Inhibition of human plasma cholinesterase by malachite green and related triarylmethane dyes: Mechanistic implications

KUCUKKILINC T., Ozer I.

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, cilt.440, sa.2, ss.118-122, 2005 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 440 Sayı: 2
  • Basım Tarihi: 2005
  • Doi Numarası: 10.1016/j.abb.2005.06.003
  • Dergi Adı: ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.118-122
  • Anahtar Kelimeler: plasma cholinesterase, enzyme inhibition, pararosaniline, malachite green, methyl green, triarylmethane dyes, AMINO-ACID-RESIDUES, ACTIVE-SITE GORGE, HUMAN BUTYRYLCHOLINESTERASE, ALZHEIMERS-DISEASE, HUMAN ACETYLCHOLINESTERASE, E2020 ARICEPT(R), BINDING, TRIPHENYLMETHANE, METABOLISM, PROTEINS
  • Hacettepe Üniversitesi Adresli: Evet

Özet

The inhibitory effects of the cationic triarylmethane (TAM(+)) dyes, pararosaniline (PR+), malachite green (MG(+)), and methyl green (MeG(+)) on human plasma cholinesterase (BChE) were studied at 25 degrees C in 100 mM Mops, pH 8.0, with butyrylthiocholine as substrate. PR+ and MG' caused linear mixed inhibition of enzyme activity. The respective inhibitory parameters were K-i = 1.9 +/- 0.23 mu M, alpha = 13 +/- 48, beta = 0 and K-i = 0.28 +/- 0.037 mu M, alpha = 23 +/- 7.4, beta = 0. MeG(+) acted as a competitive inhibitor with Ki = 0.12 +/- 0.017 mu M (alpha, infinity, beta, not applicable). The Ki values were within the same range reported for a number of ChE inhibitors including propidium ion, donepezil, and the phenothiazines, suggesting that TAM(+)s are active site ligands. On the other hand, the alpha values failed to correlate with values previously reported for a number of ChE inhibitors. It appears that mixed inhibition is the combined result of more than one type of binding and S-I interference. The impact of ligands at the choline-specific and peripheral anionic sites (or, possibly, accessory structural domains) on BChE activity needs to be studied in further detail. (c) 2005 Elsevier Inc. All rights reserved.