Regional difference in the kinetics of choline acetyltransferase in brains of neurologically normal elderly people and those with Alzheimer-type dementia.
In order to clarify the biochemical changes which occur in the brains of patients suffering from Alzheimer-type dementia (ATD), the kinetics of choline acetyltransferase (ChAT) were measured in 8 or 11 regions of post-mortem brains of 6 patients with non-neurological diseases (control subjects) and 8 patients with ATD. In the control subjects, Michaelis constants (Km) of ChAT for choline were lower in the caudate nucleus and putamen than in other regions examined, whereas Km values for acetyl-CoA in these two regions were higher. Maximal velocities (Vmax) for the control subjects were higher in the caudate nucleus and putamen than in the other regions studied. Km values for choline of ATD patients were higher than those of control subjects in all regions except the amygdala and substantia innominata (innominate); however, Km values for acetyl-CoA of ATD patients were higher than those of control subjects only in the caudate nucleus, putamen and thalamus. Vmax values of ATD patients were lower than those of control subjects in all the regions of brains with ATD. These results suggest that the binding site of ChAT for choline is sensitive to the pathological process of ATD, whereas the binding site for acetyl-CoA is resistant. Based on the presence or absence of variations of Km values, we have classified brain regions into 3 types: highly sensitive, somewhat sensitive or resistant to the pathological process of ATD.
Koshimura
K
K
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Nakamura
S
S
Miwa
S
S
Fujiwara
M
M
Kameyama
M
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D001921:Brain / Q000201:enzymology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male
D002795:Choline O-Acetyltransferase