Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase.

Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase. Research Abstract Details 

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Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase. Abstract Text:

Gregory A Hunter,Junshun Zhang,Gloria C Ferreira,

5-Aminolevulinate synthase catalyzes the pyridoxal 5'-phosphate-dependent condensation of glycine and succinyl-CoA to produce carbon dioxide, CoA, and 5-aminolevulinate, in a reaction cycle involving the mechanistically unusual successive cleavage of two amino acid substrate alpha-carbon bonds. Single and multiple turnover rapid scanning stopped-flow experiments have been conducted from pH 6.8-9.2 and 5-35 degrees C, and the results, interpreted within the framework of the recently solved crystal structures, allow refined characterization of the central kinetic and chemical steps of the reaction cycle. Quinonoid intermediate formation occurs with an apparent pK(a) of 7.7 +/- 0.1, which is assigned to His-207 acid-catalyzed decarboxylation of the alpha-amino-beta-ketoadipate intermediate to form an enol that is in rapid equilibrium with the 5-aminolevulinate-bound quinonoid species. Quinonoid intermediate decay occurs in two kinetic steps, the first of which is acid-catalyzed with a pK(a) of 8.1 +/- 0.1, and is assigned to protonation of the enol by Lys-313 to generate the product-bound external aldimine. The second step of quinonoid decay defines k(cat) and is relatively pH-independent and is assigned to opening of the active site loop to allow ALA dissociation. The data support important refinements to both the chemical and kinetic mechanisms and indicate that 5-aminolevulinate synthase operates under the stereoelectronic control predicted by Dunathan's hypothesis.

Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase. Publishing Authors By Initials

GA Hunter,J Zhang,GC Ferreira,

For similar environment and public health: environment: environment, controlled: temperature research abstracts see: environment and public health: environment: environment, controlled: temperature research

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Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 23025-35

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 7

MONTH: 05

YEAR: 2007

Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase. Keywords Mesh Terms:

KEYWORDS: Temperature

MESH TERMS: chemistry

Chemical & Substance for Abstract: Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase. Information

Substance Name: 5-Aminolevulinate Synthetase

Registry Number: EC 2.3.1.37

Grant and Affiliation Information for Transient kinetic studies support refinements to the chemical and kinetic mechanisms of aminolevulinate synthase.

AFFILIATION: Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, Florida 33612-4799, USA. ghunter@health.usf.edu

Country: United States

AGENCY: United States NIDDK

GRANT: DK63191

ACRONYM: DK

MEDLINETA: J Biol Chem

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