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Regulation of brain 6-phosphofructo-1-kinase: effects of aging, fructose-2,6-bisphosphate, and regional subunit distribution

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Abstract

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.

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Abbreviations

fructose-2,6-P2 :

D-fructose 2,6-bisphosphate

fructose-6-P:

D-fructose 6-phosphate

PAGE:

Polyacrylamide Gel Electrophoresis

PFK:

6-phosphofructo-1-kinase

PPi-PFK:

Pyrophosphate-dependent Phosphofructokinase, ribose-1,5-P2, ribose-1,5-bisphosphate

SDS:

Sodium Dodecyl Sulfate

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Authors and Affiliations

  1. Department of Pharmacology, Southern Illinois University School of Medicine, P. O. Box 19230, 62794-9230, Springfield, IL, USA

    Thomas P. Kasten, Yashanad Mhaskar & George A. Dunaway

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  1. Thomas P. Kasten
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  2. Yashanad Mhaskar
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  3. George A. Dunaway
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Kasten, T.P., Mhaskar, Y. & Dunaway, G.A. Regulation of brain 6-phosphofructo-1-kinase: effects of aging, fructose-2,6-bisphosphate, and regional subunit distribution. Mol Cell Biochem 120, 61–68 (1993). https://doi.org/10.1007/BF00925985

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  • DOI: https://doi.org/10.1007/BF00925985

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