Schoenfeld 2004 Toxicol Mech Methods: Difference between revisions
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|authors=Schoenfeld P | |authors=Schoenfeld P | ||
|year=2004 | |year=2004 | ||
|journal= | |journal=Toxicol Mech Methods | ||
|abstract=Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), a degradation product of chlorophyll formed in the intestinal tracts of ruminants, is a constituent of milk products and meat. Because it is a branched-chain fatty acid, degradation of phytanic acid is initiated in mammalian peroxisomes. In certain peroxisomal disorders such as in Refsum disease, phytanic acid accumulates dramatically throughout the body to levels that are believed to be associated with neurological and cardiac abnormalities. Here it is shown that nonesterified phytanic acid alters the permeability of the inner mitochondrial membrane by (1) increasing the conductance to hydrogen H<sup>+</sup>; (2) promoting opening of the permeability transition pore; and (3) initiating the release of endogenous Mg<sup>2+</sup>. But contrary to nonesterified long-chain fatty acids, phytanic acid only slightly stimulates the conductance of the inner membrane to K<sup>+</sup> and Cl<sup>-</sup>. These results suggest that pathologically high tissue levels of nonesterified phytanic acid increase the permeability of the inner membrane by ions through activities that are harmful for the synthesis of mitochondrial adenosine 5'-triphosphate as well as for mitochondrial integrity. | |abstract=Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), a degradation product of chlorophyll formed in the intestinal tracts of ruminants, is a constituent of milk products and meat. Because it is a branched-chain fatty acid, degradation of phytanic acid is initiated in mammalian peroxisomes. In certain peroxisomal disorders such as in Refsum disease, phytanic acid accumulates dramatically throughout the body to levels that are believed to be associated with neurological and cardiac abnormalities. Here it is shown that nonesterified phytanic acid alters the permeability of the inner mitochondrial membrane by (1) increasing the conductance to hydrogen H<sup>+</sup>; (2) promoting opening of the permeability transition pore; and (3) initiating the release of endogenous Mg<sup>2+</sup>. But contrary to nonesterified long-chain fatty acids, phytanic acid only slightly stimulates the conductance of the inner membrane to K<sup>+</sup> and Cl<sup>-</sup>. These results suggest that pathologically high tissue levels of nonesterified phytanic acid increase the permeability of the inner membrane by ions through activities that are harmful for the synthesis of mitochondrial adenosine 5'-triphosphate as well as for mitochondrial integrity. | ||
|keywords=Mg<sup>2+</sup>, Mitochondria, Permeability Transition, Phytanic Acid, Refsum Disease, Uncoupling | |keywords=Mg<sup>2+</sup>, Mitochondria, Permeability Transition, Phytanic Acid, Refsum Disease, Uncoupling |
Revision as of 17:52, 13 March 2013
SchΓΆnfeld P (2004) Phytanic acid toxicity: Implications for the permeability of the inner mitochondrial membrane to ions. Toxicol Mech Methods 14: 47-52. |
Schoenfeld P (2004) Toxicol Mech Methods
Abstract: Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), a degradation product of chlorophyll formed in the intestinal tracts of ruminants, is a constituent of milk products and meat. Because it is a branched-chain fatty acid, degradation of phytanic acid is initiated in mammalian peroxisomes. In certain peroxisomal disorders such as in Refsum disease, phytanic acid accumulates dramatically throughout the body to levels that are believed to be associated with neurological and cardiac abnormalities. Here it is shown that nonesterified phytanic acid alters the permeability of the inner mitochondrial membrane by (1) increasing the conductance to hydrogen H+; (2) promoting opening of the permeability transition pore; and (3) initiating the release of endogenous Mg2+. But contrary to nonesterified long-chain fatty acids, phytanic acid only slightly stimulates the conductance of the inner membrane to K+ and Cl-. These results suggest that pathologically high tissue levels of nonesterified phytanic acid increase the permeability of the inner membrane by ions through activities that are harmful for the synthesis of mitochondrial adenosine 5'-triphosphate as well as for mitochondrial integrity. β’ Keywords: Mg2+, Mitochondria, Permeability Transition, Phytanic Acid, Refsum Disease, Uncoupling
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Organism: Mammals"Mammals" is not in the list (Human, Pig, Mouse, Rat, Guinea pig, Bovines, Horse, Dog, Rabbit, Cat, ...) of allowed values for the "Mammal and model" property.
HRR: Oxygraph-2k
Pharmacology; Biotechnology