Dialdehyde reductase

A further remarkable finding in the hydrolysis of aflatoxin B1 exo-8,9-epoxide is the relative instability of the dihydrodiol, which under basic conditions exists in equilibrium with an aflatoxin dialdehyde, more precisely a furofuran-ring-opened oxy anionic a-hydroxy dialdehyde (10.134, Fig. 10.30). The dihydrodiol is the predominant or exclusive species at pH < 7, whereas this is true for the dialdehyde at pH >9, the pK value of the equilibrium being 8.2 [204], The dialdehyde is known to form Schiff bases with primary amino groups leading to protein adducts. However, the slow rate of dialdehyde formation at physiological pH and its reduction by rat and human aldo-keto reductases cast doubts on the toxicological relevance of this pathway [206]. 

Recently, de novo-synthesized four-helix polypeptides were applied to mimic functions of cytochrome b and to tailor layered cross-linked electrocatalytic electrodes. A four-helix bundle de novo protein (14728 Da) that includes four histidine units in the respective A -helices was assembled on Au electrodes (Figure 22A). Two units of Fe(III)-protoporphyrin IX were reconstituted into the assembly to yield a vectorial electron-transfer cascade [157]. The de novo-synthesized protein assembly forms affinity complexes with the cytochrome-dependent nitrate reductase (NR) and with Co(II) protoporphyrin IX-reconstituted myoglobin [158]. The resulting layered complex of Fe(III) de novo protein-NR or Fe(lll)-de novo protein-Co(II)-reconstituted myoglobin was cross-linked with glutaric dialdehyde to yield electrically contacted electrocatalytic electrodes. The Fe(lll)-de novo protein-NR electrode assembly was applied for the electrocatalyzed reduction NO3 to NOt" and acted as an amperometric sensor (Figure 22B). The Fe(III)-de novo... 

Microperoxidase-11, MP-11, is a heme-undecapeptide that is prepared by the digestion of cytochrome c and it includes the active surrounding of cytochrome MP-11 was immobilized on electrode surface s and its electrochemistry was characterized. The MP-11-modified electrodes were reported to act as effective electron mediator interfaces for the reduction of cytochrome c, hemoglobin, myoglobin and nitrate reductase (cytochrome c-dependent). The MP-11-mediated activation of nitrate reductase, NR, was employed to assemble an integrated MP-11/NR electrode for the bioelectrocatalyzed reduction of nitrate (NO3 ) to nitrite (NO2). An affinity complex between a MP-11-functionalized electrode and NR (/Q = 3.7x10 M ) was crosslinked with glutaric dialdehyde to yield the electrically contacted electrode for the bioelectrocatalyzed reduction of nitrate to nitrite. In this system the reduced MP-11 mediates ET to NR and activates the enzyme towards the reduction of NO3. 

Periodate-oxidized NADP has been used as an affinity label for other NADP-specific enzymes including pigeon liver malic enzyme (72, 73), spinach ferre-doxin-NADP reductase (74, 75), and Leuconostoc mesenteroides glucose-6-phosphate dehydrogenase (76). Recently, a new fluorescent dialdehyde derivative has been reported as an affinity label of NADP sites, namely, periodate-oxidized 3-aminopyridine adenine dinucleotide phosphate (77). 

Guengerich FP, Cai H, McMahon M, Hayes JD, Sutter TR, Groopman JD, Deng Z, Harris TM. Reduction of aflatoxin B1 dialdehyde by rat and human aldo-keto reductases. Chem Res Toxicol 2001 14 727-737. 

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