Physiological implications of the alteration of 6-phosphofructo-1-kinase isozyme pools during brain development and aging.
The 6-phosphofructo-1-kinase (PFK) isozyme pools from brains of fetal, neonatal, young adult (3 months) and aged (30 months) rats were studied using chromatographic and immunological techniques. Also, the changing subunit composition of each isozyme pool was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis on 6% slab gels and by immunoblotting with subunit-specific antibodies. The total PFK activity increased over seven-fold during the 30 days following birth, and the L-type, M-type, and C-type subunits increased approximately 2-fold, 7-fold, and 24-fold, respectively. In the near-term fetal brain and early neonatal brain, the L-type and M-type subunits were the predominant forms and were present in approximately equal amounts. During the second second week of postnatal brain maturation, the levels of the M-type and C-type subunit began to significantly increase. Consequently, during postnatal development, the isozyme pools switched from L-M-rich forms to M-C-rich forms. In aged brain relative to the young adult (3 months) brain, the 20% loss of total activity was associated with 27% and 18% losses of the M-type and C-type subunits, respectively. Examination of the regulatory properties of the various PFK isozyme pools revealed that at the low concentration of fructose-6-P and high level of ATP which are thought to occur in vivo, fructose-2,6-P2 was required for measurable PFK activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Dunaway
G A
GA
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62708.
Kasten
T P
TP
D000375:Aging; D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology / Q000254:growth & development*; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D007527:Isoenzymes; D046911:Macromolecular Substances; D010732:Phosphofructokinase-1