or higher than normal respiratory activities have a growth efficiency only 65% of that of the wild-type, indicating that a further lesion in energy metabolism may be present.


2020 ◽  
Vol 20 (2) ◽  
pp. 38-40
Author(s):  
A. Levitsky ◽  
A. Lapinska ◽  
I. Selivanskaya

The article analyzes the role of essential polyunsaturated fatty acids (PUFA), especially omega-3 series in humans and animals. The biosynthesis of essential PUFA in humans and animals is very limited, so they must be consumed with food (feed). Тhe ratio of omega-3 and omega-6 PUFA is very important. Biomembranes of animal cells contain about 30% PUFA with a ratio of ω-6/ ω-3 1-2. As this ratio increases, the physicochemical properties of biomembranes and the functional activity of their receptors change. The regulatory function of essential PUFA is that in the body under the action of oxygenase enzymes (cyclooxygenase, lipoxygenase) are formed extremely active hormone-like substances (eicosanoids and docosanoids), which affect a number of physiological processes: inflammation, immunity, metabolism. Moreover, ω-6 PUFA form eicosanoids, which have pro-inflammatory, immunosuppressive properties, and ω-3 PUFAs form eicosanoids and docosanoids, which have anti-inflammatory and immunostimulatory properties. Deficiency of essential PUFA, and especially ω-3 PUFA, leads to impaired development of the body and its state of health, which are manifestations of avitaminosis F. Prevention and treatment of avitaminosis F is carried out with drugs that contain PUFA. To create new, more effective vitamin F preparations, it is necessary to reproduce the model of vitamin F deficiency. An experimental model of vitamin F deficiency in white rats kept on a fat –free diet with the addition of coconut oil, which is almost completely free of unsaturated fatty acids, and saturated fatty acids make up almost 99 % of all fatty acids was developed. The total content of ω-6 PUFA (sum of linoleic and arachidonic acids), the content of ω-3 PUFA (α-linolenic, eicosapentaenoic and docosahexaenoic acids) in neutral lipids (triglycerides and cholesterol esters) defined. Тhe content of ω-6 PUFA under the influence of coconut oil decreased by 3.3 times, and the content of ω-3 PUFA - by 7.5 times. Тhe influence of coconut oil, the content of ω-6 PUFA decreased by 2.1 times, and the content of ω-3 PUFA - by 2.8 times. The most strongly reduces the content of ω-3 PUFA, namely eicosapentaenoic, coconut oil, starting from 5 %. Consumption of FFD with a content of 15 % coconut oil reduces the content of eicosapentaenoic acid to zero, ie we have an absolute deficiency of one of the most important essential PUFAs, which determined the presence of vitamin F deficiency.


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