REGULATION OF NEONATAL GLUCONEOGENESIS: PHOSPHOENOL- PYRUVATE CARBOXYXINASE (GTP)-FERROACTIVATOR DEVELOPMENT AND DISTRIBUTION IN THE GUINEA PIG

Abstract

The key gluconeogenie enzyme, phosphoenolpyruvate carboxy-kinase (GTP) [PEPCK], is subject to hormonal regulation by a mechanism involving enzyme synthetic and/or degradative rates. PEPCK activity can also be affected by ions. Fe²⁺ has been shown to be involved in the activation of the enzyme in vivo. A protein necessary for the activation of purified PEPCK by Fe²⁺ has been identified in guinea pig tissue. Distribution of this PEPCK-Ferroactivator parallels that of the enzyme, being highest in liver [8550±1640 units/gm (M±SD), n = 6] to no activity in adipose tissue. 96% of PEPCK-Ferroactivator is found in cytosol and 4% in the mitochondria although cytosolic PEPCK activity is 43% and mitochondrial PEPCK is 57% of the total liver cell activity. Study of the development of PEPCK-Ferroactivator in fetal guinea pig liver reveals low levels (15% of adult) by the 40th day of gestation with an increase in activity to term when neonatal and maternal levels are equal. The maternal to fetal ratio of liver ferroactivator (units/gm) correlates with gestational age (r = 0.84, n = 15) in a linear regression y = 13.43 - 0.18x. Increase in cytosolic PEPCK activity and hence gluconeogenesis occurs rapidly postpartum by a mechanism not yet completely elucidated. The existance of PEPCK-Ferroactivator activity which is involved in the rapid activation of PEPCK by Fe²⁺ in neonatal liver suggests that Fe²⁺ activation may be important in regulating neonatal gluconeogenesis.

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