Disease relevance of Fdxr

• However, the mechanisms by which ischemia regulates AR activity remain unclear [1].
• The conversion of glucose to sorbitol by aldose reductase (AR) and its subsequent intracellular accumulation have been implicated in the pathogenesis of diabetic cataracts [2].
• The reconstituted system containing the membrane fraction prepared from recombinant E. coli cells, adrenodoxin and adrenodoxin reductase was examined for the metabolism of 25(OH)D3, 1alpha,25(OH)2D3 and their related compounds [3].
• The activation of the polyol pathway through aldose reductase (AR) might be involved in diabetic neuropathy [4].
• The rat nNOS heme domain was linked with either cytochrome P450 reductase, adrenodoxin reductase, or the reductase domain from Bacillus megaterium cytochrome P450, BM-3 [5].

High impact information on Fdxr

• The mitochondrial P450 system electron transport proteins, adrenodoxin and adrenodoxin reductase, are also induced but adrenodoxin shows a faster induction [6].
• Aldose reductase (AR) reduces cytotoxic aldehydes and glutathione conjugates of aldehydes derived from lipid peroxidation [1].
• These data indicate that reactive oxygen species formed in the ischemic heart activate AR by modifying its cysteine residues to sulfenic acids [1].
• A different conformational state of the mitochondrial targeted cytochrome P450 2E1 (P450 MT5) is likely to be responsible for its observed preference for adrenodoxin and adrenodoxin reductase electron transfer proteins [7].
• The purified P450MT2 showed a preference for adrenodoxin + adrenodoxin reductase electron donor system and exhibited high erythromycin N-demethylation activity [8].

Chemical compound and disease context of Fdxr

• Sorbinil (CP 45,634), a potent aldose reductase (AR) inhibitor, has the ability to normalize both sorbitol levels and functional parameters such as orthograde axonal transport and motor nerve conduction velocity in peripheral nerves of diabetic rats, which implicates flux through the polyol pathway in the pathophysiology of diabetic neuropathy [9].

Biological context of Fdxr

• The activity, however, was restored to preparations from both PB-induced and 3-MC-induced mitochondrial enzymes (AFB1 activation, ethylmorphine, and benzphetamine deamination and BaP metabolism) by addition of purified rat liver cytochrome P-450 reductase, and beef adrenodoxin and adrenodoxin reductase [10].
• A new working hypothesis that there is a hitherto unrecognized binding site on the aldose reductase (AR) enzyme with strong affinity for benzothiazoles was pursued for the design of novel, potent aldose reductase inhibitors (ARIs) [11].
• Although aldose reductase (AR) is a critical participant in osmoregulation, and the metabolism of glucose and aldehydes derived from lipid peroxidation, post-translational mechanisms regulating its activity have not been identified [12].
• Ferredoxin reductase levels in the ovaries of pigs and superovulated rats during follicular cell growth and luteinization [13].
• The preservation of the action potential was reversed by the administration of insulin, but not by treatment with an aldose reductase (AR) inhibitor [14].

Anatomical context of Fdxr

• Galactose intoxication of rats was used to disrupt metabolism of Schwann cells and skeletal muscle, two sites that contain the polyol-forming enzyme aldose reductase (AR) [15].
• This occurs as a direct result of the enhanced expression of SCP2, P450scc, adrenodoxin and adrenodoxin reductase, proteins specifically required to transport and process cholesterol for steroid production in the large luteal cell [16].
• The concentration of ferredoxin reductase in porcine granulosa cells doubled during growth of follicles from small (1-2 mm diameter) to large (6-12 mm diameter) [13].
• The increase in ferredoxin reductase during follicular development and luteinization, therefore, correlates well with the increase in mitochondria in the cells, but does not correlate with the dramatic increase in cholesterol side-chain cleavage activity which occurs during luteinization [13].
• The induction of aldose reductase (AR) mRNA expression and its activity by glucose were investigated in fetal rat aortic smooth muscle (A10) cells [17].

Associations of Fdxr with chemical compounds

• Cholesterol 27-hydroxylase activity of the ER-associated 1-44/1A1-CYP27 fusion protein can be reconstituted with cytochrome P450 reductase, but the mitochondrial associated fusion protein is functional with adrenodoxin + adrenodoxin reductase [18].
• It is not clear whether sorbitol accumulation results from increases in substrate, activity of the aldose reductase (AR) protein molecule, or activity due to an increase in the amount of enzyme present [19].
• Sorbinil, an aldose reductase (AR) inhibitor, attenuated GS-DHN levels and cyanamide, an aldehyde dehydrogenase inhibitor, decreased formation of HNA [20].
• Treatment of the galactosemic rats with sorbinil, an aldose reductase (AR) inhibitor, was found to block galactitol formation and protect against the loss of MI, taurine, and other amino acids [21].
• The three nitroaromatic compounds are reduced by L-lactate cytochrome c-reductase, adrenodoxin reductase, and NADPH:cytochrome P-450 reductase (EC 1.6.2.4), the efficiencies of the enzymatic reductions being roughly related to the reduction potentials of these pseudo-substrates [22].

Other interactions of Fdxr

• In vitro reconstitution experiments show that P-450mt4 can metabolize a wide range of substrates such as benzphetamine, (dimethylamino)antipyrine, aflatoxin B1, and vitamin D3, exclusively in the presence of mitochondrial-specific ferredoxin and ferredoxin reductase as electron carriers [23].
• Rat adrenal mitochondria contain approximately equal levels of P450scc and P45011 beta, each reduced by NADPH through adrenodoxin reductase (ADX-reductase) and adrenodoxin (ADX) [24].

Analytical, diagnostic and therapeutic context of Fdxr

• The AR activity was not further enhanced by reperfusion [1].

References