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In a message dated 95-11-29 23:52:20 EST, you write: >The "free radical" theory has been around for decades and has never >been shown to be associated with *any* diseases. > > Dear Dr. Fink: The free radical theory has clearly been shown to be associated with the induction of somatic mutations in mitochondrial DNA (mtDNA) leading to impairment of the functional reserve of tissues heavily dependent on oxidative phosphorylation[OXPHOS] (brain, heart, muscle, etc.) . The end result has been a negative impact on progressive degenerative diseases of the brain (PD, Alzheimer's) and the most researched exemplary disorder, coronary artery heart disease. The chronic ischemia that results from reduction of myocardial blood flow due to a narrowing of the coronary artery lumen by plaque causes defective coupling of Complex I in the respiratory chain (by the way this is the complex most often found to be affected in PD patient platelets [not present in all cases] and in brain) which ultimately has a domino effect on the entire respiratory chain. The end result is increased free radical production leading to somatic mtDNA mutation accumulation and impaired function of tissues dependent on OXPHOS for energy. For a complete reference on this and a scheme for the paradigm for OXPHOS dysfunction and oxygen free radical damage see Chapter 46 "Oxidative Phosphorylation Diseases" by J Shoffner and D Wallace, The Metabolic & Molecular Basis of Inherited Disease" ed. Scriver C et al. 1995 edition (I think it's the 7th ed.) most particularily see the section of Chapt. 46 entitled "Somatic mtDNA Mutations and Aging" pp.1547-1550 and "Somatic mtDNA Mutations and Degenerative Diseases" pp.1551-1552. This book is the Bible for those of us in Medical Genetics and should be available in any Medical Genetics Dept. or in your medical school library. Delana Vaughan