Low activity of mitochondrial HMG-CoA synthase in liver of starved pigletsis due to low levels of protein despite high mRNA levels

The unusually low hepatic ketogenic capacity of piglets has been correlated with lack of expression of the mitochondrial HMG-CoA synthase gene. Howeve r, we have shown that starvation of 2-week-old piglets increased the mRNA l evels of mitochondrial HMG-CoA synthase to a level similar to that observed in starved rats (S, H. Adams, C, S, Alho, G. Asins, F. G, Hegardt, and P. F, Marrero, 1997, Biochem, J, 324, 65-73). We now report that antibodies ag ainst pig mitochondrial HMG-CoA synthase detected the pig enzyme in mitocho ndria of a-week-old starved piglets and that the pig mitochondrial HMG-CoA synthase cDNA encodes an active enzyme in the eukaryotic cell line Mev-1, w ith catalytic behavior similar to that of the rat enzyme when expressed in the same system. We also show that low activity of pig mitochondrial HMG-Co A synthase correlates with low expression of the pig enzyme. The discrepanc y in mitochondrial HMG-CoA synthase gene expression between the high levels of mRNA and low levels of enzyme was not associated with differences in tr anscript maturation, which suggests that an attenuated translation of the p ig mRNA is responsible for the diminished ketogenic capacity of pig mitocho ndria, (C) 2001 Academic Press.