Betaine is the substrate of the liver- and kidney-specific
betaine-
homocysteine (Hcy)
methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for
homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured
betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of
cystathionine β-synthase (
CBS) deficiency. S-adenosyl-
methionine (
AdoMet), S-adenosyl-
homocysteine (AdoHcy),
methionine,
betaine and
dimethylglycine (DMG) were quantified by ESI-LC-MS/MS.
mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma
betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model,
betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse
CBS deficiency model,
betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces
betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body
betaine pool. In kidney,
betaine concentrations were not affected, possibly due to overexpression of the
betaine transporter SLC6A12 where
betaine may be conserved because of its crucial role as an osmolyte.