Regulation of brain 6-phosphofructo-1-kinase: effects of aging, fructose-2,6-bisphosphate, and regional subunit distribution.
Total 6-phosphofructo-1-kinase (PFK) activity, amounts of each type of PFK subunit, and levels of fructose-2,6-P2 in the cerebral cortex, midbrain, pons-medulla, and cerebellum of 3, 12, and 25 month rats were measured. Further, the role of fructose-2,6-P2 in the regulation of brain PFK activity was examined. A positive correlation was found to exist between the reported losses of glucose utilization as measured by 2-deoxy-D-glucose uptake and PFK activity in each region. That is, both parameters decreased to their lowest level by 12 months of age and remained decreased and fairly constant thereafter. Fructose-2,6-P2 levels did not appear to directly correlate with regional changes in glucose utilization. Also, region-specific and age-related alterations of the PFK subunits were found although these changes apparently did not correlate with decreased glucose utilization. Brain PFK is apparently saturated with fructose-2,6-P2 due to the high endogenous levels, and it contains a large proportion of the C-type subunit which dampens catalytic efficiency. Consequently, brain PFK could exist in a conformational state such that it can readily consume fructose-6-P rather than in an inhibited state requiring activation. This may explain, in part, the ability of brain to efficiently but conservatively utilize available glucose in energy production.
Kasten
T P
TP
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62794-9230.
Mhaskar
Y
Y
Dunaway
G A
GA
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D004734:Energy Metabolism; D005635:Fructosediphosphates / Q000378:metabolism*; D007700:Kinetics; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D005635:Fructosediphosphates; C027652:fructose 2,6-diphosphate; D010732:Phosphofructokinase-1