Kasten T P, Mhaskar Y, Dunaway G A
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62794-9230.
Mol Cell Biochem. 1993 Mar 10;120(1):61-8. doi: 10.1007/BF00925985.
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.
测定了3个月、12个月和25个月大的大鼠大脑皮层、中脑、脑桥延髓和小脑中6-磷酸果糖-1-激酶（PFK）的总活性、每种PFK亚基的含量以及果糖-2,6-二磷酸（fructose-2,6-P2）的水平。此外，还研究了果糖-2,6-P2在调节脑PFK活性中的作用。通过2-脱氧-D-葡萄糖摄取测定的葡萄糖利用报告损失与每个区域的PFK活性之间存在正相关。也就是说，这两个参数在12个月大时降至最低水平，此后一直保持下降且相当稳定。果糖-2,6-P2水平似乎与葡萄糖利用的区域变化没有直接关联。此外，还发现了PFK亚基的区域特异性和年龄相关变化，尽管这些变化显然与葡萄糖利用减少无关。由于内源性水平较高，脑PFK显然被果糖-2,6-P2饱和，并且它含有很大比例的C型亚基，这会降低催化效率。因此，脑PFK可能以一种构象状态存在，使得它能够轻易地消耗果糖-6-磷酸，而不是处于需要激活的抑制状态。这可能部分解释了大脑在能量产生中有效但保守地利用可用葡萄糖的能力。
