Phenylalanine hydroxylase expression in primary rat hepatocytes is modulated by oxygen concentration

In this work we have investigated the regulation of rat phenylalanine hydroxylase (rPAH) expression by oxygen in primary cultures of rat hepatocytes. We show that rPAH is negatively modulated at the mRNA, protein and activity levels by pO₂ of 16% (periportal hepatic levels) compared to 8% (perivenous hepatic levels). Our results suggest that PAH might be metabolically zonated in vivo, and preferentially found in perivenous hepatocytes with high glucose consumption and largely influenced by insulin levels.