Hepatic Metallothionein as a Source of Zinc and Cysteine during the First Year of Life

Abstract

ABSTRACT. Metallothionein, a high cysteine-containing protein, can bind with both essential and nonessential metals and thus play an important role as a metal storage protein and also in the detoxification of toxic metals. Although in the human fetus, levels of trace minerals and metallothionein are very high, their postnatal changes are not well documented. The purpose of the present investigation, therefore, was to quantify the accumulation of metallothionein in premature and full-term infants during the first year of life and to identify factors affecting its accumulation. From 47 postmortem samples, it was determined that hepatic metallothionein levels were highest in newborn premature and full-term infants falling to levels found in older children by 4.4 months of age. Hepatic zinc levels were also highest in the youngest infants, falling with increasing postnatal age. There was a significant positive correlation between zinc and metallothionein at all ages. However, there was a negative correlation between hepatic metallothionein levels and cystathionase activity. Hepatic copper and metallothionein levels were unrelated. The renal concentration of metallothionein, zinc, and copper were significantly lower than corresponding hepatic levels. The fall in hepatic levels of zinc and metallothionein during the first months of life correspond to a period of negative zinc balance and low endogenous cysteine production in the newborn. Thus metallothionein may play an important role as a storage depot for these two essential nutrients during this critical period of active growth. (Pediatr Res 24: 326-329, 1988) During the last trimester of pregnancy the mature placenta regulates the transfer of nutrients and protects the fetus from potentially toxic substances. With premature birth, the newborn infant is at risk of both nutrient deficiencies and toxicities for at least five reasons. I) Nutrient intake requirements may be unknown thus too much or too little may be provided; 2) homeostatic mechanisms in the functionally immature preterm are poorly developed; 3) the immature blood-brain bamer is more permeable to any elements present in the plasma; 4) growth is extremely rapid, thus nutrient needs are highest at the same time that nutrient stores are very low; and 5) postnatal adaptation may be prolonged for months even in the absence of overt disease. This combination of factors demand that both environmental and nutritional factors be rigidly controlled for the newborn premature infant.It has been established that most of the minerals of the human fetus are layed down during the last trimester of pregnancy (1).

Zinc Homeostasis in Premature Infants Does Not Differ Between Those Fed Preterm Formula or Fortified Human Milk

“…The high EZP mass in these premature infants seems likely to reflect the relatively high total absorbed and net absorbed zinc, both of which were significantly correlated with EZP size and which have also been observed to correlate with EZP both in term infants (26) and in adults (19). The relatively high EZP in the premature infants may also reflect, in part, the zinc bound to hepatic metallothionein, the concentrations of which have been reported to be higher in preterm than term infants, although absolute amounts are less in preterm infants (4). From the data obtained in the present study, the contribution of hepatic metallothionein bound zinc present at birth and contributing to the EZP cannot be distinguished from the contribution from absorbed dietary zinc.…”

Abnormalities in Zinc Homeostasis in Young Infants with Cystic Fibrosis

“…Estimates of the requirement for net absorption of zinc to support normal growth at this age has been estimated at approximately 0.7 mg/d (30). Healthy exclusively breast-fed 2-mo-old infants studied with similar stable isotope methods have been found to have a net zinc absorption of 0.3 mg/d (10), which supports a possible role for hepatic metallothionein as a source of zinc in the early months of postnatal life (31,32). Availability of such a "store" of zinc may also explain why reports of severe zinc deficiency, with acrodermatitis enteropathica-like rash, have generally been in infants with cystic fibrosis who were older than those in this study (1)(2)(3).…”

Nutritional and Functional Properties of Mushroom (<i>Agaricus bisporus</i> &amp; <i>Pleurotus ostreatus</i>) and Their Blends with Maize Flour

“…Increasing mushroom content resulted in increasing the zinc content for both mushroom species. Low liver reserves of zinc at birth may predispose some infants to zinc deficiency [42], similar to the situation for iron [40]. There was significant difference (p≤0.05) in the zinc density for the fortified maize flour compare to the control.…”