A function for α-tocopherol: Stabilization of the microsomal membrane from radical attack during TPNH-dependent oxidations |
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Authors: | Paul B McCay J Lee Poyer Peter M Pfeifer Hubert E May James M Gilliam |
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Affiliation: | (1) Oklahoma Medical Research Foundation, University of Oklahoma School of Medicine, 73104 Oklahoma City, Oklahoma;(2) Department of Biochemistry and Molecular Biology, University of Oklahoma School of Medicine, 73104 Oklahoma City, Oklahoma;(3) Present address: Department of Chemistry, Oral Roberts University, 74105 Tulsa, Okla.;(4) Present address: Department of Biophysics, Yale University, 06520 New Haven, Conn. |
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Abstract: | Events accompanying electron transport in the membrane fraction of liver and other tissues have led us to propose a specific
function for α-tocopherol based on a sequence of biochemical changes we observed to occur in these membranes and on pertinent
information from other laboratories. The activity of a membrane-bound enzyme system (TPNH oxidase) which involves transport
of electrons from substrate to oxygen, has been shown to promote simultaneous formation of peroxide functions on the β position
polyunsaturated fatty acids (PUFA) of phospholipids in the membrane. The phospholipid peroxides then undergo a chain cleavage
reaction producing phospholipids containing a variety of carbonyl moieties in the β position. The process results in marked
alteration of the membrane structure. During the overall reaction α-tocopherol present in the membrane is converted to a compound
more polar than tocopheryl quinone and the conversion is dependent on the same enzymic factors promoting the phospholipid
alterations. The membrane alteration process is enhanced in microsomes from animals fed diets containing relatively high levels
of PUFA or diets low in α-tocopherol, and is diminished by low levels of dietary PUFA or relatively high levels of α-tocopherol.
The experimental data indicate that enzymic electron transport associated with TPNH oxidation by the microsomal membrane involves
free radical functions. The latter apparently can promote extensive peroxidative alterations of phospholipids that result
in structural changes in the membrane unless adequate α-tocopherol is present in this organelle. This system appears to be
part of the microsomal drug metabolizing system. |
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