Role of nascent α-ketoaldehyde in substrate-dependent oxidative inactivation of aldolase

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Abstract

In the presence of electron acceptors rabbit muscle aldolase catalyzes the oxidation of dihydroxyacetone phosphate and in the course of this activity the enzyme is progressively inactivated. It is proposed that the agent responsible for inactivation is the highly electrophilic α-ketoaldehyde produced in the reaction. This ketoaldehyde is herein shown to react rapidly with arginine side-chains, forming stable adducts, and with an active center residue in aldolase, leading to inactivation of the enzyme. Substrate-dependent oxidative inactivation of aldolase is brought about by reaction in situ of hydroxypyruvaldehyde phosphate with the essential residue located in the active site. The role of nascent hydroxypyruvaldehyde phosphate in aldolase inactivation is also borne out by studies with the substrate analogue D-5-ketofructose 1,6-bisphosphate. Cleavage of this hexose bisphosphate by aldolase yields hydroxypyruvaldehyde phosphate in the absence of any oxidant and, as in the case of oxidative production of the ketoaldehyde, the catalytic cycles lead to inactivation of the enzyme. A similar role is suggested for nascent ketoaldehydes in the substrate-dependent oxidative inactivation of class II aldolase of yeast and transaldolase. Possible physiological significance of α-ketoaldehyde production is discussed.

Original languageEnglish
Pages (from-to)191-196
Number of pages6
JournalEuropean Journal of Biochemistry
Volume88
Issue number1
Publication statusPublished - 1978

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Fructose-Bisphosphate Aldolase
Substrates
Transaldolase
Enzymes
Dihydroxyacetone Phosphate
Hexoses
Oxidants
Yeast
Arginine
Muscle
Catalytic Domain
Yeasts
Electrons
Rabbits
Muscles
Oxidation
hydroxymethylglyoxal phosphate

ASJC Scopus subject areas

  • Biochemistry

Cite this

Role of nascent α-ketoaldehyde in substrate-dependent oxidative inactivation of aldolase. / Patthy, L.

In: European Journal of Biochemistry, Vol. 88, No. 1, 1978, p. 191-196.

Research output: Contribution to journalArticle

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abstract = "In the presence of electron acceptors rabbit muscle aldolase catalyzes the oxidation of dihydroxyacetone phosphate and in the course of this activity the enzyme is progressively inactivated. It is proposed that the agent responsible for inactivation is the highly electrophilic α-ketoaldehyde produced in the reaction. This ketoaldehyde is herein shown to react rapidly with arginine side-chains, forming stable adducts, and with an active center residue in aldolase, leading to inactivation of the enzyme. Substrate-dependent oxidative inactivation of aldolase is brought about by reaction in situ of hydroxypyruvaldehyde phosphate with the essential residue located in the active site. The role of nascent hydroxypyruvaldehyde phosphate in aldolase inactivation is also borne out by studies with the substrate analogue D-5-ketofructose 1,6-bisphosphate. Cleavage of this hexose bisphosphate by aldolase yields hydroxypyruvaldehyde phosphate in the absence of any oxidant and, as in the case of oxidative production of the ketoaldehyde, the catalytic cycles lead to inactivation of the enzyme. A similar role is suggested for nascent ketoaldehydes in the substrate-dependent oxidative inactivation of class II aldolase of yeast and transaldolase. Possible physiological significance of α-ketoaldehyde production is discussed.",
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N2 - In the presence of electron acceptors rabbit muscle aldolase catalyzes the oxidation of dihydroxyacetone phosphate and in the course of this activity the enzyme is progressively inactivated. It is proposed that the agent responsible for inactivation is the highly electrophilic α-ketoaldehyde produced in the reaction. This ketoaldehyde is herein shown to react rapidly with arginine side-chains, forming stable adducts, and with an active center residue in aldolase, leading to inactivation of the enzyme. Substrate-dependent oxidative inactivation of aldolase is brought about by reaction in situ of hydroxypyruvaldehyde phosphate with the essential residue located in the active site. The role of nascent hydroxypyruvaldehyde phosphate in aldolase inactivation is also borne out by studies with the substrate analogue D-5-ketofructose 1,6-bisphosphate. Cleavage of this hexose bisphosphate by aldolase yields hydroxypyruvaldehyde phosphate in the absence of any oxidant and, as in the case of oxidative production of the ketoaldehyde, the catalytic cycles lead to inactivation of the enzyme. A similar role is suggested for nascent ketoaldehydes in the substrate-dependent oxidative inactivation of class II aldolase of yeast and transaldolase. Possible physiological significance of α-ketoaldehyde production is discussed.

AB - In the presence of electron acceptors rabbit muscle aldolase catalyzes the oxidation of dihydroxyacetone phosphate and in the course of this activity the enzyme is progressively inactivated. It is proposed that the agent responsible for inactivation is the highly electrophilic α-ketoaldehyde produced in the reaction. This ketoaldehyde is herein shown to react rapidly with arginine side-chains, forming stable adducts, and with an active center residue in aldolase, leading to inactivation of the enzyme. Substrate-dependent oxidative inactivation of aldolase is brought about by reaction in situ of hydroxypyruvaldehyde phosphate with the essential residue located in the active site. The role of nascent hydroxypyruvaldehyde phosphate in aldolase inactivation is also borne out by studies with the substrate analogue D-5-ketofructose 1,6-bisphosphate. Cleavage of this hexose bisphosphate by aldolase yields hydroxypyruvaldehyde phosphate in the absence of any oxidant and, as in the case of oxidative production of the ketoaldehyde, the catalytic cycles lead to inactivation of the enzyme. A similar role is suggested for nascent ketoaldehydes in the substrate-dependent oxidative inactivation of class II aldolase of yeast and transaldolase. Possible physiological significance of α-ketoaldehyde production is discussed.

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