High homocysteine induces betaine depletion.

Abstract

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.

• Authors: Apolline Imbard, Jean-François Benoist, Ruben Esse, Sapna Gupta, Sophie Lebon, An S de Vriese, Helene Ogier de Baulny, Warren Kruger, Manuel Schiff, Henk J Blom
• Journal: Bioscience reports (Biosci Rep) Vol. 35 Issue 4 (Apr 28 2015) ISSN: 1573-4935 [Electronic] England
• PMID: 26182429 (Publication Type: Journal Article)
• Copyright: © 2015 Author(s).

Chemical References

• Carrier Proteins
• GABA Plasma Membrane Transport Proteins
• Slc6a12 protein, mouse
• Homocysteine
• betaine plasma membrane transport proteins
• Betaine
• BHMT protein, human
• Betaine-Homocysteine S-Methyltransferase
• Bhmt protein, mouse
• Bhmt protein, rat

Topics

• Animals
• Betaine (blood)
• Betaine-Homocysteine S-Methyltransferase (genetics, metabolism)
• Carrier Proteins (genetics, metabolism)
• Disease Models, Animal
• Female
• GABA Plasma Membrane Transport Proteins (genetics, metabolism)
• Homocysteine (blood, genetics)
• Homocystinuria (blood, genetics)
• Humans
• Male
• Mice
• Mice, Transgenic
• Rats
• Rats, Wistar