Physical mechanism for inactivation of metallo-enzymes by characteristic X-rays: analysis of the data of Jawad and Watt. 1987

D T Goodhead, and H Nikjoo
Medical Research Council Radiobiology Unit, Didcot, Oxfordshire, U.K.

Table 1 summarizes the mean numbers of events and interactions of various types which we calculate to occur per single dihydro-orotic dehydrogenase enzyme when irradiated in solution with D37 = 99 Gy of 8.04 keV X-rays under the experimental conditions of Jawad and Watt (1986). There are clearly many orders or magnitude too few direct interactions of X-ray photons, or electrons, with the enzymes for these processes to be responsible for the mean of one inactivating event per enzyme which must occur at the D37 dose. Jawad and Watt (1986) concluded that the enzyme inactivation was predominantly due to direct interaction of an X-ray photon with a non-metal atom of the enzyme, but our analysis shows that this is not possible by five orders of magnitude. Of the possible mechanisms (a)-(d), the only one which remains feasible in this experimental system is the indirect action of radiolysis products from the solution (d). Diffusion distances of the order of 0.1 micron may be quite adequate for such inactivation. The situation would be very different for enzymes or other molecules within mammalian cells where diffusion distances are very much smaller (probably of the order of a few nanometres). Our analysis leaves unexplained the fairly small (20 per cent) change in effectiveness reported by Jawad and Watt (1986) for X-ray energy above, as compared to below, the K-absorption edge of Fe. The experimental observation is directly dependent on the accuracy of the dosimetry at these two energies; we have made no attempt to evaluate this.

UI MeSH Term Description Entries
D008667 Metalloproteins Proteins that have one or more tightly bound metal ions forming part of their structure. (Dorland, 28th ed) Metalloprotein
D010088 Oxidoreductases The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9) Dehydrogenases,Oxidases,Oxidoreductase,Reductases,Dehydrogenase,Oxidase,Reductase
D011827 Radiation Emission or propagation of acoustic waves (SOUND), ELECTROMAGNETIC ENERGY waves (such as LIGHT; RADIO WAVES; GAMMA RAYS; or X-RAYS), or a stream of subatomic particles (such as ELECTRONS; NEUTRONS; PROTONS; or ALPHA PARTICLES). Radiations
D004081 Dihydroorotate Oxidase An enzyme that in the course of pyrimidine biosynthesis, catalyzes the oxidation of dihydro-orotic acid to orotic acid utilizing oxygen as the electron acceptor. This enzyme is a flavoprotein which contains both FLAVIN-ADENINE DINUCLEOTIDE and FLAVIN MONONUCLEOTIDE as well as iron-sulfur centers. EC 1.3.3.1. Dihydro-Orotate Oxidase,Dihydro Orotate Oxidase,Oxidase, Dihydro-Orotate,Oxidase, Dihydroorotate
D004583 Electrons Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called CATHODE RAYS. Fast Electrons,Negatrons,Positrons,Electron,Electron, Fast,Electrons, Fast,Fast Electron,Negatron,Positron
D005609 Free Radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Free Radical
D012996 Solutions The homogeneous mixtures formed by the mixing of a solid, liquid, or gaseous substance (solute) with a liquid (the solvent), from which the dissolved substances can be recovered by physical processes. (From Grant & Hackh's Chemical Dictionary, 5th ed) Solution
D014867 Water A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Hydrogen Oxide
D014965 X-Rays Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard X-rays are the higher energy, shorter wavelength X-rays. Soft x-rays or Grenz rays are less energetic and longer in wavelength. The short wavelength end of the X-ray spectrum overlaps the GAMMA RAYS wavelength range. The distinction between gamma rays and X-rays is based on their radiation source. Grenz Ray,Grenz Rays,Roentgen Ray,Roentgen Rays,X Ray,X-Ray,Xray,Radiation, X,X-Radiation,Xrays,Ray, Grenz,Ray, Roentgen,Ray, X,Rays, Grenz,Rays, Roentgen,Rays, X,X Radiation,X Rays,X-Radiations

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