Effects of copper deficiency and Cu complexes on superoxide dismutase in rats.

The effect of dietary copper (Cu) deficiency on the antioxidant enzyme superoxide dismutase (SOD) was investigated in both erythrocyte and liver samples of 40 weanling Wistar rats. Groups were fed control (10 mg Cu/kg) or Cu-deficient (0.5 mg Cu/kg) diets for 7 wk. In this study, dietary copper deficiency did not affect growth, food intake, liver size, or hemoglobin levels. Protein concentrations were considerably decreased in the livers of the copper-deficient group compared to control groups after 7 wk. Erythrocyte SOD activity was not significantly different in copper-deficient groups. In contrast, SOD activity was significantly reduced in livers of rats consuming the Cu-deficient diet compared to controls. The in vitro SOD activities in the presence of five different macro-cyclic copper-II containing complexes with different stability constants were studied. The moderately stable copper complex increased the SOD activity in Cu-deficient liver and erythrocyte samples only at wk 7. At wk 6, a significant increase in SOD activity in liver samples only was observed. In contrast, at wk 4, no significant differences in SOD activity were observed upon addition of Cu complexes. These results suggest that the increase in SOD activity may be due to superoxide-like action or other properties of this copper complex.

Dietary beta-carotene reduces serum lipid concentrations in spontaneously hypertensive rats fed a vitamin A-fortified and cholesterol-enriched diet.

The effects of dietary beta-carotene on serum lipid concentrations were examined in spontaneously hypertensive (SH) rats. Groups of SH rats were fed a semipurified, vitamin A-fortified and cholesterol-enriched diet supplemented with 0, 125, 250 or 500 mg beta-carotene/kg diet for a period of 44 d. beta-Carotene supplementation resulted in significant dose-related decreases in serum total, LDL and HDL cholesterol concentrations and serum total, VLDL and LDL triacylglycerol concentrations. The ratio of HDL cholesterol to total cholesterol was unchanged or slightly increased by dietary beta-carotene. The study suggests that dietary beta-carotene has antihyperlipidemic effects in SH rats. The effects in humans and the mechanism of the effects remain to be investigated.

Effect of zinc or copper deficiency on erythrocyte purine nucleoside phosphorylase and pyruvate kinase activity in the rat.

The effect of deficiencies of zinc or copper in the rat on the activity of purine nucleoside phosphorylase and pyruvate kinase in erythrocytes, liver and muscle was investigated. The data showed no effect of either zinc or copper deficiencies on the activity of these enzymes in the tissues tested. It is concluded that these enzymes are not useful markers for either zinc or copper deficiency.

Plasma lead and erythrocyte zinc protoporphyrin in neonates and young children in Kuwait.

Blood samples from a series of 797 nonselected Kuwaiti Bedouin infants less than 5 years old were analyzed for lead (Pb) and zinc protoporphyrin (Zpp). Elevated blood Pb concentration (greater than 25 micrograms/dl), which may indicate Pb poisoning, was found in 53 cases (6.8%). These children had a mean blood Pb concentration of 47.1 +/- 15.9 micrograms/dl. The correlation coefficient between the concentration of Pb and Zpp in the blood was r = 0.78, p less than 0.001. The results indicated that Pb intoxication in neonates and children may be a significant health problem in Kuwait, and that measurement of blood Zpp can be used as a simple, rapid, and inexpensive microscreening method for Pb poisoning in infants and neonates.

Maternal plasma proteins, magnesium, zinc and copper concentration at term associated with birth size in Kuwait.

The study was carried out on Arab women who were admitted for delivery to Al-Sabah Hospital in Kuwait. The concentration of maternal serum proteins and magnesium was not correlated to infant birth size. The zinc and copper concentration in maternal serum at term was positively correlated to infant birthweight, length and head circumference. The results suggested the possibility that the mothers in the present study had a marginal zinc and copper nutriture, which when combined the hemodilution due to pregnancy led to serum levels inadequate to supply the requirement of the fast growing fetus.

Fetal malnutrition: an appraisal of correlated factors.

Fetal malnutrition has emerged as a significant health problem over the past decade. Present evidence suggests that maternal environment plays the major etiologic role in fetal malnutrition. The association of fetal malnutrition in mothers with chronic hypertension is well known, but fetal malnutrition is associated with maternal hypertension in less than 25 per cent of cases. Among a group of 182 pregnant women studied at midpregnancy for blood levels of vitamins, trace metals, proteins, amino acids, and parameters of maternal leukocyte energy metabolism, it was found that the concentration of 10 amino acids, alpha-1-globulin, zinc, and total carotenes had a statistically significant relationship to fetal growth. Similarly significant correlations were found for maternal leukocyte adenosine disphosphate, phosphofructokinase activity, ribonucleic acid (RNA) synthesis, and cell size. Maternal cigarette smoking was correlated with reduced fetal growth. Analysis showed that there was a significant reduction in leukocyte RNA synthesis and phosphokinase activity and in the plasma levels of 14 amino acids, and carotene in smoking mothers. This information lends support to the hypothesis that factors which affect the growth of fetal cells also will affect maternal leukocytes in a definable way.

Kinetic properties of pyruvate kinase in human maternal leukocytes in fetal malnutrition.

Pyruvate kinase (PK) is one of the regulatory enzymes in glycolysis. The present study was undertaken to determine whether regulation of the enzyme by normally occurring metabolites was disturbed in leukocytes of mothers who delivered fetally malnourished (FM) babies. Kinetic studies of enzyme regulation by physiologic effectors approximated a potential regulating mechanism of the enzyme in its cellular environment. There are two isoenzymes of PK. Leukocytes contain an M2 enzyme with intermediate regulatory properties between the liver (type L) and the muscle (type M) enzymes. The presence in the cell of M2 PK in the A form leads to inhibition of glycolysis by amino acids, such as alanine, and therefore, to the sparing of glucose but probably inhibition of energy production from glucose. In this study, leukocytes were isolated from blood of six pregnant women and 11 women in the postpartum period in Oklahoma and at parturition from 31 women in Mexico. Fourteen of the latter group delivered FM babies. The kinetic characteristics of the nonpurified enzyme PK with respect to allosteric modulation in fructose-1, 6-phosphate (FDP) and L-alanine (Ala) were studied in the leukocyte extracts. Data for initial reaction velocities (v) vs substrate concentrations (s), double reciprocal Lineweaver-Burk plots, and Hill plots are presented. The equations for the double reciprocal plots were determined by linear regression analysis. The enzyme constants were derived by computer, and the values compared by the Mann-Whitney U-test. In all subjects studied, 0.5 mM FDP activated and 2 mM L-alanine inhibited the enzyme. During pregnancy, the v vs s concentration curves were hyperbolic (Hill coefficient, n is less than 1.0) except for the Ala-inhibited enzyme during pregnancy, which had a sigmoid curve, n=1.54. The interaction of FDP and Ala was dependent on the concentration of the substrate phosphoenolpyruvate (PEP) at low [PEP]. There was net activation, not inhibition, at high concentrations; the switchover was at 0.5 mM PEP during pregnancy. In Mexican mothers having normal babies (normal mothers) the maximum initial velocity, V (micromoles per min per mg of DNA), with respect to PEP, was 2.22+/-0.34; in FM mothers, V was 2.01+/-0.44. With respect to binding of the substrate, PEP, V of the leukocyte enzymes in FM mothers vs normal mothers was equally inhibited by Ala (deltaV=-50% vs -47%), but was significantly less responsive to stimulation by FDP (deltaV=+10% vs +75%). When both Ala and FDP were present, FDP less effectively overcame the inhibition by Ala (deltaV=-9% vs +54%). The K0.05 of the enzyme (molar concentration X 10(-4) PEP) was significantly reduced by FDP, whether Ala was present or not, during pregnancy and in the postpartum period in leukocytes of Oklahoma mothers and at term in Mexican mothers. The K0.5 for normal and FM mothers was similar. Thus, the enzyme in leukocytes of Mexican mothers who delivered FM and normal babies exhibited different kinetic responses to the allosteric modulators...