Homocysteine inhibits butyrylcholinesterase activity in rat serum.

In the present work we investigated the in vitro effects of homocysteine (Hcy) and methionine (Met), metabolites accumulated in homocystinuria, on butyrylcholinesterase (BuChE) activity in rat serum. We also studied the kinetics of the inhibition of BuChE activity caused by Hcy. For determination of BuChE we used serum of 60-day-old Wistar rats, which was incubated in the absence (control) or presence of Hcy (0.01-0.5 mM) or Met (0.2-2.0 mM). The kinetics of the interaction of Hcy and BuChE was determined using the Lineweaver-Burk double reciprocal plot. Results showed that serum BuChE activity was not altered by Met, but it was significantly inhibited (37%) by 500 microM Hcy, a concentration similar to those found in blood of homocystinuric patients. The apparent Km values, in the absence and presence of 500 microM of Hcy, were 0.034 and 0.142 mM, respectively, and V(max) of BuChE for acetylcholine (ACh) as substrate was 1.25 micromol ACSCh/h/mg of protein. The Ki value obtained was 120 microM, and the inhibition was of the competitive type, suggesting a common binding site for Hcy and ACh. It is proposed that inhibition of cholinesterase activity may be one of the mechanisms involved in the neurological dysfunction observed in homocystinuria.