Phosphorylation disease

Shoffner JM, Wallace DC (1995) Oxidative phosphorylation diseases. In Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein (eds) The Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, New York pp 1535-1609... 

Shoffner, J. M., Maternal inheritance and the evaluation of oxidative phosphorylation diseases. Lancet 348, 1283-1288 (1996). 

Shoffner JM, Wallace DC Oxidative phosphorylation diseases and mitochondrial DNA mutations diagnosis and treatment. Annu Rev Nutr 14 535-568,1994. 

Esterification of the corresponding quinoline-4-carboxylic acid gave the ester 511 which upon reaction with pyrrolidine in THE gave the amide 512. Its phosphorylation and reaction with 513 in presence of KOBu afforded 514 which is useful in the treatment of anxiety, sleep disorders, panic states, convulsions, muscle disorders (95WOP9514020) and chronic neurodegen-erative diseases (97WOP9700074) (Scheme 87). 

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

Papasozomenos, S.C. Su, Y. (1991). Altered phosphorylation of tau protein in heat shocked rats and patients with Alzheimer s disease. Proc. Natl. Acad. Sci. USA 88,4543-4547. 

Hibbs ML, Tarlinton DM. Armes J. Grail D. Hodgson G, Maghtto R, Stacker SA, Dunn AR Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease. Cell 1995 83 301-311. Nishizumi H, Yamamoto T Impaired tyrosine phosphorylation and Ca + mobiUzation, but not degranulation, in Lyn-deficient bone marrow-derived mast cells. J Immunol 1997 158 2350-2355. 

Creatine phosphate is formed from ATP and creatine (Figure 49-16) at times when the muscle is relaxed and demands for ATP are not so great. The enzyme catalyzing the phosphorylation of creatine is creatine kinase (CK), a muscle-specific enzyme with clinical utility in the detection of acute or chronic diseases of muscle. 

The inhibition of the phosphorylation of IkBoc by celastrol in the NF-kB signaling pathway is not cell specific72-75 and thus significantly broadened the potential medicinal applications of natural triterpene QMs. Celastrol 76 has been evaluated in the treatment of Crohn s disease,76 which is a chronic relapsing inflammatory bowel disease. In the peripheral blood mononuclear cells, celastrol 76 reduced the levels of... 

Gleevec ) is a tyrosine kinase inhibitor used as first-line therapy in the majority of patients with CML. As a potent tyrosine kinase inhibitor, imatinib inhibits phosphorylation of various proteins involved in cell proliferation. Imatinib works by binding to the ATP-binding pocket of BCR-ABL.7 The drug induces complete hematologic responses in more than 95% of patients and complete cytogenetic responses in about 80% of patients in chronic phase.8 Most patients have traces of the disease when measured by RT-PCR and are not cured of their disease. 

Hunter, T., The Croonian Lecture 1997. The phosphorylation of proteins on tyrosine its role in cell growth and disease, Philos. Trans. Roy. Soc. London B (Biol. Sci.), 353, 583-605, 1998. 

The answer is d. (Katzung, pp 831-832.) Zidovudine competitively inhibits HIV-1 nucleoside reverse transcriptase. It is also incorporated in the growing viral DNA chain to cause termination. Each action requires activation via phosphorylation of cellular enzymes. Zidovudine decreases the rate of clinical disease progression and prolongs survival in HIV-infected patients. 

Abnormal phosphorylation of specific neural proteins may contribute to the development of Alzheimer s disease 410... 

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