Neurochemical Research

, Volume 32, Issue 4, pp 871–891

Enzyme-Catalyzed Side Reactions with Molecular Oxygen may Contribute to Cell Signaling and Neurodegenerative Diseases

  • Victoria I. Bunik
  • John V. Schloss
  • John T. Pinto
  • Gary E. Gibson
  • Arthur J. L. Cooper
Original Paper

DOI: 10.1007/s11064-006-9239-z

Cite this article as:
Bunik, V.I., Schloss, J.V., Pinto, J.T. et al. Neurochem Res (2007) 32: 871. doi:10.1007/s11064-006-9239-z

Abstract

A link between neurodegeneration and well-characterized enzymatic and non-enzymatic reactions that produce reactive oxygen species (ROS) from O2 is well established. Several enzymes that contain pyridoxal 5′-phosphate (PLP) or thiamine diphosphate (ThDP) catalyze side reactions (paracatalytic reactions) in the presence of ambient O2. These side reactions produce oxidants such as hydrogen peroxide [H2O2] or extremely reactive peracids [RC(O)OOH]. We hypothesize that although these enzymes normally produce oxidants at low or undetectable levels, changes in substrate levels or disease-induced structural alterations may enhance interactions with O2, thereby generating higher levels of reactive oxidants. These oxidants may damage the enzymes producing them, alter nearby macromolecules and/or destroy important metabolites/coenzymes. We propose that paracatalytic reactions with O2 catalyzed by PLP-dependent decarboxylases and by ThDP-dependent enzymes within the α-keto acid dehydrogenase complexes may contribute to normal cellular signaling and to cellular damage in neurodegenerative diseases.

Keywords

Branched chain α-keto acid dehydrogenase complex Carbanion intermediates α-Ketoglutarate dehydrogenase complex Pyridoxal 5′-phosphate Pyruvate dehydrogenase complex Thiamine diphosphate 

Abbreviations

AD

Alzheimer disease

ALS II

Acetolactate synthase isozyme II

BCKADC

Branched chain α-keto acid dehydrogenase complex

CSAD

Cysteine sulfinic acid decarboxylase

DDC

Dopa decarboxylase

dopal

3,4-dihydroxyphenylacetaldehyde

E1b

Branched-chain α-keto acid dehydrogenase

E1k

α-Ketoglutarate dehydrogenase

E1p

Pyruvate dehydrogenase

E2k

Dihydrolipoamide succinyl transferase

E3

Dihydrolipoamide dehydrogenase

GABA

γ-Aminobutyric acid

GAD

Glutamate decarboxylase

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

GSH

Glutathione

GSSG

Glutathione disulfide

KG

α-Ketoglutarate

KGDHC

α-Ketoglutarate dehydrogenase complex

ODC

Ornithine decarboxylase

PAAS

Phenylacetaldehyde synthase

PDHC

Pyruvate dehydrogenase complex

PLP

Pyridoxal 5′-phosphate

PMP

Pyridoxamine 5′-phosphate

ROS

Reactive oxygen species

RNS

Reactive nitrogen species

Rubisco

Ribulose 1,5-bisphosphate carboxylase/oxygenase

SOD

Superoxide dismutase

TCA

Tricarboxylic acid

ThDP

Thiamine diphosphate

TNB

5-Thionitrobenzoate

Tx

Thioredoxin

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Victoria I. Bunik
    • 1
  • John V. Schloss
    • 2
  • John T. Pinto
    • 3
  • Gary E. Gibson
    • 3
    • 4
  • Arthur J. L. Cooper
    • 3
    • 4
    • 5
  1. 1.School of Bioengineering and Bioinformatics, and Belozersky Institute of Physico-Chemical BiologyMoscow State UniversityMoscowRussia
  2. 2.NeuroSystecValenciaUSA
  3. 3.Burke Medical Research InstituteWhite PlainsUSA
  4. 4.Department of Neurology and NeuroscienceWeill Medical College of Cornell University New YorkUSA
  5. 5.Department of BiochemistryWeill Medical College of Cornell UniversityNew YorkUSA

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