Development of Mammalian Sulfur Metabolism: Absence of Cystathionase in Human Fetal Tissues

Abstract

ExtractCystathionase activity was absent from human fetal liver and brain as early as 6 weeks of gestation. Hepatic methionine-activating enzyme (26 ± 3 nmoles/mg protein/hr) and hepatic cystathionine synthase (21 ± 4 nmoles/mg protein/hr) were present (cf. 86 ±16 and 98 ± 19 nmoles/mg protein/hr, respectively, in mature human liver). All three activities were absent from the placenta. Human fetal liver contained higher concentrations of cystathionine (14 ± 2 /xmoles/100 g wet weight) than mature human liver (0) and human fetal brain (4.0 ± 0.6 ,umoles/100 g wet weight). Methionineactivating enzyme of human fetal brain, but not liver, showed a tendency to increase with development (coefficient of correlation was 0.62; 0.01 < P < 0.05).35 S-L-methionine injected into the umbilical vein of six human fetuses was incorporated into free methionine in liver and brain, but not into free cyst(e)ine, homocyst(e)ine, taurine or, except for the smallest fetus, cystathionine. 35S-L-cysteine similarly injected was incorporated into free cysteine in liver and brain to a greater extent than in plasma, whereas it was incorporated into cystine in plasma to a greater extent than in either liver or brain. Incorporation of S-L-cysteine incubated with minced liver from four human fetuses showed more active incorporation of methionine (11,836-15,045 dpm/mg protein) than cysteine (7,044-9,856 dpm/mg protein). SpeculationThese studies suggest that cysteine is an essential amino acid in human fetuses and in infants for some time after birth, especially if they were born prematurely. Introductionknown about the early development of these pathways. Although there is considerable information on controlIn normal adult humans, about 90% of ingested meof the metabolism of sulfur-containing amino acids thionine is converted to cyst(e)ine [21], a nonessential and transsulfuration in mature humans, little is amino acid, via the transsulfuration pathway (Fig. 1).

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

“…fetus seems to be totally dependent on maternal transfer of cysteine because of absent cystathionase activity both in the fetus and placenta (14,15). Unlike other amino acids, the concentration of cysteine is lower in the fetal than the maternal circulation (28).…”

Placental transfer and fetal uptake of amino acids in the pregnant ewe

“…[37]). N This indicates that all the amino acids are probably transferred across the placental barrier, because it is known that the enzymes converting essential to non-essential amino acids are not always active in fetal liver until after birth (JAKUBOVIC [17], and GAULL et al [8]). Experimental evidence for this transfer has been obtained in the guinea pig with the fetal placenta perfused c in situ'; each essential amino acid, with the exception of threonine and tryptophan, and the majority of non-essential amino acids, were shown to be transported from the maternal plasma, across the placental membrane against a concentration gradient (YouNG and HILL [37]): It is a well known fact that the free amino concentration in maternal plasma is low during gestation, at a time when it might be expected to be maintained to ensure a fetal supply.…”

The Biological Roles of Steroid Sulfonation

“…The increased circulating sulfate level in pregnant humans (from ≈ 0.26 to 0.59 mM) [82,88,89] and mice (from ≈ 1.0 to 2.3 mM) [83] enhances sulfate availability to the placenta and fetus, and is remarkable since most circulating ions usually decrease slightly due to haemodilution [90]. Since the placenta and fetus have a relatively low capacity to generate sulfate from methionine and cysteine [18,19], most of the sulfate in these tissues must come from the maternal circulation ( Figure 4). This is consistent with fetal hyposulfatemia and negligible amniotic fluid sulfate levels in fetuses from pregnant hyposulfataemic NaS1 null mice [83].…”

“…Certain cell types in adults, including chondrocytes, endothelial cells and hepatocytes have a high requirement for intracellular sulfonation, and are more reliant on transport of extracellular sulfate into the cell [16,17]. In addition, the placenta and developing fetus are reliant on sulfate from the maternal circulation bcause placental and fetal cells have a relatively low capacity to form sulfate from methionine and cysteine [1,18,19]. Sulfonation reactions in all organisms require the conversion of sulfate to the universal sulfonate (SO 3 -) donor, 3'-phosphoadenosine 5'phosphosulfate (PAPS) [20].…”