Nitrogen Balance Protein Turnover and Protein Synthesis

According to animal data, only about 80% of the nitrogen content of the fetus is found in protein; the rest is found in urea, ammonia, and free amino acids. Additional nitrogen requirements for urea excretion and for other possible nitrogen excretion products are not known for human fetuses.

Radioactive and stable isotopic tracers of selected amino acids, especially essential amino acids such as leucine and lysine, have been used to measure fetal protein synthesis, breakdown, and accretion. Limited human data is consistent with data in the fetal sheep, the only species studied in significant detail. Figure 4 shows results of experiments in fetal sheep over the second half of gestation, comparing fractional protein synthesis rates derived from tracer data and fractional body growth rates derived from body composition data. Whole body weight-specific protein turnover rate is higher in the early-gestation fetus primarily from increased rates of amino acid uptake from the placenta (exogenous entry of amino acids into the fetal circulation) and protein synthesis. These processes produce a 50% higher rate of net protein accretion in the mid-gestation fetus.

Mechanisms underlying the decrease in protein synthesis rate over gestation are not well understood, but they appear to be intrinsic to the fetus and not to a limitation of nutrient supply by the

Table 2 Fetal organ weight as per cent of body weight

50% Gestation 67% Gestation 90% Gestation

80 100 120 140 Fetal age (days)

80 100 120 140 Fetal age (days)

Figure 4 Fractional rate of protein synthesis (Ks) over gestation in fetal sheep studied with leucine (•) and lysine (O) radioactive tracers compared with the fractional rate of growth (KG) (lower portion of the figure, —). (Reproduced with permission from Hay WW Jr (1992) Fetal requirements and placental transfer of nitrogenous compounds. In: Polin RA and Fox WW (eds.) Fetal and Neonatal Physiology, p. 439. Philadelphia: W.B. Saunders.)

Table 2 Fetal organ weight as per cent of body weight

50% Gestation 67% Gestation 90% Gestation

Liver

6.5

5.1

3.1

Kidneys

1.6

1.2

0.7

Heart

0.9

0.8

0.8

Brain

3.4

2.9

1.7

Hindquarters

14.5

15.1

22.0

Reproduced with permission from Bell AW et al. (1987) Relation between metabolic rate and body size in the ovine fetus. Journal of Nutrition 117: 1181-1186. Used with permission.

Reproduced with permission from Bell AW et al. (1987) Relation between metabolic rate and body size in the ovine fetus. Journal of Nutrition 117: 1181-1186. Used with permission.

placenta. At least a partial explanation can be offered according to the changing proportion of body mass contributed by the major organs (Table 2). Based on the increased mass of skeletal muscle with advancing gestation, fetal whole body fractional synthesis rate should be lower, as skeletal muscle has a relatively lower fractional protein synthetic rate in late gestation than in earlier gestation. A direct relationship between anabolic growth-promoting substances acting as principal regulators of fetal protein synthesis rate, and thus fetal growth rate, cannot be made, however, as plasma concentrations or secretion rates of these substances increase in the fetus as gestation proceeds, while protein synthetic rates decline.

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