Electron transferring flavoprotein deficiency

Table 3.2.5 Disorders detectable by the in vitro probe assay. ETF Electron transfer flavoprotein, MADD multiple acyl-CoA dehydrogenase deficiency...

Figure 17.4 The electron transport chain of mitochondria. Triangles indicate sites of inhibition by various compounds. Cyt, cytochrome ETF, electron transfer flavoprotein. (Reproduced with permission from Moreadith RW, Batshaw ML, Ohnishi T, Kerr D, Knox B, Jackson D, Hruben R, Olson J, Reynafarje B, Lehninger AL. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis J Clin Invest 74 685-697, 1984.)...

Goodman, S.I., McCabe, E.R.B., Fennessey, P.V. and Mace, J.W. (1980), Multiple acyl-CoA dehydrogenase deficiency (Glutaric aciduria type II) with transient hypersarcosinemia and sarcosinuria Possible inherited deficiency of an electron transfer flavoprotein. Pediatr. Res., 14,12. 

Flavodoxins. Flavodoxins are small, 36 kDa, flavoproteins containing one non-covalently bound FMN as cofactor. They are synthesized by cyanobacteria when the culture medium is iron deficient and replace ferredoxin in electron-transfer reactions including reduction of nitrogenase in Klebsiella and Azotobacter and electron transfer from photosynthetic membranes to fer-redoxin-NADP+ reductase. 

The system depends on an electron transport pathway that transfers electrons from NADPH through a flavoprotein (NADPH cytochrome P-450 reductase) to cytochrome P-450 that is the terminal oxidase of the chain (10). The xenobiotic first forms a complex with the oxidized form o cytochrome P-450 which is reduced by an electron passing down the chain from NADPH. The reduced cytochrome P-450/substrate complex then reacts with and activates molecular oxygen to an electrophilic oxene species (an electron deficient species similar to singlet oxygen) that is transferred to the substrate with the concommitant formation of water. Cytochrome P-450 thus acts primarily as an oxene transferase (2). Substrate binding is a relatively nonspecific, passive process that serves to bring the xenobiotic into close association with the active center and provide the opportunity for the oxene transfer to occur. 

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