Roles for ACAD10 and Mouse ACAD12

Identification of Roles for ACAD10 and Mouse ACAD12 in Physiology

ACAD10 has been implicated in diabetes in humans. ACAD10 knockout mice experiments confirmed a relationship. Although ACAD10 has an ACAD domain very similar to the ACAD family of flavoenzymes, it also has an extra-large domain that we have hypothesized is an electron transfer domain that likely binds nicotinamide adenine dinucleotide (NAD). Moreover, its active site according to the crystal structure of ACAD11 and modeling seem to contain basic residues, implying possibly more than just a α,β-dehydrogenation biochemical function, but perhaps other function comparable to glutaryl-CoA dehydrogenase, which has an additional decarboxylation function. Our latest expression studies in insect cells indicate that a greater than 110 Kd protein and another 48 Kd species could be expressed from the full-length gene cloned in the expression vector. Insect cells expressing the protein(s) will be soon grown in bulk to attempt to purify them and characterize them. Another exciting result from the investigations of ACAD10 in mice is the confirmation of the presence of another ACAD protein, ACAD12. This one is surprisingly very similar to a short peptide at the N-terminus, ~160 amino acids, plus the ACAD domain of ACAD10 to almost 97 percent homology. Our lab is currently pursuing the identification of the function of this version of an ACAD.

Principal Investigator

Al-Walid A. Mohsen, PhD