S-adenosylmethionine Metabolism and AFP Expression: Is There a Direct Link?

The parallel behavior of AFP and methionine serum levels in hereditary tyrosinemia has led to the hypothesis that methionine activation and AFP expression are functionally related. The present study was conducted to test this idea. The preliminary experiments reported here were primarily designed to test whether AFP production and methionine adenosyltransferase activity change coordinately during normal development, and whether factors (hormones, injury) which influence AFP production in newborn or adult livers exert a coordinate effect on methionine adenosyltransferase activity or S-adenosylmethionine pool or vice versa. Some other data are included that relate to the problem, in particular, the serum methionine and AFP levels in children with Indian Childhood Cirrhosis, and the AFP levels in the first days of 3′M-DAB feeding in rats. The sum of our observations provides little support at this point to the concept of differentiation control at the methionine activation step. If any common denominator exists that promotes AFP production in several liver conditions, and accounts for parallel methionine-AFP modulations as observed in hereditary tyrosinemia, a more likely candidate might be an acute depletion of liver ATP pool.