Perinatal Regulation of Mitochondrial and Cytoplasmic Enzymes in Rabbit Liver

Abstract

The control of postnatal development of the activities of cytoplasmic and mitochondrial malate dehydrogenases and of the purely mitochondrial enzyme, cytochrome oxidase, has been studied in rabbit liver. Each of the three enzymes increased 1.6-1.8-fold in activity during the first 2 days of life. Delivery of animals at varying stages of maturation demonstrated (table II) that the increase in all cases occurred when delivery was effected and was a result of some aspect of the process of birth itself.Maturation affects cytoplasmic malate dehydrogenase (MDH) differently than the two mitochondrial enzymes. Cytoplasmic MDH is relatively constant in activity in utero and increases approximately 80% whenever delivery is effected (table II, figure 1). In contrast, both the mitochondrial enzymes decrease 40 % in activity if animals remain in utero beyond normal term. Their increase (20-40%) following premature delivery is considerably smaller than the large (1.5-fold) increase following postmature delivery.Using the artificial feeding procedure developed for this study, newborn animals were maintained for 48 h in an hypoxic environment. Preliminary results suggested that development of enzyme activity was affected by hypoxia. Speculation

A Convenient Neonatal Model for Developmental Studies Requiring Artificial Diets

“…the piglet (7), rat (2,8), and rabbit (3,9). Smith (3,10) has used the artificially fed neonatal rabbit to study the development of enzymes, but most studies have been aimed at relating diet to growth and body composition (2,7,11). The model we have established using the rabbit pup is advantageous over those previously reported for several reasons.…”

Developmental regulation and cellular distribution of human cytosolic malate dehydrogenase (MDH1)

“…A rapid transition toward fatty acid b-oxidation through the increasing activity of carnitine palmitoyl transferase 1 (CPT-1) is found in rat heart during the early postnatal period [Warshaw, 1972]. Correspondingly, it has been reported that MDH1 and MDH2 increased twofold until birth in developing rabbit liver and then declined after birth [Smith, 1970]. This reflects that the increased expression of MDHs is required for the high demands of energy metabolism in developing tissues [Ding et al, 1994].…”

Postnatal Changes in Pyridine Nucleotides in Rat Hepatocytes: Composition and O2 Dependence

“…The similarities in Oz requirements for oxidation of pyridine nucleotides and mitochondrial cytochromes at different ages (Fig. 3) suggest that the development of mitochondrial substrate oxidation occurs in concert with that of mitochondrial respiratory apparatus even though there appears to be a lack of synchronization of the appearance of many enzyme and cytochrome systems in late fetal and early postnatal mitochondria (1)(2)(3)(4)(5). The remarkable postnatal changes in oxidative and reductive status of the pyridine nucleotides and the low 0 2 requirements for oxidation in neonatal cells suggest that these less differentiated cells have a unique metabolic demand for reducing equivalents that differs from that of adult tissues.…”

“…(Pediatr Res 30: 11 2-1 17, 1991) Abbreviations PS0, half-maximal associated greater demand for oxidizable substrates and reducing equivalents. In liver, the age-dependent increase in cellular respiration is attained by marked changes in the composition and contents of the enzymes of the respiratory systems (1)(2)(3)(4)(5) and by selective use of specific respiratory substrates (6, 7). We recently found that hepatocytes from newborn rats preferentially use succinate for cell respiration compared to a variety of other carbohydrate or amino acid substrates (6,7).…”