Cerebellar alpha-ketoglutarate dehydrogenase activity is reduced in spinocerebellar ataxia type 1.
We measured the activity of the thiamine pyrophosphate-dependent enzyme alpha-ketoglutarate dehydrogenase complex in postmortem brain of 12 patients with the spinocerebellar ataxia type 1 form of olivopontocerebellar atrophy. alpha-Ketoglutarate dehydrogenase complex activity measured in the absence of thiamine pyrophosphate was markedly reduced (-72%) in olivopontocerebellar atrophy cerebellar cortex. Decreased activity of this key rate-limiting Krebs cycle enzyme could compromise cerebellar energy metabolism and excitatory amino acid synthesis and thereby contribute to the brain dysfunction of olivopontocerebellar atrophy.
Mastrogiacomo
F
F
Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Kish
S J
SJ
D000328:Adult; D001224:Aspartic Acid / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology; D004734:Energy Metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006801:Humans; D007655:Ketoglutarate Dehydrogenase Complex / Q000172:deficiency / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D012016:Reference Values; D013132:Spinocerebellar Degenerations / Q000201:enzymology*
D005971:Glutamates; D018377:Neurotransmitter Agents; D001224:Aspartic Acid; D018698:Glutamic Acid; D007655:Ketoglutarate Dehydrogenase Complex