Regulation of hepatic gluconeogenesis by rapid compartmentation of mitochondrial adenine nucleotides in the newborn rabbit.

In newborn rabbit liver the mitochondrial adenine nucleotide pool (ATP + ADP + AMP) size increased from 6.4 +/- 0.4 to 14.5 +/- 0.7 nmol/mg mitochondrial protein within 2 hr after birth. Gluconeogenesis (from lactate) in isolated hepatocytes rose from 13.1 +/- 1.9 at birth to 42.3 +/- 2.4 nmol glucose/min/10(7) cells at 2 hr. Pyruvate carboxylation in isolated mitochondria increased in parallel from 42.8 +/- 4.9 at birth to 108.6 +/- 8.2 nmol H14CO-3/min/mg mitochondrial protein at 2 hr. The similar developmental time course for these three phenomena suggested that the rapid increase in gluconeogenesis might be a result of increased availability of adenine nucleotides to the ATP-requiring mitochondrial enzyme, pyruvate carboxylase. Manipulation of the mitochondrial adenine nucleotide pool size in vitro resulted in predictable changes in the rate of pyruvate carboxylation. We concluded that the postnatal increase in mitochondrial adenine nucleotide content stimulates pyruvate carboxylation, thereby causing a rapid increase in the rate of gluconeogenesis.