title: Erythrocyte membrane acetylcholinesterase activity in subjects with MTHFR 677C-->T genotype.
abstract: BACKGROUND
  Increased homocysteine (Hcy) blood levels are correlated with vascular and neurological problems.
  
  
  OBJECTIVE
  The aim of the present study was to investigate erythrocyte membrane acetylcholinesterase (AChE) activity in subjects with the MTHFR C677T genotype in relation to Hcy.
  
  
  METHODS
  Blood was obtained from 22 individuals with the MTHFR C677T genotype before and after folic acid supplementation and once from controls (n = 30). Plasma folate, vitamin B(12) and total antioxidant status (TAS) were measured with commercial kits, Hcy by a HPLC method and membrane enzyme activity spectrophotometrically.
  
  
  RESULTS
  In MTHFR C677T carriers, AChE activity was significantly higher (4.20 +/- 0.12 x mg protein) and decreased to normal levels (3.14 +/- 0.10 x mg protein; p < 0.001) after therapy. TAS differed slightly before and after treatment. Hcy levels were significantly higher before (22.4 +/- 2.8 microM) compared to after (12.1 +/- 2.0 microM; p < 0.001) therapy and compared to controls (10.5 +/- 2.5 micromol/L; p < 0.001). In an in vitro study, incubation of Hcy-activated membrane AChE from controls with phenylalanine resulted in restoration of activity, but failed to reverse the stimulated enzyme from hyperhomocysteinaemic MTHFR C677T subjects before therapy. Alanine incubation protected the enzyme from Hcy activation in controls.
  
  
  CONCLUSIONS
  Increased membrane AChE activity may be due to high Hcy levels. In vitro, phenylalanine reversed the Hcy activation of the membrane enzyme from controls and alanine protected it from Hcy action.
authors.affiliation: Department of Experimental Physiology, Medical School, University of Athens, Greece. stsakir@cc.uoa.gr
authors.forename: Stylianos
authors.initials: S
authors.lastname: Tsakiris
authors.forename: Kleopatra H
authors.initials: KH
authors.lastname: Schulpis
authors.forename: Evangelos D
authors.initials: ED
authors.lastname: Papaconstantinou
authors.forename: Theodore
authors.initials: T
authors.lastname: Tsakiris
authors.forename: Ioanna
authors.initials: I
authors.lastname: Tjamouranis
authors.forename: Aglaia
authors.initials: A
authors.lastname: Giannoulia-Karantana
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000328:Adult; D000409:Alanine / Q000494:pharmacology; D003562:Cytidine / Q000235:genetics*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology*; D005492:Folic Acid / Q000627:therapeutic use; D005838:Genotype; D006710:Homocysteine / Q000494:pharmacology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy / Q000201:enzymology; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D010649:Phenylalanine / Q000494:pharmacology
chemical_list: D006710:Homocysteine; D010649:Phenylalanine; D003562:Cytidine; D005492:Folic Acid; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D000110:Acetylcholinesterase; D000409:Alanine