How does oligomycin affect cellular respiration?
Oligomycin prevents the increase in mitochondrial respiration induced by ADP without inhibiting uncoupler-stimulated respiration. NADH remains high and NAD+ is too low for the citric acid cycle to operate.
How does oligomycin affect cellular respiration and ATP synthesis?
Oligomycin A inhibits ATP synthase by blocking its proton channel (FO subunit), which is necessary for oxidative phosphorylation of ADP to ATP (energy production). This process is due to facilitated diffusion of protons into the mitochondrial matrix through an uncoupling protein such as thermogenin, or UCP1.
How was Oligomycin a discovered?
It is synthesized in 1986 in Manchester, England. The researchers used simple carbon compounds (acetate, butyrate and propionate) labelled with carbon-13, fed these to the cells then extracted the oligomycin and looked at where the carbon-13 atoms were.
Can oligomycin cause death?
Oligomycin, an inhibitor of the reversible mitochondrial ATP synthase (F1F0-adenosinetriphosphatase), caused dose-dependent cell killing with 0.1 microgram/ml being the minimum concentration causing the maximum cell killing. Fructose retarded cell death caused by CCCP but failed to prevent lethal cell injury.
Where is Oligomycin found?
Oligomycin is a group of Streptomyces macrolides that bind to the Oligomycin sensitivity-conferring protein (OSCP) at the F(o) subunits 6 and 9 which are found in the stalk of the F1F0-ATPase complex. This binding blocks proton conductance across the synthase complex and inhibits the synthesis of mitochondrial ATP.
Where is oligomycin found?
How is the biosynthetic pathway to ossamycin identified?
Analysis of a near-com- plete genome sequence of the ossamycin producer has allowed the identification of the 127-kbp ossamycin biosynthetic gene cluster. The presence in the cluster of a specific cro-
Are there any macrocyclic polyketides related to oligomycin?
Various other macrocyclic polyketides related to the oligomycins/ rutamycins have been isolated (Fig 1) by screening for antifungal, immunosuppressive or cyto- toxic bioactivity, including for example the 24-membered dunaimycins , and the 22-mem- bered cytovaricin , A82548A (also known as yokonolide B) , yokonolide A ,
What makes up the macrocyclic core of ossamycin?
The presence in the cluster of a specific cro- tonyl-CoA carboxylase/reductase homologue suggests that the 5-methylhexanoate exten- sion unit used in construction of the macrocyclic core is incorporated intact from the unusual precursor isobutyrylmalonyl-CoA.