(676.13) Alcohol and L-3-hydroxyacyl-CoA dehydrogenases activities of human Aβ-binding alcohol dehydrogenase and type 10 17β-hydroxysteroid dehydrogenase

Poster Board Number: A437

Xue-Ying He (NYS Institute for Basic Research), Carl Dobkin (NYS Institute for Basic Research), W. Ted Brown (University of Sydney), Song-Yu Yang (NYS Institute for Basic Research, Graduate School City Univ of New York)

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is a mitochondrial homo-tetrameric protein necessary for brain cognitive function. It was first isolated as a human brain short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), of which the primary structure is almost identical with that of endoplasmic reticulum associated Aβ binding protein (ERAB). The finding of generalized alcohol dehydrogenase activities in ERAB prompted its renaming as the Aβ-peptide binding alcohol dehydrogenase (ABAD).  Both reflect some dubious features of 17β-HSD10 and recognized as alternative symbols of 17β-HSD10, even if they were just a subunit of 17β-HSD10 only. 17β-HSD10 was encoded by HSD17B10 gene whose mutations resulted in developmental disabilities such as infantile neurodegeneration. A 6xHis-tag adding at the N-terminus of 17β-HSD10 would not substantially affect its catalytic function. Desired 6xHis-HSD10 mutants can be readily made to study how a mutation not only interfering the neurosteroid metabolism but also the metabolism of acyl thioesters. Results of this study indicated that 17β-HSD10 was not involved in the ketone body metabolism. Furthermore, it is impossible for anyone to reproduce the published generalized alcohol dehydrogenase data. The clarification of the confused ABAD story may invigorate this research field, and open new approaches to investigate HSD17B10 gene-related disorders including developmental disabilities, Parkinson disease, Alzheimer disease and some cancers.

NYS Office for People With Developmental Disabilities