Immunoglobulins from patients with amyotrophic lateral sclerosis affect human erythrocyte acetylcholinesterase.
Human erythrocyte acetylcholinesterase (AChE) solubilized with Triton X-100 and obtained as a complex with micelles containing Triton and membrane phospholipids was incubated with immunoglobulins (Igs) from patients with amyotrophic lateral sclerosis (ALS) and from normal individuals. The temperature dependence of the AChE activity was determined. Biphasic (broken) Arrhenius plots were obtained with control Igs with the break point at 32.8 +/- 0.3 degrees C (SD, n = 18) indicating that the enzyme changes its conformation at this temperature. With ALS-Igs monophasic (linear) plots were observed in 14 cases and a biphasic in one case. ALS-Igs prevent the conformational change occurring at the break point temperature. The activation energy at physiological temperature increased by 60% from 2.4 to 3.8 kcal/mol (10.0-15.9 kJ/mol) which implies that ALS-Igs inhibit AChE. Thus, ALS-patients have autoantibodies that change the normal behaviour of erythrocyte AChE and which bind to the enzyme molecule or/and to phospholipids associated with the enzyme. At least part of the autoantibodies should be directed against the enzyme molecule, since a change in the Arrhenius plot was also observed in a control experiment with AChE which probably had micelles without any phospholipids. This enzyme was isolated by affinity chromatography and was washed with a buffer containing Triton X-100 before desorption from the affinity column, a treatment known to remove all phospholipids from erythrocyte AChE.
Sindhuphak
R
R
Institute of Biochemistry, Biomedical Center, Uppsala, Sweden.
Karlsson
E
E
Conradi
S
S
Ronnevi
L O
LO
D000110:Acetylcholinesterase / Q000097:blood* / Q000276:immunology; D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology*; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007136:Immunoglobulins / Q000302:isolation & purification / Q000502:physiology*; D008563:Membrane Lipids / Q000097:blood / Q000502:physiology; D008823:Micelles; D010743:Phospholipids / Q000097:blood / Q000502:physiology; D012016:Reference Values; D013816:Thermodynamics
D007136:Immunoglobulins; D008563:Membrane Lipids; D008823:Micelles; D010743:Phospholipids; D000110:Acetylcholinesterase