Regulatory Mechanisms of Cellular Respiration

Abstract

The large number of inhibitors of cellular respiration hitherto described have been reported to act by inhibiting the activity of enzyme systems. They do so (1) by combining with the activating protein, either through some groups essential for activity (for example, the -S H groups), through denaturation of the molecule, or by combination on the side chains where substrates or prosthetic groups form the protein-substrate complex (structural inhibitors); (2) by combining with the prosthetic groups of enzymes (diphosphothiamine, pyridoxal, pantothenic acid, etc.); (3) by combining with the series of oxidation reduction systems (pyridine nucleotides, flavins, cytochromes) which transfer electrons from oxidizable substrate to molecular oxygen. Besides this direct action on the components of enzyme systems, cellular respiration may be affected by alteration of the varied mechanisms which regulate in the living cells the rate and the direction of enzymatic reactions. One of these regulating mechanisms is the state of the cellular membrane. It is generally agreed that the cell membrane is a lipoid-protein system possessing varying degrees of permeability where penetration occurs by passage through the pores of the membrane or through solution in the lipoid portion. Any alteration of the solubility coefficient in the lipoid phase or changes of the pore size will bring forth alterations in the rate of passage of substrates, and as a consequence alterations in the metabolsim of the cell. We present in this paper experiments on the inhibition of cellular oxidations produced by uranyl nitrate, which have been interpreted as being due to combination of uranium with the protein layer of the cell membrane, bringing thus an increased impermeability to the passage of certain oxidizable substrates. EXPERIMENTALThe yeast cells used in these experiments were brewers' yeast from Keely Brewing Company, Chicago, and bakers' yeast from Fleischmann. The first fermented

Association of uranyl with the cell wall of Pseudomonas fluorescens inhibits metabolism

“…An early study (Barron et al, 1948) documented the toxic effect of uranyl on yeast and bacteria, including Pseudomonas aeruginosa. Kelly (1974a, 1974b) also recorded the toxic effect of uranyl on the iron oxidizer Thiobacillus ferrooxidans at acidic pH.…”

Localization of Crystals in Diseased Oats Treated with Uranyl Acetate

“…Rothstein (10) also has shown that uranyl salts do not readily penetrate yeast cells and instead are bound firmly to the cell wall. Barron et al (1) concluded that uranyl salts do not penetrate cells of yeast, Escherichia coli, or sea urchin sperm. The inhibitions of respiration observed in cells treated with uranyl nitrate were apparently not caused by direct reaction with respiratory enzymes, but instead were interpreted to result from a combination of uranium with the cell membrane with a consequent decrease in permeability to selected oxidizable substrates.…”

“…Even if binding of uranyl to the toxin could be demonstrated, the conclusion that victorin is inactivated may be an oversimplification. Binding of uranyl to proteins, with consequent inhibition of enzymatic activity, has been shown by Barron et al (1) to be reversible.…”

Targeted delivery of bio-active molecules to mitochondria using mesoporous silica nanoparticles for anti-cancer applications

“…Such energy production process mainly occurs in the inner membrane. It is generally accepted that there are two major types of cellular respiration [17][18][19][20][21] . The first type is called aerobic respiration, which happens when in the presence of oxygen.…”