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Imbard A , Benoist JF , Esse R , Gupta S , Lebon S , de Vriese AS , de Baulny HO , Kruger W , Schiff M , Blom HJ
High homocysteine induces betaine depletion
Biosci Rep. 2015 Apr 28;35(4)
PMID: 26182429    PMCID: PMC4613678    URL: http://www.ncbi.nlm.nih.gov/pubmed/26182429
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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 beta-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.
Imbard, Apolline Benoist, Jean-Francois Esse, Ruben Gupta, Sapna Lebon, Sophie de Vriese, An S de Baulny, Helene Ogier Kruger, Warren Schiff, Manuel Blom, Henk J England Biosci Rep. 2015 Apr 28;35(4). pii: e00222. doi: 10.1042/BSR20150094.