PMID- 26182429
OWN - NLM
STAT- MEDLINE
DCOM- 20160411
LR  - 20220316
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 35
IP  - 4
DP  - 2015 Apr 28
TI  - High homocysteine induces betaine depletion.
LID - 10.1042/BSR20150094 [doi]
LID - e00222
AB  - 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.
CI  - (c) 2015 Author(s).
FAU - Imbard, Apolline
AU  - Imbard A
AD  - Biochemistry Hormonology Laboratory, Robert-Debre Hospital, APHP, 48 Bd Serurier, 
      Paris 75019, France Paris Sud University, Pharmacy Faculty, 5 rue Jean Baptiste 
      Clement, Chatenay-Malabry 92019, France apolline.imbard@rdb.aphp.fr.
FAU - Benoist, Jean-Francois
AU  - Benoist JF
AD  - Biochemistry Hormonology Laboratory, Robert-Debre Hospital, APHP, 48 Bd Serurier, 
      Paris 75019, France Paris Sud University, Pharmacy Faculty, 5 rue Jean Baptiste 
      Clement, Chatenay-Malabry 92019, France.
FAU - Esse, Ruben
AU  - Esse R
AD  - Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of 
      Pharmacy, University of Lisbon, Lisbon 1649-003, Portugal.
FAU - Gupta, Sapna
AU  - Gupta S
AD  - Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A.
FAU - Lebon, Sophie
AU  - Lebon S
AD  - INSERM UMR 1141, Hopital Robert Debre, 48 Bd Serurier, Paris 75019, France.
FAU - de Vriese, An S
AU  - de Vriese AS
AD  - Renal Unit, Department of Internal Medicine, AZ Sint-Jan AV, Bruges 8000, 
      Belgium.
FAU - de Baulny, Helene Ogier
AU  - de Baulny HO
AD  - *Reference Center for Inherited Metabolic Diseases, Robert-Debre Hospital, APHP, 
      Paris 75019, France.
FAU - Kruger, Warren
AU  - Kruger W
AD  - Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A.
FAU - Schiff, Manuel
AU  - Schiff M
AD  - INSERM UMR 1141, Hopital Robert Debre, 48 Bd Serurier, Paris 75019, France 
      *Reference Center for Inherited Metabolic Diseases, Robert-Debre Hospital, APHP, 
      Paris 75019, France daggerFaculte de Medecine Denis Diderot, Universite Paris 
      Diderot-Paris 7, Paris 75013, France.
FAU - Blom, Henk J
AU  - Blom HJ
AD  - double daggerLaboratory for Clinical Biochemistry and Metabolism, Department of General 
      Pediatrics, Center for Pediatrics and Adolescent Medicine University Hospital, 
      Freiburg D-79106, Germany.
LA  - eng
PT  - Journal Article
DEP - 20150428
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Carrier Proteins)
RN  - 0 (GABA Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a12 protein, mouse)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 146313-33-9 (betaine plasma membrane transport proteins)
RN  - 3SCV180C9W (Betaine)
RN  - EC 2.1.1.5 (BHMT protein, human)
RN  - EC 2.1.1.5 (Betaine-Homocysteine S-Methyltransferase)
RN  - EC 2.1.1.5 (Bhmt protein, mouse)
RN  - EC 2.1.1.5 (Bhmt protein, rat)
SB  - IM
MH  - Animals
MH  - Betaine/*blood
MH  - Betaine-Homocysteine S-Methyltransferase/genetics/metabolism
MH  - Carrier Proteins/genetics/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - GABA Plasma Membrane Transport Proteins/genetics/metabolism
MH  - Homocysteine/*blood/genetics
MH  - Homocystinuria/*blood/genetics
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Rats
MH  - Rats, Wistar
PMC - PMC4613678
OTO - NOTNLM
OT  - S-adenosyl-methionine
OT  - betaine
OT  - cystathionine-beta-synthase deficiency
OT  - hyperhomocysteinaemia
EDAT- 2015/07/17 06:00
MHDA- 2016/04/12 06:00
PMCR- 2015/08/01
CRDT- 2015/07/17 06:00
PHST- 2015/04/13 00:00 [received]
PHST- 2015/04/17 00:00 [accepted]
PHST- 2015/07/17 06:00 [entrez]
PHST- 2015/07/17 06:00 [pubmed]
PHST- 2016/04/12 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - BSR20150094 [pii]
AID - e00222 [pii]
AID - 10.1042/BSR20150094 [doi]
PST - epublish
SO  - Biosci Rep. 2015 Apr 28;35(4):e00222. doi: 10.1042/BSR20150094.