[9] Stereospecificities of the pyridine nucleotide-linked enzymes

You, Kwan-sa

doi:10.1016/s0076-6879(82)87011-0

Cited by 42 publications

(15 citation statements)

References 125 publications

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“…8, E1 to E3) have been found for the stereochemical course of the oxidation of NADH and reduction of a carbonyl group to an alcohol by different alcohol dehydrogenases, i.e., the (pro-R)-or (pro-S)-hydrogen of NADH is transferred to the Si or Re face of the carbonyl substrate. Dehydrogenases with these stereochemical preferences are well known (27,36,38,39). Figure 8 (E4) describes the reduction of NAD ϩ and oxidation of an alcohol formed by dihydrodiol dehydrogenases; i.e., the hydrogen transfer occurs from the Re face of the alcohol to the Si face of NAD, giving (4S)-NADH (1,32).…”

Section: Discussionmentioning

confidence: 99%

Stereochemical course of two arene-cis-diol dehydrogenases specifically induced in Pseudomonas putida

et al. 1997

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Catabolism of nonphenolic arenes is frequently initiated by dioxygenases, yielding single isomer products with two adjacent hydroxylated asymmetric centers. The next enzymic reaction dehydrogenates these cyclic cis-diols, with aromatization yielding catechols for ring cleavage. H was transferred from both the 2-and 3-C atoms of (2S,3R)-p-toluate-2,3-dihydrodiol with specifically deuterated species in approximately equal amounts; and (iii) the unexpected lack of stereo-and regioselectivity of p-toluate-2,3-diol dehydrogenase was supported by kinetic isotope effect studies.Most nonhydroxylated arenes biodegraded by bacteria are dihydroxylated initially, in NADH-dependent reactions, to give cis-1,2-diol cyclohexadiene intermediates (10,(12)(13)(14)17). The second reaction of these catabolic pathways is usually an NADdependent dehydrogenation with concomitant rearomatization of the ring to give a catechol. The seminal work of Gibson (11) established this central, and apparently sole, preserve of bacterial evolution; cis-1,2-diol formation in other biological kingdoms has not yet been described.These dihydroxylation and dehydrogenation systems pose several questions of enzyme stereospecificity. Two asymmetric centers are formed in a single initial reaction, and they are destroyed in the next catabolic reaction by dehydrogenation to catechols. There are therefore two possible stereochemical questions to address for each reaction, to describe the diastereochemistry of these enzymic reactions. (i) Which hydrogen of NADH (4R or 4S) is transferred for the dihydroxylation? (ii) Which atom in the diol product receives hydrogen (H ϩ or H Ϫ )? For the successive dehydrogenation reactions, the inverse questions require solution. (iii) To which face of the nicotinamide ring of NAD ϩ is hydride ion transferred? (iv) From which C center of the dihydrodiol is hydride transferred to give NADH. In this paper we provide answers to questions ii, iii, and iv.Previously we have shown that the flavoprotein hydroxylases for orcinol, resorcinol, and 3-hydroxybenzoate (4-and 6-hydroxylases) donate the (4S) proton from NADH, by 3 H and 2 H isotope experiments (30, 37). You et al. (38) confirmed these results by proton nuclear magnetic resonance (NMR) experiments with five enzymes that we provided. A recent study by Schläfli et al. (34), using the tritium method to discriminate the (4S) and (4R) protons in NADH, examined the stereospecificity of hydride (tritide) transfer by the flavin cytochrome reductases of several arene-cis-1,2-dihydroxylases. There appears to be a consistency, since the examined enzymes of class I, e.g., phthalate dioxygenase and 2-chlorobenzoate dioxygenase, used the (4S)-3

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Section: Discussionmentioning

confidence: 99%

Stereochemical course of two arene-cis-diol dehydrogenases specifically induced in Pseudomonas putida

et al. 1997

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“…In the cells, synthesized NAD 1 is reduced to NADH through the acceptance of an additional hydrogen (H) at the redox site (C-4 carbon of the pyridine ring), whereas the removal of either of the two H atoms at the redox site of NADH reforms NAD 1 (9,10). The reversible transfer of H to and from either the pro-R or pro-S side at the redox site of NAD 1 /NADH is catalyzed by oxidoreductases exhibiting the opposite stereospecificity for the coenzymes (9,10 …”

Section: Nadmentioning

confidence: 99%

“…The reversible transfer of H to and from either the pro-R or pro-S side at the redox site of NAD 1 /NADH is catalyzed by oxidoreductases exhibiting the opposite stereospecificity for the coenzymes (9,10 …”

Section: Nadmentioning

confidence: 99%

Formation of [Nicotinamide-2H3]NAD+ from [2H4]Nicotinamide and [2H4]Nicotinic Acid in Human HepG2N Cells and Involvement of 2H/1H Exchange at the Redox Site of NAD+/NADH

Hara

Shibata

Osago

et al. 2014

J Nutr Sci Vitaminol

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NAD1 plays critical roles in various biological processes, such as metabolism of carbohydrates (1) and fat (2), the circadian cycle (3,4), and aging (5, 6) through the function of SIRT1. Cellular NAD 1 concentration, which is regulated through the synthesis from nicotinamide (Nam) and nicotinic acid (NA) and breakdown to Nam (Fig. 1A) (7), would thus have a significant impact on mammal physiology, including human. Because the NAD 1 concentrations are determined by the balance of its synthesis and breakdown, measurement of the rates of the synthesis and breakdown are required to understand the mechanisms regulating the concentrations. For this purpose, incorporation of stable isotope-labeled precursors into NAD 1 should be quantified. We have analyzed NAD 1 formed from 2 H (D)-labeled precursors in mammalian cells using a liquid chromatographytandem mass spectrometry (LC/MS/MS) and found the cellular conversion of [2,4,5,6-D4]Nam (Fig. 1B) and [2,4,5,6-D4]NA (Fig. 1B) 1 has not directly been demonstrated. Furthermore, the mechanism for the 1-Da mass decrease in NAD 1 formed with the D4-labeled precursors in the cells remains unknown.In the cells, synthesized NAD 1 is reduced to NADH through the acceptance of an additional hydrogen (H) at the redox site (C-4 carbon of the pyridine ring), whereas the removal of either of the two H atoms at the redox site of NADH reforms NAD 1 (9, 10). The reversible transfer of H to and from either the pro-R or pro-S side at the redox site of NAD 1 /NADH is catalyzed by oxidoreductases exhibiting the opposite stereospecificity for the coenzymes (9, 10). We postulated that after the synthesis of [Nam-2,4,5,6-D4]NAD 1 by NAD 1 biosynthetic enzymes in the cells, D at the C-4 carbon in its pyridine ring is exchanged with H through the cellular redox reactions of NAD 1 /NADH involving oxidoreductases, resulting in [Nam-2,5,6-D3]NAD 1 (Fig. 1C)

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“…Stereochemical studies on NADH produced by the HDH activity of a crude extract of Neurospora have been performed previously (Davies et al, 1972) and showed that the reaction was R(A) for both steps [UDPGDH is 5(B) for both steps, f This research was supported by grants from the NSF (DMB87-05583). The NMR Facility at New York University is supported by grants from the NIH and the NYU Cost-Sharing Instrumentation Fund. 0006-2960/89/0428-8174S01.50/0 and HMGR is R(A) for both steps; You, 1982]. However, HDH from yeast is known to be a multifunctional enzyme (Donahue et al, 1982), and the recent finding of opposite stereochemistry at NADH for liver and Drosophila ADH (Benner et al, 1985) suggested that additional stereochemical studies on HDH from Salmonella were important.…”

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confidence: 99%

Salmonella typhimurium histidinol dehydrogenase: complete reaction stereochemistry and active site mapping

Grubmeyer¹,

Insinga²,

Bhatia³

et al. 1989

Biochemistry

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The stereochemistry of the L-histidinol dehydrogenase reaction was determined to be R at NAD for both steps, confirming previous results with a fungal extract [Davies, D., Teixeira, A., & Kenworthy, P. (1972) Biochem. J. 127, 335-343]. NMR analysis of monodeuteriohistidinols produced by histidinol/NADH exchange reactions arising via reversal of the alcohol oxidation reaction indicated a single stereochemistry at histidinol for that step. Comparison of vicinal coupling values of the exchange products with those of L-alaninol and a series of (S)-2-amino-1-alcohols allowed identification of the absolute stereochemistry of monodeuteriohistidinols and showed that histidinol dehydrogenase removes first the pro-S then the pro-R hydrogens of substrate histidinol. The enzyme stereochemistry was confirmed by isotope effects for monodeuteriohistidinols as substrates for the pro-R-specific dehydrogenation catalyzed by liver alcohol dehydrogenase. Active site mapping was undertaken to investigate substrate-protein interactions elsewhere in the histidinol binding site. Critical binding regions are the side-chain amino group and the imidazole ring, whose methylation at the 1- or 2-position caused severe decreases in binding affinity. Use of alternative substrates further clarified active site interactions with the substrate. Compounds in which the alpha-amino group was replaced by chloro, bromo, or hydrogen substituents were not substrates of the overall reaction at 1/10,000 the normal rate.(ABSTRACT TRUNCATED AT 250 WORDS)

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[9] Stereospecificities of the pyridine nucleotide-linked enzymes

Cited by 42 publications

References 125 publications

Stereochemical course of two arene-cis-diol dehydrogenases specifically induced in Pseudomonas putida

Stereochemical course of two arene-cis-diol dehydrogenases specifically induced in Pseudomonas putida

Formation of [Nicotinamide-2H3]NAD+ from [2H4]Nicotinamide and [2H4]Nicotinic Acid in Human HepG2N Cells and Involvement of 2H/1H Exchange at the Redox Site of NAD+/NADH

Salmonella typhimurium histidinol dehydrogenase: complete reaction stereochemistry and active site mapping

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