Mechanism biological hydroxylation

G.S. Boyd u. R.M.S. Smellic, Biological Hydroxylation Mechanisms, Academic Press, London New York... 

PROBABLE FATE photolysis, no direct photolysis, indirect photolysis is too slow to be important, the vapor is expected to react with photochemically produced hydroxyl radicals, with an estimated half-life of 22.2 hrs oxidation not an important process, photooxidation half-life in water 2.4-12.2 yrs, photooxidation half-life in air 21 hrs-8.8 days hydrolysis expected to be too slow to be important under natural conditions, first-order hydrolytic half-life 8.8 yrs volatilization not considered as important as sorption, however, there is very little data, volatilizes from dry soil surfaces, volatilization may be important in shallow rivers sorption adsorption onto solids and particles and complexation with humic material (flilvic acid) are the principal transport mechanisms biological processes bioaccumulation, biodegradation, and biotransformation by many organisms (including humans) are very significant fates... 

PROBABLE FATE photolysis-, photochemical reactions in aqueous media are probably unimportant, slow decomposition in the troposphere in the presence of nitrogen oxides is possible, appreciable photodissociation may occur in stratosphere, photooxidation half-life in air 19.1-191 days oxidation-, probably unimportant, in troposphere, oxidation by hydroxyl radicals to CO2, CO, and phosgene is important fate mechanism hydrolysis not an important fate process, first-order hydrolytic half-life 704 yrs volatilization due to high vapor pressure, volatilization to the atmosphere is rapid and is a major transport process sorption sorption to inorganic and organic materials is not expected to be an important fate mechanism biological processes bioaccumulation is not expected, biodegradation may be possible but very slow compared with evaporation... 

Shaik, S., Ogliaro, R, de Visser, S. R, Schwarz, H., 8c Schroeder, D. (2002). Two state reactivity mechanism of hydroxylation and epoxidation by cytochrome P450 revealed by theory. Current Opinion in Chemical Biology, 6, 556. 

Biological Hydroxylation Mechanisms, Biochemical Society Symposium No. 34, ed. G. S. Boyd and R. M. S. Smellie. Academic Press, London and New York, 1972. 

Although it is being found that vitamin D metaboUtes play a role ia many different biological functions, metaboHsm primarily occurs to maintain the calcium homeostasis of the body. When calcium semm levels fall below the normal range, 1 a,25-dihydroxy-vitainin is made when calcium levels are at or above this level, 24,25-dihydroxycholecalciferol is made, and 1 a-hydroxylase activity is discontiaued. The calcium homeostasis mechanism iavolves a hypocalcemic stimulus, which iaduces the secretion of parathyroid hormone. This causes phosphate diuresis ia the kidney, which stimulates the 1 a-hydroxylase activity and causes the hydroxylation of 25-hydroxy-vitamin D to 1 a,25-dihydroxycholecalciferol. Parathyroid hormone and 1,25-dihydroxycholecalciferol act at the bone site cooperatively to stimulate calcium mobilization from the bone (see Hormones). Calcium blood levels are also iafluenced by the effects of the metaboUte on intestinal absorption and renal resorption. 

The hydroxyl radical plays two essentially different roles (a) as a reactant mediating the transformations of xenobiotics and (b) as a toxicant that damages DNA. They are important in a number of environments (1) in aquatic systems under irradiation, (2) in the troposphere, which is discussed later, and (3) in biological systems in the context of superoxide dismutase and the role of iron. Hydroxyl radicals in aqueous media can be generated by several mechanisms ... 

O Connell, M.J., Halliwell, B., Moothouse, C.P., Aruoma, O.I., Baum, H. and Peters, T.J. (1986). Formation of hydroxyl radicals in the presence of ferritin and haemosiderin. Is haemosiderin formation a biological protective mechanism Biochem. J. 234, 727-731. 

He, X. and Ortiz de Montellano, P.R. (2004) Radical rebound mechanism in cytochrome P-450 catalyzed hydroxylation of multifaceted radical clocks a-and p-thujone. The Journal of Biological Chemistry, 279, 39479-39484. 

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