Amino acid metabolism during starvation in human pregnancy

Felig, Philip; Kim, Young Jin; Lynch, Vincent J.; Hendler, Rosa

doi:10.1172/jci106913

Cited by 122 publications

(73 citation statements)

References 39 publications

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“…Our data for L-methionine, L-leucine, and L-ornithine, taken together with considerable other data from a number of laboratories [3,4,8,9,11,17,21,22], is compatible with the hypothesis that, in general, amino acids are transferred from mother to fetus by a process of active transport, i.e., carrier-mediated, saturable, energy-dependent, stereospecific, and operating against a chemical gradient.…”

Section: Discussionsupporting

confidence: 88%

Transfer of Cyst(e)ine and Methionine across the Human Placenta

et al. 1973

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ExtractAfter intravenous loads in pregnant women, L-methionine, L-leucine, and L-ornithine were transferred from maternal to fetal plasma against a two-to threefold difference in initial concentration. Cyst(e)ine is unique among the free amino acids of plasma in that its basal concentration in maternal plasma was equal to or greater than that in fetal plasma. Furthermore, after intravenous loads with L-cystine or L-cysteine, total cyst(e)ine (cystine and cysteine) was transferred less readily to the fetal plasma. Although the concentrations of cystine in the fetal plasma continued to rise in the face of rapidly falling concentrations of cystine in the maternal plasma, at no time during the experiment did the concentration of cystine in fetal plasma exceed that in the maternal plasma. When D-cystine was administered intravenously to a mother, in amounts equimolar with L-cystine, the transfer of D-cystine was not measurable. SpeculationCyst(e)ine is the end-product of the transsulfuration pathway, which transfers the sulfur from the 4-carbon skeleton of methionine to the 3-carbon skeleton of serine. Methionine-activating enzyme, the first enzyme on this pathway, is inhibited by cyst(e)ine [2,5,20]. It is also allosteric [19], a characteristic often associated with negative feedback inhibition. Cystathionase, which cleaves cystathionine to cysteine and a-ketobutyrate and is the last enzyme on this pathway, is absent from the liver and brain of the human fetus. Therefore, we postulate that the special mechanism for the transfer of cyst(e)ine across the human placenta is an adaptation to control the transfer of sufficient maternal cyst(e)ine for synthesis of protein and glutathionine without undue inhibition of the activation of methionine to iS'-adenosylmethionine, a compound involved in important synthetic reactions.

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Section: Discussionsupporting

confidence: 88%

Transfer of Cyst(e)ine and Methionine across the Human Placenta

et al. 1973

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“…The current observations are also of interest with respect to the hypoalaninemia reported in normal pregnancy (20) and in ketotic hypoglycemia, a common disorder of blood glucose homeostasis observed in young children (21). In both circumstances, hypoalaninemia has been implicated in the pathogenesis of exaggerated starvation ketosis and hypoglycemia.…”

Section: Discussionmentioning

confidence: 78%

Effect of ketone infusions on amino acid and nitrogen metabolism in man.

Sherwin¹,

Hendler²,

Felig³

1975

J. Clin. Invest.

328

123

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A B S T R A C T To evaluate the role of hyperketonemia in the hypoalaninemia and decreased protein catabolism of prolonged starvation, Na DL-P-hydroxybutyrate was administered as a primed continuous 3-6-h infusion in nonobese subjects and in obese subjects in the postabsorptive state and after 3 days and 3-51 wk of starvation. An additional obese group received 12-h ketone infusions on 2 consecutive days after 5-10 wk of fasting.The ketone infusion in nonobese and obese subjects studied in the postabsorptive state resulted in total blood ketone acid levels of 1.1-1.2 mM, a 5-15 mg/100 ml decrease in plasma glucose, and unchanged levels of insulin, glucagon, lactate, and pyruvate. Plasma alanine fell by 21% (P <0.001) in 3 h. In contrast, other amino acids were stable or varied by less than 10%. Infusions lasting 6 h reduced plasma alanine by 37%, reaching levels comparable to those observed in prolonged starvation. Equimolar infusions of NaCl and/or administration of NaHCOs failed to alter plasma alanine levels.During prolonged fasting, plasma alanine, which had fallen by 40% below prefast levels, fell an additional 30% in response to the ketone infusion. In association with repeated prolonged (12 h) infusions in subjects fasted 5-10 wk, urinary nitrogen excretion fell by 30%, returning to base line after cessation of the infusions and paralleling the changes in plasma alanine. Ketone infusions resulted in two-to fourfold greater increments in blood ketone acids in fasted as compared to postabsorptive subjects.It is concluded that increased blood ketone acid levels induced by infusions of Na DL-P-hydroxybutyrate result in hypoalaninemia and in nitrogen conservation in starvation. These data suggest that hyperketonemia may be a contributory factor in the decreased availability of circulating alanine and reduction in protein catabolism characteristic of prolonged fasting. INTRODUCTIONIn fasting man survival is dependent upon the conservation of body protein stores as well as the continuous supply of energy-yielding fuels for brain metabolism (1). The need for gluconeogenesis and concomitantly the rate of protein breakdown progressively decline in prolonged starvation as ketone acids replace glucose as the major fuel consumed by the brain (2). The diminution in hepatic gluconeogenesis in prolonged fasting is mediated by a reduction in circulating glucogenic amino acids, particularly alanine, and a decrease in the outflow of these amino acids from muscle (3, 4). After a prolonged fast, plasma alanine decreases to a greater extent than that of all other amino acids, while splanchnic uptake and peripheral release of alanine are reduced to less than 50% of postabsorptive levels (3, 4).

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“…Another possibility would be decreased glucose production. Evidence exists that in the pregnant state alanine availability is reduced 21,22 . Reduced gluconeogenesis, however, has not been demonstrated 23,24 .…”

Section: Discussionmentioning

confidence: 99%

Maternal plasma glucose at high altitude

Krampl

Kametas

Zegarra

et al. 2001

BJOG

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Objective To compare plasma glucose in pregnant women living at very high altitude; pregnant women living at sea level; non-pregnant women living at very high altitude; and non-pregnant women living at sea level.Design Cross-sectional study. Participants Ninety-four pregnant women attending for routine antenatal care at 8±42 weeks of gestation in Cerro de Pasco, Peru which is situated 4370 m above sea level; 122 pregnant women in Lima, which is at sea level; 22 non-pregnant women in Cerro de Pasco; and 31 non-pregnant women in Lima. Methods Plasma glucose concentrations were measured in samples obtained from the antecubital vein between 8 am and 10 am after an overnight period of fasting for at least 10 hours. Results Fasting plasma glucose was lower in women at high altitude than in those at sea level, and in both groups the level was lower in pregnant women than in non-pregnant controls. The body mass index was not signi®-cantly different between all four groups, and it did not have a signi®cant independent contribution in explaining the variance in fasting plasma glucose.Conclusion Women native at high altitude have lower plasma glucose concentrations before and during pregnancy than those at sea level.

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Amino acid metabolism during starvation in human pregnancy

Cited by 122 publications

References 39 publications

Transfer of Cyst(e)ine and Methionine across the Human Placenta

Transfer of Cyst(e)ine and Methionine across the Human Placenta

Effect of ketone infusions on amino acid and nitrogen metabolism in man.

Maternal plasma glucose at high altitude

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