Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with mevalonate kinase deficiency suffer from psychomotor retardation, ataxia with progredient cerebellar atrophy, and myopathy. The pathophysiology of the disease remains unclear. The mevalonate kinase product, cholesterol, is within the normal range in patient plasma and fibroblasts. In search of the pathophysiology of this disorder, another mevalonate kinase product, ubiquinone-10, was studied. The concentrations of ubiquinone-10 in patient plasma (n = 6) and ubiquinol-10 in patient LDL (n = 2) and the synthesis of ubiquinone-10 in patient fibroblasts (n = 4) were determined. After oxidative modification of LDL by copper in vitro, the concentrations of alpha-tocopherol and polyunsaturated fatty acids in LDL and the relative electrophoretic mobility of LDL were measured to determine the antioxidant capacity of LDL samples of two affected siblings. The ubiquinone-10 concentrations in plasma samples (median = 508 micrograms/L, range = 488-642 micrograms/L) versus controls (median = 613 micrograms/L, range = 564-809 micrograms/L; p < 0.005) were decreased. In LDL samples of two affected siblings, the concentration of ubiquinol-10 and the resistance to oxidation in vitro were found decreased during intercurrent patient crisis condition. In patient fibroblasts (median = 533 dpm/mg protein, range = 399-1,047 dpm/mg protein) versus controls (median = 40,731 dpm/mg protein, range = 12,774-54,739 dpm/mg protein), the synthesis of ubiquinone was found to be decreased. We conclude that mevalonate kinase deficiency leads to a decreased synthesis of ubiquinone-10 and that ubiquinone-10 deficiency is responsible for the clinical progression of this disease characterized by increased lipid peroxidation, cerebellar atrophy, cataract development, and myopathy with increased creatine kinase activity.
 ...
PMID:Decreased plasma ubiquinone-10 concentration in patients with mevalonate kinase deficiency. 823 12

Reactive oxygen species (ROS) generated in the presence of O(2) by mitochondria, phagocytic cells, peroxisomes, and cytochrome P450 enzymes under physiological conditions, may play a dual function in the human organism. On the one hand, they participate in cell signal transduction cascades, leading to the activation of some transcription factors responsible for regulating of the expression of genes relevant for cell growth and differentiation. On the other hand, they cause oxidative damage of cellular DNA, protein and lipids, resulting in the initiation or development of numerous diseases such as cancer, cardiovascular diseases, type 2 diabetes mellitus, cataract, rheumatoid arthritis, or different neurodegenerative diseases. Both endogenous compounds (glutathione, ubiquinol, urate, bilirubin) and enzymes (superoxide dismutase, catalase, glutathione peroxidase) are engaged in the detoxification of ROS. In addition, numerous dietary components such as vitamin C, vitamin E, carotenoids, and polyphenols are thought to be involved in the antioxidant defense system. The present review article is focused on the summary and the assessment of research on the impact of dietary antioxidants in the prevention of chronic diseases, particularly cancer and cardiovascular diseases.
 ...
PMID:A review of natural and synthetic antioxidants important for health and longevity. 2066 18