David K. Rassin

Milk protein quantity and quality in low-birth-weight infants. III. Effects on sulfur amino acids in plasma and urine.

The optimal quantity and quality of protein for low-birth-weight infants is undefined. In this study, 106 well, appropriate-for-gestational-age, low-birth-weight infants weighing 2,100 gm or less were divided into three gestational age groups and assigned randomly within each age group to one of five feeding regimens: pooled human milk; formula 1 (protein content, 1.5 gm/100 ml- 60 parts bovine whey proteins to 40 parts bovine caseins); formula 2 (3.0 gm/100 ml, 60:40); formula 3 (1.5 gm/100 ml, 18:82); and formula 4 (3.0 gm/100 ml, 18:82). The concentrations of the free amino aicds in the plasma and urine of these infants were determined. The plasma concentrations of free amino acids were generally far greater in the infants fed the 3.0-gm/100 ml protein diets than they were in the infants fed pooled human milk. The plasma concentrations of free amino acids of the infants fed the 1.5-gm/100 ml protein diets were intermediate. In general, the concentrations of the free amino acids in the plasma of the infants fed the 3.0-gm/100 ml casein-predominant formula (F4) were furthest from those fed pooled human milk. Glutamate showed the highest plasma amino acid concentrations in infants fed the 3.0-gm/100 ml casein-predominant formula (F4) were furthest from those fed pooled human milk. Glutamate showed the highest plasma amino acid concentrations in infants fed both the high- and low-protein casein-predominant formulas. This was true despite the fact that the intake of glutamate on the high-protein, whey-predominant formula was twice that on the low-protein, casein-predominant formula. The differences between groups in the essential amino acids in plasma were generally greater than those of the nonessential amino acids. The concentrations of amino acids in the urine tended to parallel those of the plasma.

Taurine and other free amino acids in milk of man and other mammals

Taurine and other free amino acids have been determined in human milk of a number of other species. Taurine is the most abundant free amino acid in the milk of the gerbil, mouse, cat, dog and rhesus monkey. Taurine is the second most abundant amino acid in the milk of the rat, baboon, chimpanzee, sheep, Java monkey and man. Taurine is not a major constituent in the milk of the guinea pig, rabbit, cow and horse. The milk of each species has a characteristic free amino acid pattern which may be an indication of the relative nutritional importance of these compounds during early postnatal development.

TAURINE IN DEVELOPING RAT BRAIN: MATERNAL-FETAL TRANSFER OF [35S]TAURINE AND ITS FATE IN THE NEONATE

The transfer of [35] taunne, injected intrapentoneally into pregnant rats (near term), to fetal tissues has been measured. Taurine can enter fetal brain as easily as it can fetal liver. In contrast, it cannot enter mature brain as easily as it can enter mature liver. After birth, [35S] taurine, which had been injected into the dam before birth of the pups, continues to accumulate in the brain of the pups for some days. During the neonatal period, the concentration of taurine is decreasing, but the total pool of taurine in the brain is increasing rapidly. In order to help supply this increasing pool, the taurine present in the brain at birth appears to be conserved and an increasing amount of taurine is synthesized in situ. The net result during the neonatal period of development is that brain taurine specific radioactivity decreases and brain taurine has a very slow rate of turnover.

Taurine in developing rat brain: subcellular distribution and association with synaptic vesicles of [35S]taurine in maternal, fetal and neonatal rat brain

The concentration of taurine in the brain of the fetus in several species is higher than that found in the mature animal. In order to explore the functional significance of this, we have studied the subcellular distribution of taurine and [35S]taurine in the brain of the mother, the fetus and the neonate after [35S]taurine was administered to pregnant rats.

Pathogenesis of Brain Dysfunction in Inborn Errors of Amino Acid Metabolism

It is now only four decades since Folling’s original description of the condition he termed Imbecillitas phenylpyrouvica,(1) or phenylpyruvic oligophrenia, which was the first clear association of an inherited disorder of amino acid metabolism with brain dysfunction. The precise identification by Jervis of the enzymatic etiology, the deficiency of Phenylalanine 4-hydroxylase (EC 1.14.16.1),(2,3)1 waited two decades. In the subsequent two decades a large number of inherited disorders have been described, and in many cases the enzymatic etiology has been defined. So far, all of these disorders have involved defects in the pathways of degradation or in the conversion of one amino acid to another. In many, but not in all, the deficient enzyme is extracerebral—at least there has been no definite evidence of an intracerebral enzymatic defect. In parallel with this recent explosion of information on genetic etiology, there has been an explosion of information in neurobiology. However, information relating these two areas—i.e., how the enzymatic deficiency results in the brain disease—has not been clear-cut. Indeed, in no instance are we able to relate clearly the inherited enzymatic defect with the neurological deficit.

Taurine in Developing Rhesus Monkey Brain

The concentrations of taurine in all regions of fetal and neonatal rhesus monkey brain are greater than in the same regions of adult monkey brain. [35S]Taurine injected into pregnant rhesus monkeys is accumulated by the fetus. This process occurs rapidly in most tissues, but occurs slowly in fetal brain. Neonatal rhesus monkey brain also accumulates [35S]taurine slowly compared with other tissues after i.v. injection, and continues to accumulate [35S]taurine for a long period of time. These results suggest that the accumulation and exchange of taurine in developing rhesus monkey brain is slow, as found in neonatal rats, and that if there is a period of development at which rapid exchange of brain taurine occurs in the rhesus monkey, it is before the rapid brain growth spurt.

Taurine in Infant Nutrition

Taurine (fig. 1) is one of the most abundant amino acids in the body (1), with the largest pool present in muscle. In mammals, taurine and inorganic sulfate are the major end products of methionine metabolism (fig. 2). Despite the fact that taurine is both ubiquitous and abundant, it takes part in few known biochemical reactions. Considerable taurine is conjugated with bile acids in liver (1), but other biochemical reactions take place to a very limited extent, if at all (2). Although there are numerous proposals for alternative pathways for the biosynthesis of taurine (cf. 2), the enzyme immediately responsible for its synthesis in physiologically significant amounts is cysteinesulfinic acid decarboxylase. There are large differences amongst species in the in vitro activity of this enzyme, as there are in the concentration of taurine itself (1). For example, the activity of cysteinesulfinic acid decarboxylase, as measured in our laboratory, is 1000-fold higher in adult rat liver than in adult human liver (table 1).

Free amino acids in liver of patients with homocystinuria due to cystathionine synthase deficiency: effects of vitamin B6.

Patients with homocystinuria due to cystathionine synthase deficiency do not have free homocystine in the liver when it is present in high concentrations in the plasma and the urine. The liver of these patients is capable of maintaining normal concentrations of cystine at a time when the plasma cystine concentration is severely reduced. There is an increase in the methionine concentration of the liver which is reduced to normal concentrations during pyridoxine therapy.

Taurine in Human Nutrition and Development

Despite intensive studies by a number of investigators the functions of taurine, and, in particular, the reason for the large amounts found in most mammalian tissues remain unknown. Taurine has been associated with many different biological functions (Jacobsen and Smith, 1968; Huxtable and Barbeau, 1976; Barbeau and Huxtable, 1978) but only its role in conjugating with bile acids is well established. We have concentrated upon possible functions of taurine during development. If taurine is of importance to the brain it is during this vulnerable period that a failure to supply adequate amounts of this compound might have the most long-lasting effects. Thus, the study of the transfer of taurine to the fetus and taurine nutrition in the neonate is of considerable potential importance.