Antibiotics as tools for metabolic studies. I. A survey of toxic antibiotics in respiratory, phosphorylative and glycolytic systems

Lardy, Henry A.; Johnson, Dale E.; McMurray, W. C.

doi:10.1016/0003-9861(58)90383-7

Cited by 732 publications

(173 citation statements)

References 11 publications

Supporting

Mentioning

162

Contrasting

Unclassified

Order By: Relevance

“…As fist shown by Lardy and associates [7], oligomycin is a specific inhibitor of phosphorylations coupled to the respiratory chain. It inhibits tightly-coupled respiration and the inhibition is released by uncouplers such as 2,4-dinitrophenol.…”

Section: Discussionmentioning

confidence: 81%

“…It also prevents the uncoupling of respiratory chain-linked phosphorylation caused by arsenate [35,36]. It inhibits furthermore the Pi-ATP [7] and Pi-H,O [12,13] exchange reactions.…”

Section: Discussionmentioning

confidence: 99%

“…I n particular various "nonphosphorylating" electron transport particle preparations [7], stimulates the respiratory chain-supported energy-linked transhydrogenase reaction in certain types of submitochondrial particles. This finding also was confirmed by others [5,6,8].…”

Section: Submitochondrial Particles Have In Recent Yearsmentioning

confidence: 99%

See 2 more Smart Citations

Studies of the Energy‐Transfer System of Submitochondrial Particles

Lee

Ernster

1968

European Journal of Biochemistry

178

View full text Add to dashboard Cite

1. Added in appropriate concentrations oligomycin stimulates oxidative phosphorylation and its reversal as well as Pi-ATP exchange in submitochondrial particles derived from beef heart mitochondria by sonication in the presence of EDTA. The optimal oligomycin concentration for these effects is in the range of 0.2-0.4 pglmg protein, above which concentration oligomycin is inhibitory. The optimal oligomycin concentration inhibits the ATPase reaction catalyzed by the same particles only by 20-25 2 . The maximal P/O ratio observed in the presence of oligomycin is approximately 1 with NADH, 0.8 with succinate, and 0.2 with ascorbate plus tetramethyl-p-phenylene diamine as substrate. Mgii, which is obligatory for the phosphorylation, lowers the P/O ratio when used in concentrations exceeding 2 mM. Oligomycin-stimulated reversal of oxidative phosphorylation also is Mg++ dependent, but insensitive to high Mgf+ concentrations. Oligomycins A, B, C, and D (rutamycin) are equally effective in exhibiting these effects, whereas aurovertin is ineffective and even abolishes the effects of oligomycin.3. Oligomycin does not stimulate phosphorylation in intact mitochondria or in submitochondrial particles prepared in the presence of ATP and Mg++. Optimal response with EDTA particles is obtained when these are sonicated in the presence of 2 mM EDTA a t pH 8.5-8.7.4. Oligomycin also induces a respiratory inhibition in EDTA particles which is relieved by uncouplers. The inhibition is 60-70 Olio in the case of NADH, and 40-50 O/, in the case of succinate as substrate. Little or no oligomycin-induced "respiratory control" is observed with ascorbate plus tetramethyl-p-phenylenediamine as substrate. The oligomycin-induced respiratory control does not require Mg++ and is diminished by the latter and by other divalent cations as well as certain anions. Aurovertin does not duplicate the effect of oligomycin in inducing respiratory control, and has no effect on the oligomycin-induced respiratory control or its relief by uncouplers. The "coupling factors" Fl, F4, and F,, alone or in combination, do not duplicate the effect of oligomycin in inducing "respiratory control" in these particles. 5. Oligomycin and aurovertin inhibit oxidative phosphorylation and Pi-ATP exchange in phosphorylating submitochondrial particles prepared in the presence of ATP and Mg++, and the effects of the two antibiotics on the P/O ratio are additive. I n contrast, aurovertin fails to inhibit the reversal of oxidative phosphorylation measured as ATP-supported succinate-linked NAD+ reduction, in Concentrations a t which oligomycin is completely inhibitory. At much higher concentrations aurovertin does inhibit the latter reaction, but the degree of inhibition decreases with time of incubation in the presence of ATP and Mg++.6. It is concluded that oligomycin acts on the respiratory chain-linked energy-transfer system of EDTA particles in two ways: a t low concentrations, it inhibits the hydrolytic cleavage of a nonphosphorylated high-energy intermediate, which is common...

show abstract

Section: Discussionmentioning

confidence: 81%

“…It also prevents the uncoupling of respiratory chain-linked phosphorylation caused by arsenate [35,36]. It inhibits furthermore the Pi-ATP [7] and Pi-H,O [12,13] exchange reactions.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Studies of the Energy‐Transfer System of Submitochondrial Particles

Lee

Ernster

1968

European Journal of Biochemistry

178

View full text Add to dashboard Cite

show abstract

“…Oligomycin is an antibiotic that inhibits oxidative phosphorylation in mitochondria (Lardy et al 1958;Huijing & Slater, 1961). It also inhibits the sodium pump in red blood cells in which there are no mitochondria, thus raising the possibility that it may also be an inhibitor of the sodium pump in cells that do contain mitochondria (Glynn, 1963;).…”

Section: The Action Of Oligomycinmentioning

confidence: 99%

“…In order to ascertain whether the special features of brain cortex fit this general notion, which attributes a key role to sodium ions, slices have been incubated in Ringer solution under conditions that facilitate or inhibit the sodium pump. Oligomycin was used as an inhibitor, because it acts in red cells like ouabain (Whittam, Wheeler & Blake, 1964), and yet is also an inhibitor of oxidative phosphorylation in respiring cells (Lardy, Johnson & McMurray, 1958;Huijing & Slater, 1961). It was found to be unlike ouabain in its effects on brain cortex slices.…”

Section: Introductionmentioning

confidence: 99%

The metabolic response of brain slices to agents affecting the sodium pump

Ruscák¹,

Whittam²

1967

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. Slices of brain cortex from rabbits were incubated in Ringer solution and in Ringer modified by the removal of calcium and sodium, and the addition of ouabain, oligomycin or extra potassium. The potassium content of the tissue, the oxygen consumption and the lactate production from glucose were measured and found to be interrelated.2. Incubation in high-K Ringer caused an increase in oxygen consumption that was prevented by ouabain, oligomycin and deprivation of sodium. Lactate production was also raised, but this increase was unaffected by ouabain and raised further by oligomycin.3. Calcium omission raised metabolism; the tissue K content was unaffected. Oligomycin always decreased oxygen consumption and raised lactate production further. The metabolic responses to calcium, potassium, ouabain and oligomycin depended on sodium.4. After anaerobic incubation, the tissue potassium concentration was still 5 times higher than that in Ringer. It was unaffected by oligomycin but lowered markedly by ouabain.5. The synergistic effects of sodium with potassium, oligomycin, calcium, and calcium plus ouabain suggest that the metabolic responses of brain cortex slices to a high-K Ringer depend on the operation of the sodium pump.

show abstract

Interference of Cadmium Ion With Oxidative Metabolism of Alveolar Macrophages

Mustafa¹

1971

Arch Intern Med

View full text Add to dashboard Cite

show abstract

Antibiotics as tools for metabolic studies. I. A survey of toxic antibiotics in respiratory, phosphorylative and glycolytic systems

Cited by 732 publications

References 11 publications

Studies of the Energy‐Transfer System of Submitochondrial Particles

Studies of the Energy‐Transfer System of Submitochondrial Particles

The metabolic response of brain slices to agents affecting the sodium pump

Interference of Cadmium Ion With Oxidative Metabolism of Alveolar Macrophages

Contact Info

Product

Resources

About