Adenosylcobalamin-dependent glycerol dehydratase interaction with substrates and their analogs

Poznanskaya, A. A.; Korsova, T. L.

doi:10.1515/9783111510828-039

Cited by 4 publications

(2 citation statements)

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“…However, the rate constant for inactivation of diol dehydratase by glycerol (1.3 min-1) differs significantly from that for glycerol dehydratase (0.35 min-1) (Poznanskaya et al, 1972). Thus, the main kinetic difference between the two enzymes may be a greater rate for the inactivation of diol dehydratase by glycerol than for the inactivation of glycerol dehydratase; in other respects, these two enzymes are even more similar than previously thought.…”

Section: Discussionmentioning

confidence: 71%

Mechanism of action of adenosylcobalamin: glycerol and other substrate analogs as substrates and inactivators for propanediol dehydratase - kinetics, stereospecificity, and mechanism

Bachovchin¹,

Eagar²,

Moore³

et al. 1977

Biochemistry

105

133

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A number of vicinal diols were found to react with propanediol dehydratase, typically resulting in the conversion of enzyme-bound adenosylcobalamin to cob(II)alamin and formation of aldehyde or ketone derives from substrate. Moreover, all are capable of effecting the irreversible inactivation of the enzyme. The kinetics and mechanism of product formation and inactivation were investigated. Glycerol, found to be a very good substrate for diol dehydratase as well as a potent inactivator, atypically, did not induce cob(II)alamin formation to any detectable extent. With glycerol, the inactivation process was accompanied by conversion of enzyme-bound adenosylcobalamin to an alkyl or thiol cobalamin, probably by substitution of an amino acid chain near the active site for the 5'-deoxy-5'-adenosyl ligand on the cobalamin. The inactivation reaction with glycerol as the inactivator exhibits a deuterium isotope effect of 14, strongly implicating hydrogen transfer as an important step in the mechanism of inactivation. The isotope effect on the rate of product formation was found to be 8.0. Experiments with isotopically substituted glycerols indicate that diol dehydrase distinguishes between "R" and "S" binding conformations, the enzyme-(R)-glycerol complex being predominately responsible for the product-forming reaction, while the enzyme-(S)-glycerol complex results primarily in the activation reaction. Mechanistic implications are discussed. A method for removing enzyme-bound hydroxycobalamin that is nondestructive to the enzyme and a technique for measuring the binding constants of (R)- and (S)-1,2-propanediols are presented.

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Section: Discussionmentioning

confidence: 71%

Mechanism of action of adenosylcobalamin: glycerol and other substrate analogs as substrates and inactivators for propanediol dehydratase - kinetics, stereospecificity, and mechanism

Bachovchin¹,

Eagar²,

Moore³

et al. 1977

Biochemistry

105

133

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“…Irreversible inactivation has been observed with ethylene glycol and diol dehydratase and with glycerol and glycerol dehydratase, although the inactivation rates are considerably slower than that of glycerol inactivation of diol dehydratase (Lee and Abeles, 1963;Poznanskaya et al, 1972). Thus, irreversible inactivation by substrate appears to be a rather common phenomenon associated with these enzymes and a study of its mechanism may advance our understanding of the normal catalytic mechanism.…”

mentioning

confidence: 99%

Mechanism of action of adenosylcobalamin: hydrogen transfer in the inactivation of diol dehydratase by glycerol

Bachovchin¹,

Moore²,

Richards³

1978

Biochemistry

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We have investigated the kinetic characteristics of the inactivation of the adenosylcobalamin-dependent enzyme propanediol dehydratase by glycerol, (RS)-1,1-dideuterioglycerol, (R)-1,1-dideuterioglycerol, and perdeuterioglycerol in the presence of 1,2-propanediol and 1,1-dideuterio-1,2-propanediol. The results imply that hydrogen (or deuterium) attached to C-1 of 1,2-propanediol participates in the inactivation process and contributes to the expression of a kinetic isotope effect on the rate of inactivation. The mechanism for this inactivation must involve the cofactor as an intermediate hydrogen carrier, presumably in the form of 5'-deoxyadenosine. Moreover, a mechanism involving a rate-determining transfer of hydrogen from an intermediate containing three equivalent hydrogens quantitatively accounts for all of the results. When diol dehydratase holoenzyme is inactivated by [1-3H]glycerol, 5'-deoxyadenosine which is enriched in tritium by a factor of 2.1 over that in glycerol can be isolated from the reaction mixture.

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Vitamin B12 als biologisch aktive Modellsubstanz

Zagalak

1982

Naturwissenschaften

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A critical review on corrinoid biochemistry and physiology is presented. This includes: chemical synthesis of biologically important organocorrinoids and the correlation between their structures and coenzymatic activity; forms, distribution and transport of physiologically active corrinoids; methylcobalamin- and adenosylcobalamin-dependent enzymatic reactions and their physiological functions; and steric course of the adenosylcobalamin-dependent enzymatic rearrangements. Special attention is paid to the mechanisms of adenosylcobalamin-dependent enzymatic reactions.

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Adenosylcobalamin-dependent glycerol dehydratase interaction with substrates and their analogs

Cited by 4 publications

References 0 publications

Mechanism of action of adenosylcobalamin: glycerol and other substrate analogs as substrates and inactivators for propanediol dehydratase - kinetics, stereospecificity, and mechanism

Mechanism of action of adenosylcobalamin: glycerol and other substrate analogs as substrates and inactivators for propanediol dehydratase - kinetics, stereospecificity, and mechanism

Mechanism of action of adenosylcobalamin: hydrogen transfer in the inactivation of diol dehydratase by glycerol

Vitamin B12 als biologisch aktive Modellsubstanz

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