The resynthesis of methionine through betaine (BHMT) is confined to the liver and kidneys
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Intestinal metabolism of sulfur amino acids
"Because homocysteine methylation by betaine via betaine-homocysteine methyltransferase activity is confined to the liver and the kidney (3), choline and betaine dietary intake may have less impact on the methylation of homocysteine in the colon than folate since methionine synthase, that methylates homocysteine to methionine using 5-methyltetrahydrofolate as a methyl donor, is ubiquitously distributed (3). One of the consequences of folate deficiency is SAM deficiency since folate is involved in the remethylation of homocysteine to methionine, the precursor of SAM (
Fig. 1). However, folate supplementation can either prevent or exacerbate intestinal tumorigenesis, depending on the timing and dose of folate intervention (126). This may be explained by the function of folate in nucleotide synthesis (Fig. 1) where rapidly proliferating tissues, including tumours, have an increased requirement for nucleotides. At present, based on lack of compelling supportive evidence on the potential tumour-promoting effect and presence of some adverse effects (127, 128), a recent review concludes that folate supplementation should not be recommended as a chemopreventive measure against colorectal cancer (129)." -
"Betaine-homocysteine S-methyltransferase (BHMT) is the only enzyme known to catabolize betaine. In addition to being a substrate for BHMT, betaine also functions as an osmoprotectant that accumulates in the kidney medulla under conditions of high extracellular osmolarity. The mechanisms that regulate the partitioning of betaine between its use as a methyl donor and its accumulation as an osmoprotectant are not completely understood. The aim of this study was to determine whether BHMT expression is regulated by salt intake. This report shows that guinea pigs express BHMT in the liver, kidney, and pancreas and that the steady-state levels of BHMT mRNA in kidney and liver decrease 68% and 93% in guinea pigs consuming tap water containing high levels of salt compared with animals provided untreated tap water. The animals consuming the salt water also had ∼50% less BHMT activity in the liver and kidney, and steady-state protein levels decreased ∼30% in both organs. Pancreatic BHMT activity and protein levels were unaffected by the high salt treatment. The complex mechanisms involved in the downregulation of hepatic and renal BHMT expression in guinea pigs drinking salt water remain to be clarified, but the physiological significance of this downregulation may be to expedite the transport and accumulation of betaine into the kidney medulla under conditions of high extracellular osmolarity."
