Amyloid β-peptide-binding alcohol dehydrogenase is a component of the cellular response to nutritional stress

Shi Du Yan, Yucui Zhu, Eric D. Stern, Yuying C. Hwang, Osamu Hori, Satoshi Ogawa, Matthew P. Frosch, E. Sander Connolly, Ryan McTaggert, David J. Pinsky, Steven Clarke, David Stern, Ravichandran Ramasamy

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Abstract

Amyloid β-peptide-binding alcohol dehydrogenase (ABAD) is a member of the family of short chain dehydrogenase/reductases whose distinctive properties include the capacity to bind amyloid β-peptide and enzymatic activity toward a broad array of substrates including n-isopropanol and β-estradiol. In view of the wide substrate specificity of ABAD and its high activity on L-β-hydroxyacyl-CoA derivatives, we asked whether it might also catalyze the oxidation of the ketone body D-3-hydroxybutyrate. This was indeed the case, and oxidation proceeded with K(m) of ~4.5 mM and V(max) of ~4 nmol/min/mg protein. When placed in medium with D-β-hydroxybutyrate as the principal energy substrate, COS cells stably transfected to overexpress wild-type ABAD (COS/wtABAD) better maintained 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction, cellular energy charge, and morphologic phenotype compared with COS/vector cells. Using a severe model of metabolic perturbation, transgenic mice with targeted neuronal expression of ABAD subjected to transient middle cerebral artery occlusion showed strokes of smaller volume and lower neurologic deficit scores in parallel with increased brain ATP and decreased lactate, compared with nontransgenic controls. These data suggest that ABAD contributes to the protective response to metabolic stress, especially in the setting of ischemia.

Original languageEnglish (US)
Pages (from-to)27100-27109
Number of pages10
JournalJournal of Biological Chemistry
Volume275
Issue number35
DOIs
StatePublished - Sep 1 2000
Externally publishedYes

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Alcohol Dehydrogenase
Amyloid
Peptides
COS Cells
Oxidoreductases
Substrates
Hydroxybutyrates
Ketone Bodies
Oxidation
Physiological Stress
3-Hydroxybutyric Acid
2-Propanol
Middle Cerebral Artery Infarction
Coenzyme A
Substrate Specificity
Neurologic Manifestations
Stroke Volume
Transgenic Mice
Estradiol
Lactic Acid

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Yan, S. D., Zhu, Y., Stern, E. D., Hwang, Y. C., Hori, O., Ogawa, S., ... Ramasamy, R. (2000). Amyloid β-peptide-binding alcohol dehydrogenase is a component of the cellular response to nutritional stress. Journal of Biological Chemistry, 275(35), 27100-27109. https://doi.org/10.1074/jbc.M000055200

Amyloid β-peptide-binding alcohol dehydrogenase is a component of the cellular response to nutritional stress. / Yan, Shi Du; Zhu, Yucui; Stern, Eric D.; Hwang, Yuying C.; Hori, Osamu; Ogawa, Satoshi; Frosch, Matthew P.; Connolly, E. Sander; McTaggert, Ryan; Pinsky, David J.; Clarke, Steven; Stern, David; Ramasamy, Ravichandran.

In: Journal of Biological Chemistry, Vol. 275, No. 35, 01.09.2000, p. 27100-27109.

Research output: Contribution to journalArticle

Yan, SD, Zhu, Y, Stern, ED, Hwang, YC, Hori, O, Ogawa, S, Frosch, MP, Connolly, ES, McTaggert, R, Pinsky, DJ, Clarke, S, Stern, D & Ramasamy, R 2000, 'Amyloid β-peptide-binding alcohol dehydrogenase is a component of the cellular response to nutritional stress', Journal of Biological Chemistry, vol. 275, no. 35, pp. 27100-27109. https://doi.org/10.1074/jbc.M000055200
Yan, Shi Du ; Zhu, Yucui ; Stern, Eric D. ; Hwang, Yuying C. ; Hori, Osamu ; Ogawa, Satoshi ; Frosch, Matthew P. ; Connolly, E. Sander ; McTaggert, Ryan ; Pinsky, David J. ; Clarke, Steven ; Stern, David ; Ramasamy, Ravichandran. / Amyloid β-peptide-binding alcohol dehydrogenase is a component of the cellular response to nutritional stress. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 35. pp. 27100-27109.
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