Inactivation of glyceraldehyde-3-phosphate dehydrogenase by the dopamine metabolite, 3,4-dihydroxyphenylacetaldehyde

Brigitte C. Vanle, Virginia R. Florang, Daryl J Murry, Arturo L. Aguirre, Jonathan A. Doorn

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background The aldehyde metabolite of dopamine, 3,4-dihydroxyphenylacetaldehyde (DOPAL) is an endogenous neurotoxin implicated in Parkinson's Disease. Elucidating protein targets of DOPAL is essential in understanding it's pathology. The enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a target of DOPAL. Methods GAPDH activity was measured via reduction of NAD+ cofactor (340 nm). Protein aggregation was assessed with SDS-PAGE methods and specific modification via chemical probes. Results Low micromolar levels of DOPAL caused extensive GAPDH aggregation and irreversibly inhibited enzyme activity. The inactivation of GAPDH was dependent on both the catechol and aldehyde moieties of DOPAL. It is suggested that Cys are modified and oxidized by DOPAL. Conclusions The mechanism by which DOPAL modifies GAPDH can serve as a mechanistic explanation to the pathological events in Parkinson's Disease.

Original languageEnglish (US)
Pages (from-to)275-281
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume492
Issue number2
DOIs
StatePublished - Oct 14 2017
Externally publishedYes

Fingerprint

Glyceraldehyde-3-Phosphate Dehydrogenases
Metabolites
Dopamine
Aldehydes
Parkinson Disease
Agglomeration
Neurotoxins
Enzyme activity
Pathology
Enzymes
NAD
Polyacrylamide Gel Electrophoresis
Proteins
3,4-dihydroxyphenylacetaldehyde

Keywords

  • 3,4-Dihydroxyphenylacetaldehyde
  • Biogenic aldehyde
  • Glyceraldehyde-3-phosphate dehydrogenase
  • Parkinson's disease

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Inactivation of glyceraldehyde-3-phosphate dehydrogenase by the dopamine metabolite, 3,4-dihydroxyphenylacetaldehyde. / Vanle, Brigitte C.; Florang, Virginia R.; Murry, Daryl J; Aguirre, Arturo L.; Doorn, Jonathan A.

In: Biochemical and Biophysical Research Communications, Vol. 492, No. 2, 14.10.2017, p. 275-281.

Research output: Contribution to journalArticle

Vanle, Brigitte C. ; Florang, Virginia R. ; Murry, Daryl J ; Aguirre, Arturo L. ; Doorn, Jonathan A. / Inactivation of glyceraldehyde-3-phosphate dehydrogenase by the dopamine metabolite, 3,4-dihydroxyphenylacetaldehyde. In: Biochemical and Biophysical Research Communications. 2017 ; Vol. 492, No. 2. pp. 275-281.
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AU - Doorn, Jonathan A.

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