Neonatal hypoxia or maternal diabetes delays postnatal development of liver mitochondria.
The matrix adenine nucleotide pool size of rat liver mitochondria was low at birth (2.6-3.0 nmol ATP + ADP + AMP/mg mitochondrial protein). After parturition, the pool size was increased by 50-75% within 1 h, which was sufficient for full development of state 3 respiration rates. The adenine nucleotide pool size continued to increase to 100-150% of the value at birth by 2-3 h postnatal. The ATP/ADP ratio in isolated mitochondria also increased postnatally, to about double the value at birth by 3 h. There were no matrix volume changes over this postnatal period, so the increased ATP + ADP + AMP pool size and the increased ATP/ADP ratio together inferred an overall increase of about 5-fold in the matrix ATP concentration under aerobic conditions. The postnatal uptake of adenine nucleotides into mitochondria occurred at a slower rate in newborns that were hypoxic (11% 02) and in newborns of diabetic mothers (diabetes induced on day 5 of gestation by streptozotocin injection). The normal increase in matrix ATP content is responsible for the rapid stimulation of pyruvate carboxylation (an ATP-requiring matrix reaction) and this in turn contributes to the rapid postnatal onset of gluconeogenesis. The results suggest that delayed adenine nucleotide uptake into liver mitochondria may retard initiation of gluconeogenesis in newborns experiencing hypoxia, as in respiratory distress or in newborns of diabetic mothers. We speculate that this mechanism contributes to the persistent hypoglycemia that is typical of these at-risk newborns.
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000033:anatomy & histology / Q000254:growth & development*; D005260:Female; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000254:growth & development / Q000473:pathology*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D010101:Oxygen Consumption; D049590:Postpartum Period; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides