Oxidation-phosphorylation defects

Citrin is an aspartate-glutamate antiporter that has a role both in the urea cycle and in the malate aspartate shuttle. It is necessary for the transport of aspartate produced in the mitochondria into the cytosol, where it is used by AS. Its role in the malate-aspartate shuttle is to transport cytosolic NADH reducing equivalents into the mitochondria, where they are used in oxidative phosphorylation. Defects in citrin cause citrullinemia type II. Patients manifest later-onset intermittent hyperammonemic encephalopathy as in HHH syndrome. 

Gu M, Cooper JM, Butler P, Walker AP, Mistey PK, Dooley JS and SchapieaAHV (2000) Oxidative-phosphorylation defects in liver of patients with Wilson s disease. Lancet 356 469-474. 

Gu M, Cooper JM, Butler P, Walker AP, Mistry PK, Dooley JS, Schapira AH. Oxidative-phosphorylation defects in Uver of patients with Wilson s disease. Lancet 2000 356 469-474 Hamza I, Schaefer M, Klomp LW, Githn JD. Interaction of the copper chaperone HAHl with the Wilson disease protein is essential for copper homeostasis. Proc Natl Acad Sci USA 1999 96 13363... 

Ischaemic hearts of 7 patients aged 48 to 63 years had increased mtDNA damage and OXPHOS gene expression, suggesting that mtDNA damage is associated with OXPHOS deficiency (Corral-Debrinski et al. 1991). Oxidative phosphorylation defects may also play a role in some other forms of cardiac disease as idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, myocarditis, brown atrophy and coronary aAerosclerosis. 

Vanlander AV, Jorens PG, Smet J, De Paepe B, Verbrugghe W, Van den Eynden GG, et al. Inborn oxidative phosphorylation defect as risk factor for propofol infusion syndrome. Acta Anaesthesiol Scand 2012 56 520-5. 

Bithionol interferes with the neuromuscular physiology of helminths, impairs egg formation, and may cause defects in the protective cuticle covering the worm. At the biochemical level, the oxidative phosphorylation of the worm is inhibited. 

The biochemical classification of mitochondrial DNA is based on the five major steps of mitochondrial metabolism. These steps are illustrated in Figure 42-3 and divide mitochondrial diseases into five groups defects of mitochondrial transport, defects of substrate utilization, defects of the Krebs cycle, defects of the respiratory chain and defects of oxidation-phosphorylation coupling. 

Peterson et al. found an increase in intramyocellular lipid content and reduction in mitochondria phosphorylation (mitochondrial rates of ATP production) in insulin-resistant subjects versus insulin-sensitive subjects. They concluded that their results supported the h) othesis that insulin resistance is due to dysregulation of intramyocellular fatty acid metabolism, which maybe caused by an inherited defect in mitochondrial oxidative phosphorylation. 

Fosslien E. Review mitochondrial medicine-molecular pathology of defective oxidative phosphorylation. Ann Clin Lab Sci 2001 31 25-67. 

A mutation in any of the 13 protein subunits, the 22 tRNAs, or the two rRNAs whose genes are carried in mitochondrial DNA may possibly cause disease. The 13 protein subunits are all involved in electron transport or oxidative phosphorylation. The syndromes resulting from mutations in mtDNA frequently affect oxidative phosphorylation (OXPHOS) causing what are often called "OXPHOS diseases."3-6 Mitochondrial oxidative phosphorylation also depends upon 100 proteins encoded in the nucleus. Therefore, OXPHOS diseases may result from defects in either mitochondrial or nuclear genes. The former are distinguished by the fact that they are inherited almost exclusively maternally. Most mitochondrial diseases are rare. However, mtDNA is subject to rapid mutation, and it is possible that accumulating mutants in mtDNA may be an important component of aging.h k... 

Brini, M., Pinton, P., King, M. P., Davidson, M., Schon, E. A., and Rizzuto, R., 1999, A calcium signaling defect in the pathogenesis of a mitochondrial DNA inherited oxidative phosphorylation... 

G5703A tRNAAsn Severe defects in oxidative phosphorylation HI... 

High Blood Alanine Level Associated with Defects in Oxidative Phosphorylation Most individuals with genetic defects in oxidative phosphorylation are found to have relatively high concentrations of alanine in their blood. Explain this in biochemical terms. 

Luft et al50 reported a case of severe hypermetabolism of non-thyroid origin and a defect in the maintenance of mitochondrial respiratory control. DiMauro et al51 isolated mitochondrial fractions from such a patient and studies of oxidative phosphorylation showed defective respiratory control and normal phosphorylation capacity (loose coupling). The rate of energy-dependent calcium uptake by isolated mitochondria was normal, but the amount of calcium accumulated was much decreased. Calcium could not be retained and was spontaneously released into the medium within 30 seconds. "Recycling" of calcium between mitochondria and cytosol may take place in vivo and result in sustained stimulation of respiration and loose coup-... 

A slowly progressive congenital neuromuscular disorder was reported in which the respiratory chain-linked energy transfer at a level common to all three energy coupling sites of respiratory chain was defective.52 Uncouplers of mitochondrial oxidative phosphorylation (2,4-dinitrophenol and carbonylcyanide-m-chlorophenylhydrazone) (5) produced mitochondrial myopathy in rats.53... 

J2. Jacobson, B. E., Blanchaer, M. C., and Wrogemann, K., Defective respiration and oxidative phosphorylation in muscle mitochondria of hamsters in the late stages of hereditary muscular dystrophy. Can. J. Biochem. 48, 1037-1042 (1970), J3. Jenkins, K. J., Ketone body metabolism in nutritional myopathy. Can. J. Biochem. 42, 1153-1160 (1964). 

FIGURE 10-36 Cytoplasmic inheritance of the petite mutation in yeast. Petite-strain mitochondria are defective in oxidative phosphorylation owing to a deletion in mtDNA. 

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