Free Amino Acids of Human Foetal and Adult Liver

Ryan, Wayne L.; Carver, Michael J.

doi:10.1038/212292a0

Cited by 59 publications

(36 citation statements)

References 8 publications

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“…The placenta is an active metabolic organ with significant oxygen requirements (3) and involved in the synthesis of large amounts of protein. Similar amino acid concentrations have been reported in other active metabolic organs such as liver, brain, and muscle (1, 14,15).…”

Section: L-leucine L-aspartic Acid Discussionsupporting

confidence: 56%

Transfer of Amino Acids across the In Vitro Perfused Human Placenta

Schneider

Dancis

1979

Pediatr Res

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SummaryAmino acid transfer across human placenta has been studied in an in vitro perfusion system. Transfer rates from maternal to fetal circuit of 12 amino acids were about the same when there was a downhill gradient permitting diffusion and active transport. This was termed "maximal transfer rate." Cystine, aspartic acid, and glutamic acid were transferred a t approximately half the rate of the others under these conditions. Measurement of exchange rates with radioactive tracers and with equimolar concentration of amino acids on both sides of the membrane provided a close estimate of maximal transfer rate. Fetal nutrition requires active transfer against a gradient. The rate of active transfer is a fraction of the exchange rate.The ability to establish a transplacental gradient by perfused placenta was investigated with the maternal circuit open and fetal circuit closed (recirculated). The fetal to maternal concentration ratio for D-leucine and antipyrine was 1.0, for L-leucine, 1.5, indicating a stereospecific transport mechanism for leucine. Cradients of 1.56 + 0.11 and 1.62 +. 0.10 were demonstrated for Lalanine and L-lysine, respectively. The establishment of transplacental gradients is a placental function, requiring no assistance using a variety of experimental techniques and experimental animals. Studies in the human have been extremely limited. Slices and fragments of human placenta have been used in vitro to measure amino acid transport (1 I, 12, 16, 19), but the pertinence of the observations to transplacental transport is uncertain. Page et al. (13) have infused D-and L-histidine into several mothers shortly before delivery and have measured the relative concentrations of the stereoisomers in the cord blood at birth. They deduced that L-histidine was transferred more rapidly than the D-isomer. Gaull et al. (7) have studied transfer rates of the sulfur-amino acids during the second trimester in elective abortions.For the past several years, we have been studying transplacental transport by perfusing a n isolated cotyledon of human placenta. Independent maternal and fetal circulations are established permitting the investigation of transfer in either direction. This technique has now been applied to the study of amino acid transport in a n attempt to answer such fundamental questions as the relation of exchange rates to net transfer, the pertinence of in vitro placental uptake studies to transplacental transport, the polarity of the placental membrane, and the possible reserve functions of the large intraplacental concentrations of amino acids. from maternal or fetal factors.The ratios of the exchange rates for the L and D-isomers were MATERIALS AND METHODS determined as a measure of the active, stereospecific transport system. The L:D ratio from the maternal to fetal circulation for PERFUSION TECHNIQUE leucine was 1.64 f 0.19, for alanine 1.78 + 0.49. In the reverse ~h~ technique of dual perfusion of the human placental cotydirection, the ratio for leucine was 1.03. The placental membrane ledon ha...

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Section: L-leucine L-aspartic Acid Discussionsupporting

confidence: 56%

Transfer of Amino Acids across the In Vitro Perfused Human Placenta

Schneider

Dancis

1979

Pediatr Res

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“…The latter finding in the 24 fetuses that we studied confirms the findings in the 2 fetuses studied by Okumura et al [18]. Our results differ from those of Ryan and Carver [22] who reported concentrations of methionine in human fetal liver (22-24 weeks of gestation) which are far higher than any that we found. They made no mention of cystathionine; however, the analytical method that they employed might not separate adequately methionine and cystathionine.…”

Section: Concentrations Of Cystathionine In Tissues and Fluidscontrasting

confidence: 57%

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

1972

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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).

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“…The flux through GCS may be underestimated in this experiment, because the concentration of accumulated glycine reached to only 0.07-0.12 mM, whereas its concentration in rat liver in vivo was thought to be maintained at ϳ2.5 mol/g (34) by active transport and net uptake from the bloodstream, in addition to the supply from serine. However, when 2.5 mM [1-14 C]glycine was incubated with a mitochondrial suspension (a suspension of 8200 ϫ g precipitate) corresponding to 40 mg of tissue, the amounts of 14 CO 2 evolved were ϳ55 nmol/60 min for both 24-h starved rats and glucagon-treated rats.…”

Section: Relative Contributions Of the Three Pathways To The Metabolimentioning

confidence: 99%

Flux of the l-Serine Metabolism in Rat Liver

Xue¹,

Fujie

Sakaguchi

et al. 1999

Journal of Biological Chemistry

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L-Serine metabolism in rat liver was investigated, focusing on the relative contributions of the three pathways, one initiated by L-serine dehydratase (SDH), another by serine: pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT), and the other involving serine hydroxymethyltransferase and the mitochondrial glycine cleavage enzyme system (GCS). Because serine hydroxymethyltransferase is responsible for the interconversion between serine and glycine, SDH, SPT/AGT, and GCS were considered to be the metabolic exits of the serine-glycine pool. In vitro, flux through SDH was predominant in both 24-h starved and glucagontreated rats. Flux through SPT/AGT was enhanced by glucagon administration, but even after the induction, its contribution under quasi-physiological conditions (1 mM L-serine and 0.25 mM pyruvate) was about 1 ⁄10 of that through SDH. Flux through GCS accounted for only several percent of the amount of L-serine metabolized. Relative contributions of SDH and SPT/AGT to gluconeogenesis from L-serine were evaluated in vivo based on the principle that 3 H at the 3 position of L-serine is mostly removed in the SDH pathway, whereas it is largely retained in the SPT/AGT pathway. The results showed that SPT/AGT contributed only 10-20% even after the enhancement of its activity by glucagon. These results suggested that SDH is the major metabolic exit of L-serine in rat liver.

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Free Amino Acids of Human Foetal and Adult Liver

Cited by 59 publications

References 8 publications

Transfer of Amino Acids across the In Vitro Perfused Human Placenta

Transfer of Amino Acids across the In Vitro Perfused Human Placenta

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

Flux of the l-Serine Metabolism in Rat Liver

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