title: Increased affinity of choline acetyltransferase for choline in Alzheimer's disease: a steady-state kinetic study.
abstract: The steady-state kinetics of choline acetyltransferase (CAT) from autopsy samples of human caudate nucleus of aged controls and of patients with Alzheimer's disease was studied. In 10 samples from Alzheimer's disease-afflicted brains the affinity for the limiting substrate choline (Ch) was significantly higher: Michaelis constant KmCh was for these samples 1.93 +/- 0.72 mM while in the samples from 9 age-matched controls KmCh was 2.53 +/- 0.78 mM. The difference is statistically significant (P less than 0.05). Endogenous choline concentrations in the samples were 124 +/- 39 (n = 10) nmol/g wet wt. in the Alzheimer's disease-afflicted samples and 180 +/- 57 (n = 9) nmol/g wet weight (n = 9) in the control samples (P less than 0.05). The initial velocity at 70 microM acetyl co-enzyme (AcCoA) in Alzheimer's samples was 171.5 +/- 131.0 pmol [14C]acetyl choline [14C]ACh/mg protein/min as compared to the controls 422.1 +/- 231.0 pmol [14C]ACh/mg protein/min replicating many previous findings about decline of CAT activity in Alzheimer's disease. However, in the same samples the affinity for the other substrate acetyl-CoA (AcCoA) was significantly lower for the Alzheimer patients, KmAcCoA = 61 +/- 40 microM, than for the age-matched control patients, KmAcCoA = 28 +/- 8 microns (P less than 0.01). The data suggest some compensation of the loss of enzyme molecules via changed affinity for the limiting substrate, Ch.
authors: Department of Biochemistry, Arrhenius Laboratory, University of Stockholm, Sweden.
authors: O
authors: O
authors: Nordström
authors: M
authors: M
authors: Eliaz
authors: T
authors: T
authors: Bartfai
authors: C G
authors: CG
authors: Gottfries
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D002421:Caudate Nucleus / Q000201:enzymology*; D002794:Choline / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male
chemical_list: D002795:Choline O-Acetyltransferase; D002794:Choline