Methionine deficiency increases betaine-homocysteine methyltransferase (BHMT) activity and mRNA levels in rat liver

BHMT activity has been shown to fluctuate due to changes in the dietary intake of sulfur amino acids, choline, and betaine. We recently cloned mammalian cDNAs encoding BHMT, and to test whether changes in BHMT activity are mediated by changes in BHMT mRNA levels, we monitored hepatic BHMT activity and mRNA content of rats fed diets containing either adequate (0.3%) or deficient (0.1%) levels of methionine, adequate (0.3%) or supplemental (0.6%) levels of cystine, and either devoid or containing betaine (25 mmol/kg), dimethylacetothetin (37.5 mmol/kg), or dimethylpropiothetin (37.5 mmol/kg). All diets contained 5 mmol/kg choline. We used weaning rats and monitored growth and food intake for two weeks. Rats consuming the methionine deficient diets gained weight, indicating that methionine was above maintenance level. Our results show that methionine deficiency significantly increases steady-state levels of hepatic BHMT mRNA, and excess dietary betaine or thetin, concomitant with methionine deficiency, elevates BHMT mRNA levels even further than that observed for methionine deficiency alone. Dietary cystine had no effect on BHMT mRNA levels. Hepatic BHMT activity levels mirrored BHMT mRNA content.