Hepatic cystathionine beta-synthase activity does not increase in response to methionine supplementation in rats fed a low casein diet: association with plasma homocysteine concentrations.

To elucidate the mechanism by which moderate and high protein diets fail to increase plasma homocysteine concentration despite dietary methionine levels being higher, rats were fed diets with graded levels (10, 30, and 50%) of casein or low casein diets supplemented with methionine at levels of 0.5 and 1.0% together with or without glycine+serine, which corresponded to moderate and high casein diets with respect to these amino acids, for 14 d. The plasma homocysteine concentration significantly decreased with an increase in dietary casein level, whereas it significantly increased with an increase in dietary methionine level when the low casein diet was supplemented with methionine. Supplementation with glycine+serine significantly suppressed the elevation of plasma homocysteine concentration due to methionine supplementation, but it could not decrease plasma homocysteine concentration to the levels in rats fed corresponding casein diets. Increased concentrations of hepatic S-adenosylhomocysteine and homocysteine due to methionine supplementation were also significantly suppressed by glycine+serine. The activity of hepatic cystathionine beta-synthase (CBS) did not increase in response to methionine supplementation, while it significantly increased with an increase in dietary casein level. In contrast, the activity of hepatic betaine-homocysteine S-methyltransferase (BHMT) significantly increased with increase in both dietary casein level and dietary methionine level. Hepatic levels of mRNA for CBS and BHMT were parallel to the enzyme activities. The results suggest that, in contrast to methionine-supplemented low casein diets, moderate and high casein diets avoid increasing plasma homocysteine concentration through dual mechanisms, greater supply of glycine+serine and an increase in CBS activity.