Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma

Background/Aims: It has been known for at least 50 years that alterations i n methionine metabolism occur in human liver cirrhosis. However, the molecu lar basis of this alteration is not completely understood, In order to gain more insight into the mechanisms behind this condition, mRNA levels of met hionine adenosyl-transferase (MAT1A), glycine methyltransferase (GNMT), met hionine synthase (MS), betaine homocysteine methyltransferase (BHMT) and cy stathionine beta -synthase (CBS) were examined in 26 cirrhotic livers, five hepatocellular carcinoma (HCC) tissues and ten control livers. Methods: The expression of the above-mentioned genes was determined by quan titative RT-PCR analysis. Methylation of MAT1A promoter was assessed by met hylation-sensitive restriction enzyme digestion of genomic DNA. Results: When compared to normal livers MAT1A, GNMT BHMT, CBS and MS mRNA c ontents were significantly reduced in liver cirrhosis, Interestingly, MAT1A promoter was hypermethylated in the cirrhotic liver. HCC tissues also show ed decreased mRNA levels of these enzymes. Conclusions: These findings establish that the abundance of the mRNA of the main genes involved in methionine metabolism is markedly reduced in human cirrhosis and HCC. Hypermethylation of MAT1A promoter could participate in its reduced expression in cirrhosis. These observations help to explain the hypermethioninemia, hyperhomocysteinemia and reduced hepatic glutathione c ontent observed in cirrhosis.