The respiratory chain and oxidative phosphorylation are of utter importance for a cell’s metabolism. Here, the energy won from ingested food is being converted into our body’s energy unit (adenosine triphosphate). As the name respiratory chain suggests, oxygen also plays an important role. The following article will explain how exactly this complex mechanism works and which substances may disable it.

The respiratory chain and oxidative phosphorylation.

Publisher Summary This chapter provides a framework for understanding the way permanent heritable damage in cellular DNA results from exposure to ionizing radiation. If the processes that occur in the time between the initial radiation energy deposition and the formation of such damage can be described, then rationales can be developed for the modulation of radiation damage. For example, it may be possible to (1) devise a means of differentially modulating the amounts of radiation damage, for instance, in tumor versus normal tissue in radiotherapy, or (2) predict the effects of variations of several parameters on the biological consequences of a radiation dose. It has been concluded that the types and yields of damaged moieties produced in intracellular DNA by low LET ionizing radiation are consistent with the mechanisms of production that involve both OH radical attack and a direct ionization of the macromolecule. At the radiation-dose levels producing one lethal lesion per cell, the amounts of damage produced by ionizing radiation are several orders of magnitude lower than the amounts of damage required for equal kill by other agents. Individual damaged moieties are not biologically significant; they can easily be repaired using the undamaged DNA strand as a template. The lethal lesion produced in cellular DNA is a locally multiply damaged site.

DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation, and reparability.

Recombinant DNA technology has now made it possible to produce proteins for pharmaceutical applications Consequently, proteins produced via biotechnology now comprise a significant portion of the drugs currently under development Isolation, purification, formulation, and delivery of proteins represent significant challenges to pharmaceutical scientists, as proteins possess unique chemical and physical properties These properties pose difficult stability problems A summary of both chemical and physical decomposition pathways for proteins is given Chemical instability can include proteolysis, deamidation, oxidation, racemization, and β-elimination Physical instability refers to processes such as aggregation, precipitation, denaturation, and adsorption to surfaces Current methodology to stabilize proteins is presented, including additives, excipients, chemical modification, and the use of site-directed mutagenesis to produce a more stable protein species

Stability of Protein Pharmaceuticals

Three categories of phosphatase activity toward adenosine triphosphate at pH 9.4 have been isolated histochemically: (1) phosphatase which requires -SH groups; (2) phosphatase which is inhibited by -SH groups; and (3) phosphatase which is relatively indifferent to -SH groups. This enzymatic activity was demonstrated in thin (5 µ), unfixed, frozen sections.True adenosine triphosphatase has been separated histochemically by virtue of its -SH dependence. It was demonstrated in cardiac and skeletal muscle fibers and in the mitochondria of the kidney tubules. The staining of these structures can be prevented by treatment with an -SH inhibitor, such as p-chloromercuribenzoate or salyrganic acid. Also their stainability can be restored by reversing the inhibition of the enzymes with -SH compounds, such as BAL or cysteine. There was no reaction of these particular structures when adenosine diphosphate or adenosine-5-phosphate was used, suggesting that under the conditions of this histochemical test only the termi...

The specificity of the histochemical method for adenosine triphosphatase.

The Determination of Nucleic Acids

Studies on biological oxidations: xix. sulfhydryl enzymes in carbohydrate metabolism

Dilute solutions of sulfhydryl enzymes (phosphoglyceraldehyde dehydrogenase, adenosinetriphosphatase, succinoxidase) showed reduced activity on irradiation by small amounts of x-rays. When the inhibition was partial the enzyme was reactivated on addition of glutathione. When the inhibition was more complete, reactivation was only partial. These observations are interpreted as being due to oxidation of the -SH groups of the protein by the products of water irradiation, the radicals OH and O(2)H, and H(2)O(2) and atomic oxygen. The irreversible inhibition which occurs when the dose of x-rays is increased is attributed to protein denaturation. Inhibition of the non-sulfhydryl enzymes trypsin, catalase, and ribonuclease, which required larger amounts of x-rays, is attributed to protein denaturation. These experiments are further evidence that inhibition of enzymes by ionizing radiations is due to the indirect action of the products of irradiated water rather than to direct ionization of the enzyme through collision with the ionizing radiation.

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Studies on the mechanism of action of ionizing radiations i. inhibition of enzymes by x-rays

Studies on biological oxidations v. copper and hemochromogens as catalysts for the oxidation of ascorbic acid. the mechanism of the oxidation

Thiol compounds, such as glutathione, 2,3-dimercaptopropanol (BAL), propane-1,3-dithiol, and N-phenylaminopropanedithiol, were readily oxidized by x-rays, beta rays, and gamma rays. The ionic yield for this oxidation was about the same, 3 at pH 7, on irradiation with x-rays and with beta rays; it was 23 per cent less on irradiation with gamma rays. The ionic yield varied with the hydrogen ion concentration, increasing as the pH value increased. There was no reduction of oxidized glutathione on irradiation with dosages of x-rays and gamma rays which produced oxidation of the reduced compound. In the absence of oxygen, the oxidation of thiols by ionizing radiations was only 33 per cent of that obtained in the presence of dissolved oxygen. When the thiol solutions were irradiated in the presence of dissolved oxygen, catalase protected them from oxidation by 17 to 27 per cent.

https://rupress.org/jgp/article-pdf/33/3/229/1399002/229.pdf

E. S. Guzman Barron

Papers

Studies on biological oxidations: xix. sulfhydryl enzymes in carbohydrate metabolism

Studies on the mechanism of action of ionizing radiations i. inhibition of enzymes by x-rays

Studies on biological oxidations v. copper and hemochromogens as catalysts for the oxidation of ascorbic acid. the mechanism of the oxidation

Studies on the mechanism of action of ionizing radiations : vi. the oxidation of thiols by ionizing radiations

Studies on biological oxidations xx. sulfhydryl enzymes in fat and protein metabolism