POSTNATAL ACCUMULATION OF ADENINE NUCLEOTIDES IN RABBIT LIVER MITOCHONDRIA AND THE DEVELOPMENT OF CITRULLINE SYNTHESIS

Abstract

Liver mitochondria (mito) accumulate adenine nucleotides right after birth thereby greatly increasing the matrix ATP+ADP+AMP content (BBA: 681:300, 1982). Bioenergetic function is also enhanced. Overall, there is a large increase in matrix ATP that might be expected to stimulate ATP-dependent pathways within the mito. Carbamyl phosphate synthetase and ornithine carbamyltransferase are enzymes of the urea cycle that are localized in the matrix; they catalyze citrulline (CIT) synthesis from ornithine, NH3, and CO2 in an ATP-dependent reaction sequence. We investigated whether the postnatal increase in the matrix ATP pool size affects CIT synthesis. Mito were isolated from rabbit pups at birth and at 2 hrs of age. ATP, ADP and AMP were determined enzymatically in PCA extracts. CIT synthesis (assayed by 14CO2 fixation) increased between birth and 2 hrs, from 1.38±.35 to 2.40± .26 umol/hr/mg mito protein. The matrix ATP+ADP+AMP pool size (nmol/mg mito protein) increased from 5.7±.8 at birth to 15.1±1.6 at 2 hrs and the matrix ATP/ADP ratio increased from 1.47 to 3.52. The larger adenine nucleotide pool size together with the higher ATP/ADP ratio resulted in a 3.4-fold increase in matrix ATP concentration. Two moles ATP are required per mole CIT, so the increase in ATP appears to account for the 1.8-fold increase in CIT synthesis. Conclusion: The accumulation of adenine nucleotides and the maturation of energetic functions within the first few hours after birth allow a rapid postnatal increase in the capacity for CIT synthesis. (NIH HD 16936)