Regulation of Yeast Phosphatidate Phosphatase by Fatty Acids

Abstract

The PAH1‐encoded phosphatidate (PA) phosphatase in Saccharomyces cerevisiae is a pivotal enzyme that produces diacylglycerol for the synthesis of the storage lipid triacylglycerol (TAG), and simultaneously controls the level of PA used for phospholipid synthesis. PA phosphatase activity is induced by exogenous fatty acids and this induction is critical for protecting the cells from the toxic effects exerted by fatty acids. Indeed, PA phosphatase channels the fatty acids to TAG thereby neutralizing them. In this work, we show that the level of PA phosphatase induction depends on the fatty acid species supplied to the cells, with palmitoleic acid (C16:1) being the most potent inducer. Lipid analysis showed that cells grown in the presence of palmitoleic acid present a massive induction of TAG accumulation, as opposed to cells grown in the presence of either palmitic (C16:0), stearic (C18:0) or oleic (C18:1) acid. This discrepancy could be because palmitoleic acid gets incorporated much more efficiently than the rest of the fatty acids. This notion is supported by the fatty acid profile of lipids in cells supplied with palmitoleic acid where this fatty acid becomes more than 80% (w/w) of the total cellular fatty acids. In contrast, supplementation with either palmitic, stearic or oleic acid causes a less pronounced effect on cellular lipids (i.e. 45% (w/w)). Supported by NIH grant GM‐28140.