Abstract
Summary: Phosphodiesterase activities were examined in the supernatant and pellet fractions of a 30,000 × g preparation of brain tissues from human fetuses and young adults. Differences in total activity and distribution of the high and low Km activity enzymes for adenosine and guanosinc 3‘,5’-monophosphate (cyclic AMP and cyclic GIMP, respectively) were found. The mature cortex had 10 times more activity than the fetal brain for cyclic AMP hydrolysis and 15–20 times more activity for cyclic GIMP hydrolysis. In the fetus, more activity for both nucleotides at both high and low concentrations is associated with the supernatant fraction. With maturity, a shift in localization of high Km activity for cyclic GMP and low Km activities for both nucleotides to the particulate fraction is observed.
Michaelis constants for both mature and immature brains are similar. The Km values for cyclic AMP are 10-4 and 10-5 M and 10-4 and 10-6 M for cyclic GMP. The Vmax values differed by a factor of 10 between the high Km and the low Km forms for each substrate.
Differences were observed betweeen the fetus and the adult when the hydrolysis of one nucleotide. in the presence of either nucleotide stimulated the hydrolysis of Low concentrations of either nucleotide was measured in the presence of varying amounts of the other nucleotide. Low concentrations of the other in the adult whereas, in the fetus, low concentrations of cyclic AMP inhibited cyclic GMP hydrolysis At higher concentrations of either nucleotide, the addition of the other over a wide range of concentrations resulted in inhibition which was exaggerated in fetus.
Speculations: Differences in responsiveness to modulators observed between fetal and adult enzymes suggest the possiblity that these enzymes occur as isozymes. Substantiation of this possibility will require the separation of these enzymes in pure form.
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Rang, E. Cyclic Nucleotide Phosphodiesterase Activities of the Fetal and Mature Human Cerebral Cortex. Pediatr Res 11, 655–663 (1977). https://doi.org/10.1203/00006450-197705000-00007
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DOI: https://doi.org/10.1203/00006450-197705000-00007