Specific loss of the high-molecular-weight form of S-adenosyl-L-methionine synthetase in human liver cirrhosis.

We have measured the activity of S-adenosyl-L-methionine synthetase, the ratio between the high- and low-molecular-weight forms of this enzyme and the concentration of S-adenosyl-L-methionine in liver biopsies from a group of controls (n = 6) and in six cirrhotics (five posthepatitic and one alcoholic). The total activity of S-adenosyl-L-methionine synthetase was markedly reduced in cirrhosis (37.5% of that found in the control group). This was due to a specific reduction in the high-molecular-weight S-adenosyl-L-methionine synthetase in the group of cirrhotics (73.9 pmoles per min per mg protein) when compared with that observed in controls (460.3 pmoles per min per mg protein). Despite this reduction in the rate of synthesis of S-adenosyl-L-methionine (the high-molecular-weight form of the enzyme is 15 times more active than the low-molecular-weight form at physiological concentration of substrates), the concentration of this metabolite was the same in the control group (17.3 +/- 2.6 microM) and in the group of cirrhotics (17.8 +/- 3.1 microM). To explain these findings, it is postulated that in human liver, where the concentration of S-adenosyl-L-methionine is lower than the Km values of a variety of enzymes that use this metabolite (around 50 to 100 microM), a reduction in the synthesis of S-adenosyl-L-methionine is compensated by a reduction in the rate of utilization of this molecule without affecting the intrahepatic concentration of S-adenosyl-L-methionine.(ABSTRACT TRUNCATED AT 250 WORDS)