Postnatal development of peroxisomal and mitochondrial enzymes in rat liver

Abstract

Subcellular organellles from livers of rats three days prenatal to 50 weeks postnatal were separated on sucrose gradients. The peroxisomes had a constant density of 1.243 g/ml throughout the life of the animal. The density of the mitochondria changed from about 1.236 g/ml at birth to a constant value of 1.200 g/ml after two weeks. The peroxisomal and mitochondrial fatty acid beta-oxidation and the peroxisomal and supernatant activities of catalase and glycerol-3-phosphate dehydrogenase were measured at each age, as well as the peroxisomal core enzyme, urate oxidase, and the mitochondrial matrix enzyme, glutamate dehydrogenase. All of these activities were very low or undetectable before birth. Mitochondrial glutamate dehydrogenase and peroxisomal urate oxidase reached maximal activities per g of liver at two and five weeks of age, respectively. Fatty acid beta-oxidation in both peroxisomes and mitochondria and peroxisomal glycerol-3-phosphate dehydrogenase exhibited maximum activities per g of liver between one and two weeks of age before weaning and then decreased to steady state levels in the adult. Peroxisomal beta-oxidation accounted for at least 10% of the total beta-oxidation activity in the young rat liver, but became 30% of the total in the liver of the adult female and 20% in the adult male due to a decrease in mitochondrial beta-oxidation after two weeks of age. The greatest change in beta-oxidation was in the mitochondrial fraction rather than in the peroxisomes. At two weeks of age, four times as much beta-oxidation activity was in the mitochondria as in the peroxisomal fraction. Peroxisomal glycerol-3-phosphate dehydrogenase activity accounted for 5% to 7% of the total activity in animals younger than one week, but only 1% to 2% in animals older than one week. Up to three weeks of age, 85% to 90% of the liver catalase was recovered in the peroxisomes. The activity of peroxisomal catalase per g of rat liver remained constant after three weeks of age, but the total activity of catalase further increased 2.5- to 3-fold, and all of the increased activity was in the supernatant fraction.

Fatty acid oxidation and ketogenesis during development

“…The experimental evidence presently available indicates that peroxisomal !3-oxidation plays a minor role in overall fatty acid oxidation in both adult (Debeer and Mannaerts, 1983) and newborn (Krahling et al, 1979 ;Horie, Ishii and Suga, 1981) Lockwood, 1973 ;Warshaw, 1979 ;Williamson, 1982).…”

Metabolic development in the liver and the implications of the n-3 fatty acid supply

“…Metabolic adaptation of energy substrate processing with a shift in hepatic glycolysis and fatty acid oxidation occurs following birth (14) and is likely important to the maintenance of blood glucose, avoidance of excess hepatic fatty acid accumulation, and efficient utilization of amino acids for protein and peptide synthesis. Early studies showed that the activity and expression of hepatic mitochondrial and peroxisomal enzymes of fatty acid oxidation are low in the fetus and increase rapidly after birth, consistent with the onset of feeding with the high-fat milk diet (27,44). The n-6 and n-3 fatty acids contribute to regulation of fatty acid synthesis and oxidation in adult liver, with the n-3 fatty acids having unique effects that suppress hepatic triglyceride synthesis and secretion (22,37,39,40,50).…”

Carnitine Acetyltransferase in Developing Mammals

“…Figure 3 shows that in the liver there is a steep rise in the specific activity at the time of weaning as described by others (9). In contrast, in brown adipose tissue where peroxi somes have been described to be present using histological techniques (19), activity increases to a peak on day 6 and then decreases again.…”

“…Using a sucrose density gradient as described by Markwell (13), succinic dehydrogenase and catalase activities could never be properly separated from each other and this has since been found by others working with neonatal rat liver (9).…”