2,4-Dinitrophenol metabolism inhibitor

Many substances inhibit slow channel transport. In addition to the divalent cations already cited (Mn +, Co + and Ni +), protons, La3+, the metabolic inhibitors cyanide and dinitrophenol, are effective inhibitors (24). Other inhibitory agents include acetylcholine, (42) papaverine, (43) pentobarbital, lidoflazine, (44) and adenosine (45) as well as verapamil, nifedipine and diltiazem (1). Precisely how many of these substances interfere with slow channel transport is unknown, although in the case of the metabolic inhibitors we can probably account for their effect in terms of the energy requirements (24) needed for maintaining the configurational state of the cell membrane compatible with the maintenance of normal slow channel ultrastructure. 

Only a few enzymes are specifically secreted by organs into the blood stream. These are the enzymes of blood coagulation, cholinesterase, and amylase [21]. Serum, in the main, is a passive receptacle for enzymes derived from the tissue cells and the formed elements of blood. Normally, the level of enzymes in serum is both low and constant. Since most of the enzymes present are derived from cells, it follows that these enzymes must be able to pass through the limiting membrane of the parent cell. This outward passage is accomplished either by diffusion through pores or alternatively by the aid of an active transport system. Except in those cases where enzyme secretion is a physiological process, active transport is unlikely. The loss of enzymes from cells is accelerated by tissue injury, and also by metabolic inhibitors like 2,4-dinitrophenol, iodoacetate, and carbon monoxide [22]. The implication that the retention by the cell of a... 

P, They were then incubated in similar medium for electrical stimulation as described above. In some experiments 2 mM 2,4-dinitrophenol and 10 mM 2-deoxyglucose were added to block further synthesis of phospholipids. Electrical stimulation for 10 min at 100 Hz produced a marked loss of labelled phosphatidate and phosphatidylinositol from the synaptosomes, In the presence of the metabolic inhibitors more than 90% of the phosphatidate radioactivity was lost. The corresponding figure for phosphatidylinositol was 60%,... 

The rate of uptake is temperature-dependent, with a Qio of about 2-0. Uptake is relatively resistant to metabolic inhibitors, such as cyanide, iodoacetate, and dinitrophenol, or to anoxia or lack of glucose. However, if both aerobic and anaerobic energy metabolism is inhibited, the uptake of exogenous catecholamines is blocked. This indicates that the energy needed to transport the very small amounts of catecholamine can be provided by either aerobic or anaerobic metabolism. 

The entry of lysine into either Staph, aureus or Strep, faecalis is unaffected by the presence of common metabolic inhibitors such as cyanide, iodoacetate, fluoride, azide or 2,4-dinitrophenol. Cells in which the accumulation of glutamic acid has been prevented by growth in the presence of penicillin, are able to accumulate lysine to the normal extent (Gale and Taylor, 1947b). 

Most of the reports on the effects of HA on the nutrient contents of plants are purely descriptive and little attempt was made in the earlier work to elucidate the mechanisms of the action of the humic material. The final concentration of a nutrient in a plant can depend on a number of factors such as the concentration in the nutrient solution, its interactions with other nutrients and/or humic substances, the pH of the nutrient medium in addition to the effects of the humic substances on the ion uptake mechanism and finally translocation within the plant. Several of these factors are well illustrated in a recent paper by Guminski e al. These workers showed for example that Mg is taken up to a greater extent at pH 5.0 than at pH 7.0 and that, in general, humate stimulated Mg uptake at both pH values. Guminski e a also demonstrated that the metabolic inhibitor 2,4-dinitrophenol had an adverse effect on any stimulation of ion uptake produced by HA. Such a result demonstrates that humates can influence nutrient concentration in plants directly through metabolic processes. 

Protonophores such as carbonyl cyanide trifluoromethoxyphenyl hydrazone (FCCP) and 2,4-dinitrophenol (2,4-DNP) and metabolic inhibitors such as sodium azide are also known to inhibit these membrane redox systems (39, 57). Protonophores act by dissipating the proton motive force at the membrane which at low concentrations actually stimulates electron flow across membranes (4,22). A slight stimulation in TNT reduction was observed with FCCP, between 0 and 50 pM, but was not statistically significant. In general, TNT reduction was inhibited by these compounds at concentrations known to inhibit membrane redox systems. 

To see whether active transport of the quaternary nitrogen compounds outwards through the BBB or BRB could play any role in these events, similar experiments were performed on two groups of animals pretreated with inhibitors of metabolism-dependent transport, viz., 2,4-dinitrophenol and ouabain. In some additional ex-... 

Monoamine oxidase inhibitors Phencyclidine Tricyclic antidepressants Increased metabolic rate Dinitrophenol and pentachlorophenol Salicylates Thyroid hormone... 

Dantrolene is not likely to be effective for hyperthennia caused by conditions other than muscular hyperactivity, such as increased metabolic rate (eg, salicylate or dinitrophenol poisoning), neuroleptic malignant syndrome (NMS), impaired heat dissipation (eg, anticholinergic syndrome), or environment exposure (heat stroke). However, there is anecdotal evidence (case reports or case-control studies) of benefit for the management of NMS, MAO inhibitor (phenelzine poisoning)-induced hyperthermia, muscle rigidity from baclofen withdrawal, hypertonicity from carbon monoxide poisoning, tetanus, and black widow spider envenomation. 

While the role df lipids in protein s mthesis has not been clarified, there have been reports of a number of different amino acid-lipid complexes. Hendler 93) has investigated in further detail the metabolically active amino acid-lipid compounds which are rapidly formed in intact cells of hen oviduct. By means of countercurrent distribution and chromatography on columns of aliunina-silica and of silicic acid, he has been able to demonstrate a large number of these compounds. These, furthermore, show a distribution pattern which can be altered in a typical fashion by inhibitors, such as dinitrophenol. Lipid-amino acid complexes similar to those in hen oviduct were also found to be present in the membranes and crude ribosome fraction of E. coli. 

Inhibition of protein, RNA, and DNA synthesis by herbicides has been the subject of numerous reports and reviews (see, e.g.. Refs. 3, 4, and 137-139). Inhibition of the biosynthesis of any of these macromolecules would lead to an effective and abrupt cessation of plant growth. However, with very few exceptions, the reports on herbicidal interference with protein and nucleic acid synthesis reflect secondary effects resulting from an effect at a target site elsewhere in the cell. For example, any interruption of the production of metabolic energy, as a result of respiratory uncoupling and/or inhibition, would lead to a rapid cessation of macromolecular synthesis. In several surveys of herbicide effects on C-labeled precursor incorporation into protein and RNA in excised plant tissues and isolated mesophyll cells, dinitrophenols and hydroxybenzonitriles were the most potent inhibitors (Section 5.1 see, e.g.. Refs. 138 and 140). 

---