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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).