Developmental changes in the activity of enzymes of purine metabolism in rat neuronal cells in culture and in whole brain.
The activities (Vmax) of several enzymes of purine nucleotide metabolism were assayed in premature and mature primary rat neuronal cultures and in whole rat brains. In the neuronal cultures, representing 90% pure neurons, maturation (up to 14 days in culture) resulted in an increase in the activities of guanine deaminase (guanase), purine-nucleoside phosphorylase (PNP), IMP 5'-nucleotidase, adenine phosphoribosyltransferase (APRT), and AMP deaminase, but in no change in the activities of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenosine deaminase, adenosine kinase, and AMP 5'-nucleotidase. In whole brains in vivo, maturation (from 18 days of gestation to 14 days post partum) was associated with an increase in the activities of guanase, PNP, IMP 5'-nucleotidase, AMP deaminase, and HGPRT, a decrease in the activities of adenosine deaminase and IMP dehydrogenase, and no change in the activities of APRT, AMP 5'-nucleotidase, and adenosine kinase. The profound changes in purine metabolism, which occur with maturation of the neuronal cells in primary cultures in vitro and in whole brains in vivo, create an advantage for AMP degradation by deamination, rather than by dephosphorylation, and for guanine degradation to xanthine over its reutilization for synthesis of GMP. The physiological meaning of the maturational increase in these two ammonia-producing enzymes in the brain is not yet clear. The striking similarity in the alterations of enzyme activities in the two systems indicates that the primary culture system may serve as an appropriate model for the study of purine metabolism in brain.
Brosh
S
S
Department of Clinical Biochemistry, Beilinson Medical Center, Petah Tikva, Israel.
Sperling
O
O
Bromberg
Y
Y
Sidi
Y
Y
D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development; D006147:Guanine / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D011687:Purines / Q000378:metabolism*; D051381:Rats / Q000196:embryology
D011687:Purines; D000249:Adenosine Monophosphate; D006147:Guanine