Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In contrast to its lethargy at physiological pH, horse heart cytochrome c can be oxidized at room temperature by the axial inner sphere oxidant bromomalononitrile (BMN) at higher acidities. The following stoichiometry obtains: 2Fe11 c + BrCH(CN2) + H+ leads to 2FeIII c + CH2(CN)2 + Br-, and the rate law is given by: rate = k2(FeIIc)(BMN). At an ionic strength of 1.0 (KCl), second-order rate constants vary from 300 l. per mol per sec (pH 2-3) to 0(pH 9). Below pH 6 there is a noticeable increase in rate with ionic strength while there is no specific salt effect for the process. At pH 7.4 there is no influence of added salt (0.01-1.0 M) upon the slow rate of reaction. The vast changes in rate occur over a pH region (3-6) in which only very minor changes in the visible spectrum of the cytochrome are manifest. The results are interpreted in terms of a conformational isomerism of cytochrome c in which the effective redox geometry alters from a predominantly "short C" form (in which an axial position is available for substitution) at lower pH's to a predominantly "C" form (axial positions encumbered) in the physiological region. At 5 degrees, pH 7.4, both hemes of beef heart cytochrome oxidase are oxidized by the addition of BMN (k2 = 29 plus or minus 3 l. per mol per sec). However, the reaction is inhibited by potassium cyanide and the protein containing iron(II) cyt alpha along with the cyano adduct of iron(II) or iron(III) cyt alpha3 is inert. The results demonstrate cytochrome alpha3 as the site of reaction and that alpha reduces alpha3 in the process. Cytochrome oxidase does catalyze the oxidation of cytochrome c with BMN as substrate. Taken together the results provide additional support for a recent theory and they demonstrate BMN to be an efficient probe for the effective redox geometry of a hemoprotein in solution.
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PMID:Conformational isomerism and effective redox geometry in the oxidation of heme proteins by alkyl halides, cytochrome c, and cytochrome oxidase. 23 44

A 3-day-old girl had a syndrome of lethargy and lactic acidosis. Pregnancy and delivery had been normal; there was no consanguinity or family history of neuromuscular disease. At age 4 1/2 months, she had generalized weakness, hypotonia, areflexia, and macroglossia. She developed cyanosis and respiratory failure, and marked cardiomegaly was noted. She died at age 8 1/2 months of cardiac arrest. Results from a muscle biopsy specimen obtained at age 4 1/2 months showed ragged-red fibers and increased glycogen and lipid droplets. With the cytochrome c oxidase reaction, only 5% of the fibers stained positively in the biopsy specimen. Cytochrome c oxidase activity was 7.3% of normal in muscle mitochondria and 12.2% of normal in heart mitochondria. Reduced-minus-oxidized cytochrome spectra showed lack of the cytochrome aa3 peak. Immunotitration using antibodies against purified human heart cytochrome c oxidase showed normal amount of cross-reacting material in both heart and muscle. The genetic error could have involved a cytochrome c oxidase isozyme common to heart and muscle.
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PMID:Myopathy and fatal cardiopathy due to cytochrome c oxidase deficiency. 302 95

The paroxysmal dyskinesias are a group of neurological disorders described by intermittent attacks of involuntary abnormal movements superimposed on a relatively normal baseline. The neuroanatomical substrates for these attacks are not fully understood, though available evidence from studies of affected people and animal models points to dysfunction in the basal ganglia or cerebellum. In the current studies, the anatomical basis for paroxysmal dyskinesias in lethargic mice was determined via histochemical methods sensitive to changes in regional brain activity followed by surgical elimination of the suspected source. Cytochrome oxidase histochemistry revealed increased activity in the red nucleus. Surgical removal of the cerebellum worsened ataxia but eliminated paroxysmal dyskinesias. These studies support the hypothesis that abnormal cerebellar output contributes to paroxysmal dyskinesias.
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PMID:Neuroanatomical substrates for paroxysmal dyskinesia in lethargic mice. 1756 8