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A specific tyrosine aminotransferase, separate from the aspartate aminotransferases, is present in low concentration in foetal rat liver at the 21st day of gestation. Intraperitoneal injections of tyrosine methyl ester into the foetuses in utero increase the activity 2-fold, whereas glucose injections decrease it. Tyrosine, dexamethasone and dibutyryl cyclic AMP induce the enzyme activity in organ culture to the same extent as in adult rat liver in vivo.

Unfortified human milk does not normally provide enough protein to secure maximal growth in low-body-weight (LBW) infants. Due to the practical difficulties in obtaining human milk protein (HMP), a bovine milk protein preparation (BMP) was designed by computer calculation to contain as close as possible the amino acid composition of the nutritionally available human milk proteins. Twenty-one AGA, LBW infants (BW of 1,180 to 1,600 g, GA of 27 to 33 weeks) were randomly assigned to be fed HM enriched either with HMP (9 infants) or BMP (12 infants). When full volume intake (170 ml/kg/day) was reached, the protein intakes were 3.6 ± 0.5 and 3.3 ± 0.3 g/kg/day, respectively, in the two diet groups. During the study period of 24 days, the infants achieved intrauterine or better weight gains: 32.9 ± 3.3 g/day (17.7 ± 1.9 g/kg/day) in the HMP group and 34.7 ± 7.3 g/day (18.3 ± 3.5 g/kg/day) in the BMP group. Serum urea nitrogen, acid-base status, and albumin values were normal and similar in both groups of infants. Plasma concentrations of total essential and total amino acids at the end of the study were 3,999 and 1,539 μmol/L and 3,899 and 1,422 μmol/L in the HMP and the BMP groups, respectively. The concentrations of all individual plasma amino acids were similar in both feeding groups. These results show that feeding human milk fortified with a modified bovine milk protein preparation produces satisfactory growth and a plasma amino acid profile similar to that found in LBW infants fed exclusively human milk protein at similar intakes.

Several recent studies have demonstrated significantly lower plasma total tryptophan concentrations in formula-fed than in breast-fed infants. We have measured preprandial plasma amino acid concentrations in infants breast-fed or fed a formula with a protein concentration of 1–57 g/dl and with a whey/casein ratio of 60:40 or a formula with a protein concentration of 1.37 g/dl and a whey/casein ratio of 40:60 and fortified with 10 mg/dl (15 mg/100 kcal) of tryptophan. Healthy term infants (10 per group) were either breast-fed from birth or randomly assigned to one of the two study formulas. At 4 and 12 weeks of age, anthropometric measurements were performed and blood samples were obtained. During the study period of 12 weeks, all infants showed normal growth (weight, length, and head circumference) and there were no statistically significant differences between the groups. The plasma concentrations of the essential amino acids phenylalanine, threonine, valine, and lysine were significantly lower in the breast-fed group than in both formula-fed groups. For tyrosine, methionine, leucine, histidine, isoleucine, and arginine, no significant differences could be found between the feeding groups. Concentration of total plasma tryptophan was significantly higher in the breast-fed group than in the group fed the tryptophan-unfortified formula, but no statistically significant difference could be found between the plasma tryptophan concentration in the breast-fed group versus the group fed the tryptophan-fortified formula. The results indicate that tryptophan fortification of adapted formula is necessary to achieve plasma total tryptophan concentrations similar to those found in breast-fed infants. The data also confirm that a formula with reduced protein concentration will support normal growth and will produce a plasma amino acid profile not much different from that of a conventional type of formula.

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Extract: Explants of fetal rat (13 days to term) and fetal human liver (crown to rump length = 9–20 cm) were grown in organ culture. The survival of the explants was examined by histological appearance, mitotic index, and incorporation of precursors of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein. Tissues adjusted to the culture system by the 24th hr and remained so throughout the duration of the experiments. A slight increase in tyrosine transaminase activity occurred in control explants during the 3-day period in culture. Eighteen-hour incubation with hydrocortisone (10-6M), glucagon (5–25 µg/ml), and insulin (0.05–0.5 U/ml) increased tyrosine transaminase levels, 3.1–6.5, 2.5, and 2.3 times the control values, respectively, in 18-day to term fetal rat liver explants. Actinomycin D and cycloheximide completely inhibited the corticosteroid stimulation. Thirteen-day fetal rat liver exhibited no increase in tyrosine transaminase activity after hydrocortisone incubation for 24 hr, whereas glucagon plus dibutyryl cyclic adenosine monophosphate (AMP) did stimulate tyrosine transaminase activity twofold at this developmental stage. No increase in human fetal liver tyrosine transaminase occurred with any of the agents tested.Speculation: These studies support the hypothesis that mammalian liver is incompetent to respond to hormone-induced enzyme synthesis before a certain developmental stage is reached.

Extract: In the present study, alcohol dehydrogenase activity (ADH) has been measured in human liver tissue during development, and a comparison made between certain kinetic properties of crude enzyme preparations from fetal and adult liver.The fetal livers were obtained from legal abortions. The liver tissue from children and adults was acquired during surgery of the abdomen in cases where no macroscopic abnormality of the livers was observable. The liver tissue was frozen immediately after excision. Studies indicated that the enzyme activity was stable at −20° for up to 6 days. All the determinations were made within 24 hours of the liver being sampled.A 10% liver homogenate was prepared in ice-cold 0.25 M sucrose containing 1 % Triton X-100. After centrifugation of the homogenate for 10 minutes at 5000 × g at 3°C, samples were taken from the supernatant for protein determination and for enzyme assays. Table I presents the enzyme activity levels in human liver during the development from a fetus to an adult organism. The results are expressed as milliunits per g liver wet weight and per 100 mg soluble liver protein. ADH activity is detectable in 2-month-old fetuses, although it amounts to no more than 3–4: % of adult activity. Activities of adult range are found after 5 years of age. Considerable varation exists in the activity of adult livers.The relationship between pH and the rate of reaction appears in figure 1. The final pH figures of the reaction mixtures are given; these were determined with a Radiometer pH meter. Adult human liver ADH has a pH optimum of about 10.4, and the pH optimum for the fetal enzyme preparations is 10.0.Lineweaver-Burk analyses which illustrate the relationship between the concentration of ethanol and NAD, and the ADH activity in adult and fetal liver are presented in figures 2 and 3. The results presented are typical of three cases studied in each group. Close agreement was found for all constants in the different enzyme preparations examined. The apparent Kmvalues for ethanol were 3400 μM. and 1100 μM, and for NAD 70 μM and 150 μM in fetal and adult enzyme preparations respectively.Speculation: These results do not constitute a foundation for a conclusion whether the fetal and the adult enzyme preparations are composed of a similar isoenzyme pattern. Studies which make use of purified enzyme and isoenzyme preparations are needed. Nevertheless, the results presented here suggest that variants may be found in alcohol dehydrogenase during development.