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ACSBG2 is a Testis‐ and Brainstem‐Specific Homolog of the Acyl‐CoA Synthetase “Bubblegum”
Author(s) -
Pei Zhengtong,
Jia Zhenzhen,
Watkins Paul
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a949-b
Subject(s) - enzyme , histidine , biochemistry , biology , mutant , microbiology and biotechnology , arginine , enzyme assay , chemistry , gene , amino acid
The defective gene in the Drosophila mutant “bubblegum” encodes ACSBG1, an acyl‐CoA synthetase (ACS) whose properties have implicated it in the biochemical pathology of the genetic neurodegenerative disorder, X‐linked adrenoleukodystrophy. We cloned and characterized a homologous enzyme, ACSBG2, and investigated its properties. ACSBG2 was found only in Sertoli cells of the testis and large motoneurons of the medulla oblongata and cervical spinal cord. ACSBG2 was found in the microsome‐enriched fraction of mouse testis fractionated by differential centrifugation. When expressed in COS‐1 cells, the enzyme activated only oleic (C18:1) and linoleic (C18:2) acid substrates. The activity of human ACSBG2 was lower than that of mouse ACSBG2 when assayed at pH 7.5. We noted that a conserved active site arginine residue was in fact a histidine in the human enzyme. Examination of the pH profile of C18:1 activation revealed that the pH optimum of the human enzyme was about 6.5. In contrast, the mouse enzyme was most active at pH 7.0‐7.5. We mutated the active site histidine to arginine in human ACSBG2 and observed a shift in the pH optimum to that of the mouse enzyme. We hypothesize that this naturally occurring mutation affects catalytic function of the endogenous human enzyme. Further studies to characterize the role of ACSBG2 in testis and brainstem lipid metabolism are in progress. Supported by NIH grants NS37355 and HD10981.