Biotin regulates the genetic expression of holocarboxylase synthetase and mitochondrial carboxylases in rats

Biotin is the cofactor of carboxylases [pyruvate (PC), propionyl-CoA (PCC), 3-methyl crotonyl-CoA and acetyl-CoA], to which it is covalently bound by the action of holocarboxylase synthetase (HCS). We have studied whether bio tin also regulates their expression, as it does other, nonrelated enzymes ( e.g., glucokinase, phosphoenol pyruvate carboxykinase, guanylate cyclase). For this purpose, HCS, PC and PCC mRNAs were studied in biotin-deficient ra t liver, kidney, muscle and brain of biotin-deficient rats. PC- and PCC-spe cific activities and protein masses were also measured. The 24-h time cours e of HCS mRNA in deficient rats was examined after biotin supplementation. HCS mRNA was significantly reduced during vitamin deficiency. It increased in deficient rats after biotin was injected, reaching control levels 24 h a fter administration. These changes seem to be the first known instance in m ammals of an effect of a water-soluble vitamin on a mRNA functionally relat ed to it. In contrast, the decreased activities of the carboxylases were as sociated with reductions in the amounts of their enzyme proteins except in brain. However, their mRNA levels were not affected. There are no reports o n these types of vitamin affecting the mRNA or protein levels of their apoe nzymes or their products. This work provides evidence for biotin being a mo dulator of the genetic expression of the enzymes involved in its function a s a cofactor. As such, it may be a useful model for probing a similar role for other water-soluble vitamins.