title: The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion.
abstract: OBJECTIVE
  The enzyme catechol-O-methyltransferase (COMT) plays a primary role in the metabolism of catecholamine neurotransmitters and is implicated in the modulation of cognitive and emotional responses. The best characterized single nucleotide polymorphism (SNP) of the COMT gene consists of a valine (Val)-to-methionine (Met) substitution at codon 108/158. The Met-containing variant confers a marked reduction in COMT catalytic activity. We recently showed that the activity of recombinant COMT is positively regulated by the enzyme Met sulphoxide reductase (MSR), which counters the oxidation of Met residues of proteins. The current study was designed to assess whether brain COMT activity may be correlated to MSR in an allele-dependent fashion.
  
  
  METHODS
  COMT and MSR activities were measured from post-mortem samples of prefrontal cortices, striata and cerebella of 32 subjects by using catechol and dabsyl-Met sulphoxide as substrates, respectively. Allelic discrimination of COMT Val(108/185) Met SNP was performed using the Taqman 5'nuclease assay.
  
  
  RESULTS
  Our studies revealed that, in homozygous carriers of Met, but not Val alleles, the activity of COMT and MSR was significantly correlated throughout all tested brain regions.
  
  
  CONCLUSIONS
  These results suggest that the reduced enzymatic activity of Met-containing COMT may be secondary to Met sulphoxidation and point to MSR as a key molecular determinant for the modulation of COMT activity.
authors: Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, USA.
authors: Jackob
authors: J
authors: Moskovitz
authors: Department of Psychiatry and Behavioral Science, School of Medicine, University of Texas Health Science Center, Houston, USA.
authors: Consuelo
authors: C
authors: Walss-Bass
authors: Southwest Brain Bank, Department of Psychiatry, School of Medicine, University of Texas Health Science Center, San Antonio, USA.
authors: Dianne A
authors: DA
authors: Cruz
authors: Southwest Brain Bank, Department of Psychiatry, School of Medicine, University of Texas Health Science Center, San Antonio, USA.
authors: Peter M
authors: PM
authors: Thompson
authors: Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, USA.
authors: Jenaqua
authors: J
authors: Hairston
authors: Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, USA.
authors: Marco
authors: M
authors: Bortolato
mesh_terms: D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000201:enzymology / Q000235:genetics; D001921:Brain / Q000201:enzymology*; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D051150:Methionine Sulfoxide Reductases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics
chemical_list: D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D002394:Catechol O-Methyltransferase
keywords: Met oxidation; catechol-O-methyltransferase; gene polymorphism; oxidative stress; post-mortem human brain
references: Am J Psychiatry. 1997 Jan;154(1):113-5
references: 8988970
references: Mol Psychiatry. 1998 Jul;3(4):342-5
references: 9702744
references: Thorax. 2000 Jul;55(7):574-8
references: 10856317
references: Pharmacol Rev. 1999 Dec;51(4):593-628
references: 10581325
references: J Affect Disord. 2010 Sep;125(1-3):341-4
references: 20122740
references: Biol Psychiatry. 1997 Aug 15;42(4):282-5
references: 9270905
references: J Neurosci. 2005 May 18;25(20):5038-45
references: 15901785
references: Front Behav Neurosci. 2014 Mar 06;8:71
references: 24639636
references: Psychiatry Res. 2004 Jun 30;127(1-2):121-36
references: 15261711
references: Psychiatry Res. 1997 Mar 24;69(2-3):71-7
references: 9109174
references: Lancet. 1981 May 16;1(8229):1102
references: 6112467
references: Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6917-22
references: 11381111
references: J Affect Disord. 2013 Sep 5;150(2):499-506
references: 23769608
references: J Affect Disord. 2011 Jul;132(1-2):293-6
references: 21397335
references: Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14071-5
references: 9826655
references: J Psychiatry Neurosci. 2005 May;30(3):178-86
references: 15944742
references: Curr Top Dev Biol. 2008;80:93-133
references: 17950373
references: BMJ. 1998 Apr 18;316(7139):1236-8
references: 9553006
references: Neurosci Lett. 2006 Jan 30;393(2-3):170-3
references: 16233957
references: J Neurochem. 1983 Jan;40(1):215-9
references: 6848660
references: Psychiatr Genet. 1997 Spring;7(1):13-7
references: 9264133
references: Biol Psychiatry. 1998 Mar 15;43(6):425-31
references: 9532347
references: Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1416-20
references: 1847521
references: Am J Med Genet B Neuropsychiatr Genet. 2009 Mar 5;150B(2):219-25
references: 18506707
references: Neuropsychopharmacology. 2003 Aug;28(8):1521-30
references: 12799619
references: Rev Bras Psiquiatr. 2008 Sep;30(3):281-9
references: 18833430
references: Am J Psychiatry. 1996 Feb;153(2):268-70
references: 8561211
references: J Neurochem. 1984 Mar;42(3):826-32
references: 6693904
references: J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57
references: 9881538
references: Comp Biochem Physiol A Mol Integr Physiol. 2012 Apr;161(4):406-14
references: 22230185
references: Am J Hum Genet. 2004 Nov;75(5):807-21
references: 15457404
references: Am J Med Genet B Neuropsychiatr Genet. 2003 Jul 1;120B(1):29-34
references: 12815735
references: Rev Physiol Biochem Pharmacol. 1992;120:1-29
references: 1519017
references: Am J Hum Genet. 2003 Jul;73(1):152-61
references: 12802784
references: Psychol Med. 2011 Apr;41(4):779-88
references: 20667170
references: J Biol Chem. 1958 Sep;233(3):702-5
references: 13575440
references: J Biol Chem. 2004 May 28;279(22):23710-8
references: 15031283
references: Biol Psychiatry. 1999 Aug 15;46(4):557-67
references: 10459407
references: Br J Psychiatry. 2001 Oct;179:351-5
references: 11581117
references: Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1776-80
references: 8700834
references: Biol Psychiatry. 2002 Oct 1;52(7):701-7
references: 12372660
references: Neuropsychopharmacology. 1999 Jul;21(1):63-8
references: 10379520
references: Transl Psychiatry. 2013;3:e214
references: 23321811
references: Int Rev Neurobiol. 2010;95:29-47
references: 21095458
references: Biol Psychiatry. 2006 Jul 15;60(2):141-51
references: 16476412
references: FEBS Lett. 1999 Jul 30;456(1):17-21
references: 10452521
references: Exp Brain Res. 2007 Jul;180(4):765-74
references: 17333008
references: Am J Psychiatry. 1985 Sep;142(9):1067-9
references: 4025624
references: Int J Neuropsychopharmacol. 2014 Oct;17(10):1707-13
references: 24735585
references: Eur J Biochem. 1997 Jan 15;243(1-2):452-9
references: 9030772
references: Am J Med Genet. 1996 Nov 22;67(6):515-22
references: 8950408
references: Indian J Psychol Med. 2014 Jul;36(3):338-40
references: 25035567
references: Biol Psychiatry. 2003 Jul 1;54(1):40-8
references: 12842307
references: Pharmacogenetics. 1996 Jun;6(3):243-50
references: 8807664
references: Biochim Biophys Acta. 2005 Jan 17;1703(2):213-9
references: 15680229
references: Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):12920-5
references: 11606777
references: Biochemistry. 1995 Apr 4;34(13):4202-10
references: 7703232
references: Am J Psychiatry. 1983 Oct;140(10):1322-6
references: 6624962
references: Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15036-40
references: 8986759
references: J Am Geriatr Soc. 2012 Mar;60(3):588-9
references: 22409736
references: J Biol Chem. 2007 Oct 19;282(42):31094-102
references: 17724020
references: J Neurosci. 2005 Jan 26;25(4):836-42
references: 15673663
references: Schizophr Res. 1991 Mar-Apr;4(2):173-91
references: 2039760
references: Neuropsychopharmacology. 2007 Jan;32(1):162-70
references: 16823382
references: DNA Cell Biol. 1991 Apr;10(3):181-9
references: 1707278
references: Eur J Biochem. 1994 Aug 1;223(3):1049-59
references: 8055944
references: Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):2969-74
references: 9096330
references: World Psychiatry. 2003 Oct;2(3):136-46
references: 16946919
references: Arch Gen Psychiatry. 2003 Sep;60(9):889-96
references: 12963670
references: Am J Psychiatry. 1987 Apr;144(4):465-7
references: 3565615
references: J Am Acad Child Adolesc Psychiatry. 2010 Aug;49(8):841-9
references: 20643317
references: Am J Psychiatry. 2002 Apr;159(4):652-4
references: 11925305
references: Biol Psychiatry. 1996 Oct 15;40(8):726-30
references: 8894064