Excess leucine intake effects on asparagine synthetase and 3‐phosphoglycerate dehydrogenase expression in the liver of rats fed a low‐protein diet (820.13)

Abstract

De novo synthesis of dispensable amino acids such as asparagine and serine is crucial for cell growth and function. We found that asparagine synthetase (AS), 3‐phosphoglycerate dehydrogenase (PHGDH, key enzyme for serine biosynthesis), and serine dehydratase (SDH, serine degradative enzyme) expression in rat liver were tightly regulated in response to the protein requirement. Thus, AS and PHGDH were induced through a low‐protein diet, below rat’s protein requirement, whereas SDH was induced through a high‐protein diet, above their requirement. However, we observed that SDH was also induced by leucine ingestion. Excess leucine intake through a low‐protein diet causes severe growth retardation in rat. We here examined the effect of dietary leucine on AS, PHGDH, and SDH expression with regard to growth retardation. Male rats were divided into 12 groups and fed for one week a diet containing low, moderate or high protein. Different levels of leucine (0, 2, 4, and 8%) were added to the diets. The results demonstrated that AS and PHGDH expression was dose‐dependently suppressed in rat liver, whereas SDH expression increased when rats were maintained on a low‐protein diet. Body weight and food intake concomitantly decreased. Valine and isoleucine affected neither gene expression nor food intake and body weight. These results suggested that leucine suppressed AS and PHGDH expression and could cause growth retardation.