scholarly journals Placental Transport of Leucine, Phenylalanine, Glycine, and Proline in Intrauterine Growth-Restricted Pregnancies

2001 ◽  
Vol 86 (11) ◽  
pp. 5427-5432 ◽  
Author(s):  
Cinzia L. Paolini ◽  
Anna Maria Marconi ◽  
Stefania Ronzoni ◽  
Michela Di Noio ◽  
Paul V. Fennessey ◽  
...  

l-[1-13C]Leucine,[ 1-13C]glycine, l-[1-13C]phenylalanine, and l-[1-13C]proline were infused as a bolus into the maternal circulation of seven appropriate for gestational age at 30.3 ± 3.0 wk and 7 intrauterine growth-restricted pregnancies at 26.5 ± 1.0 wk gestation to investigate placental transport in vivo. Umbilical venous samples were obtained at the time of in utero fetal blood sampling at 450± 74 sec from the bolus injection. In normal pregnancies the fetal/maternal (F/M) enrichment ratios for leucine (0.76 ± 0.06) and phenylalanine (0.77 ± 0.06) were higher (P < 0.01) than the F/M ratios for glycine (0.18 ± 0.04) and proline (0.22 ± 0.02). This suggests that these two essential amino acids rapidly cross the placenta in vivo. Compared with the essentials, both glycine and proline had significantly lower F/M enrichment ratios, which were not different from each other. The results support the hypothesis that amino acids with high affinity for exchange transporters cross the placenta most rapidly. In intrauterine growth-restricted pregnancies, the F/M enrichment ratio was significantly lower (P < 0.01) for l-[1-13C]leucine (0.76 ± 0.06 vs. 0.48 ± 0.07) and for l-[1-13C]phenylalanine (0.77 ± 0.06 vs. 0.46 ± 0.07) compared with appropriate for gestational age pregnancies reflecting impaired transplacental flux. The F/M enrichment ratio did not differ for[ 1-13C]glycine (0.18 ± 0.04 vs. 0.17 ± 0.03), and l-[1-13C]proline (0.22 ± 0.02 vs. 0.18 ± 0.04).

2001 ◽  
Vol 280 (1) ◽  
pp. E31-E39 ◽  
Author(s):  
Cinzia L. Paolini ◽  
Giacomo Meschia ◽  
Paul V. Fennessey ◽  
Adrian W. Pike ◽  
Cecilia Teng ◽  
...  

Under normal physiological conditions, essential amino acids (EA) are transported from mother to fetus at different rates. The mechanisms underlying these differences include the expression of several amino acid transport systems in the placenta and the regulation of EA concentrations in maternal and fetal plasma. To study the relation of EA transplacental flux to maternal plasma concentration, isotopes of EA were injected into the circulation of pregnant ewes. Measurements of concentration and molar enrichment in maternal and fetal plasma and of umbilical plasma flow were used to calculate the ratio of transplacental pulse flux to maternal concentration (clearance) for each EA. Five EA (Met, Phe, Leu, Ile, and Val) had relatively high and similar clearances and were followed, in order of decreasing clearance, by Trp, Thr, His, and Lys. The five high-clearance EA showed strong correlation ( r 2 = 0.98) between the pulse flux and maternal concentration. The study suggests that five of the nine EA have similar affinity for a rate-limiting placental transport system that mediates rapid flux from mother to fetus, and that differences in transport rates within this group of EA are determined primarily by differences in maternal plasma concentration.


PEDIATRICS ◽  
1985 ◽  
Vol 75 (2) ◽  
pp. 413-441
Author(s):  
Joan E. Hodgman ◽  
Paul Y. K. Wu ◽  
Nathaniel B. White ◽  
Dolores A. Bryla

The infant who is small for gestational age (SGA) is more mature at birth than similar weight infants who are appropriate for gestational age (AGA). Whether the SGA infant behaves as does the larger gestationally equivalent infant, or whether there are specific changes related to intrauterine growth retardation is a matter of some interest in the understanding of the special needs of these infants. The National Institute of Child Health and Human Development (NICHD) phototherapy study provided a large newborn population for whom birth weight, gestational age at birth, and, thereby, intrauterine growth were carefully assessed. Infants who weighed 2,000 g or more at birth were included in the study only when they became jaundiced, whereas infants who weighed less than 2,000 g at birth were routinely entered into the study. Consequently, this report will be limited to the lowbirth-weight population selected by birth weight. Too few SGA babies were present in the groups with greater birth weight to allow meaningful comparisons. PATIENT SELECTIQN All infants whose birth weight was less than 2,000 g were entered into the study at 24 ± 12 hours. Those excluded from the study were: (1) infants who died before 24 hours, (2) infants with serious congenital defects, and (3) infants whose mothers refused consent for study. The study population consisted of 922 infants surviving at 24 hours. Gestational age was calculated from the first day of the last menstrual period obtained from maternal history and also by the evaluation techniques of Dubowitz.25 Intrauterine growth was determined by plotting birth weight and gestational age on the Denver Intrauterine Growth Curves8; infants below the 10th percentile were considered SGA.


1988 ◽  
Vol 117 (4) ◽  
pp. 485-490 ◽  
Author(s):  
Glen E. Hofmann ◽  
Ch. V. Rao ◽  
Fred R. Carman ◽  
Tariq A. Siddiqi

Abstract. Specific binding of 125I-human epidermal growth factor (hEGF) to homogenates of term human placentas and fetal membranes from normal and appropriate for gestational age (N = 20), intrauterine growth retarded (N = 9), twin (N = 11), White class A/B diabetic (N = 12), and large for gestational age (N = 13) pregnancies was measured. In all pregnancy states, placentas bound approximately four times more 125I-hEGF than did fetal membranes (P < 0.001). There was no significant difference in 125I-hEGF binding to fetal membranes from the various pregnancy states (P > 0.05). 125I-hEGF specific binding to placentas from intrauterine growth retarded or twin pregnancies was significantly greater compared with placentas from normal and appropriate for gestational age pregnancies (P < 0.05). The binding to placentas from pregnancies complicated by White class A/B diabetes or large for gestational age infants, on the other hand, was not significantly different from that to placentas from normal and appropriate for gestational age pregnancies. 125I-hEGF specific binding did not differ between placentas from intrauterine growth retarded or twin pregnancies (P > 0.05). Placental and fetal membrane 125I-hEGF binding did not vary with fetal sex, maternal race, placental weight, or gestational age between 37 to 42 weeks (P > 0.05). Placental but not fetal membrane 125I-hEGF binding increased with increasing infant weight when appropriate for gestational age and large for gestational age infants were included (P < 0.05, r = 0.38, N = 32) but not for intrauterine growth retarded, appropriate for gestational age, or large for gestational age infants alone.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 642-642
Author(s):  
Glory Madu ◽  
Olasunkanmi Adegoke

Abstract Objectives Branched-chain amino acids (BCAAs) are essential amino acids that are crucial for skeletal muscle anabolism. Thus, alterations in their levels are associated with muscle atrophic diseases such as cancer, chronic inflammatory and neurological disorders. Others have linked impairments in BCAA metabolism to the development of insulin resistance and its sequelae. Compared to the effects of theses amino acids, much less is known on how impairment in BCAA catabolism affects skeletal muscle. BCAA catabolism starts with the reversible transamination by the mitochondrial enzyme branched-chain aminotransferase 2 (BCAT2). This is followed by the irreversible carboxylation, catalyzed by branched-chain ketoacid dehydrogenase (BCKD) complex. We have shown that BCAT2 and BCKD are essential for the differentiation of skeletal myoblasts into myotubes. Here, we investigated the effect of depletion of BCAT2 or of E1a subunit of BCKD in differentiated myotubes. Methods On day 4 of differentiation, L6 myotubes were transfected with the following siRNA oligonucleotides: scrambled (control), BCAT2, or E1a subunit of BCKD. Results Forty-eight hours after transfection, compared to control or BCAT2 siRNA group, we observed improved myotube structure in BCKD-depleted cells. BCKD depletion augmented myofibrillar protein levels: myosin heavy chain (MHC, 2-fold) and tropomyosin (4-fold), P &lt; 0.05, n = 3. To further analyze the increase in myofibrillar protein content, we examined signaling through mTORC1 (mechanistic target of rapamycin complex 1), a vital complex necessary for skeletal muscle anabolism. BCKD depletion increased the phosphorylation of mTORC1 upstream activator AKT (52%, P &lt; 0.05, n = 3), and of mTORC1 downstream substrates by 25%-86%, consistent with the increase in myofibrillar proteins. Finally, in myotubes treated with the catabolic cytokine (tumor necrosis factor-a), BCKD depletion tended to increase the abundance of tropomyosin (a myofibrillar protein). Conclusions We showed that depletion of BCKD enhanced myofibrillar protein content and anabolic signaling.  If these data are confirmed in vivo, development of dietary and other interventions that target BCKD abundance or functions may promote muscle protein anabolism in individuals with muscle wasting conditions. Funding Sources MHRC, NSERC York U.


2020 ◽  
Vol 319 (1) ◽  
pp. H203-H212
Author(s):  
Ramón A. Lorca ◽  
Christopher J. Matarazzo ◽  
Elise S. Bales ◽  
Julie A. Houck ◽  
David J. Orlicky ◽  
...  

Intrauterine growth restriction (IUGR) impairs infant well being and increases susceptibility to later-in-life diseases for mother and child. Our study reveals a novel role for AMPK in vasodilating the myometrial artery (MA) from women residing at high altitude (>2,500 m) with appropriate for gestational age pregnancies but not in IUGR pregnancies at any altitude.


2007 ◽  
Vol 2007 ◽  
pp. 1-5 ◽  
Author(s):  
Despina D. Briana ◽  
Maria Boutsikou ◽  
Stavroula Baka ◽  
George Papadopoulos ◽  
Dimitrios Gourgiotis ◽  
...  

Monocyte chemotactic protein-1 (MCP-1) plays vital roles in immune response, angiogenesis, and pregnancy outcome. We investigated plasma MCP-1 concentrations in 40 mothers and their 20 intrauterine-growth-restricted (IUGR) and 20 appropriate-for-gestational-age (AGA) fetuses and neonates on postnatal days 1 (N1) and 4 (N4). Maternal and fetal MCP-1 concentrations were decreased (P<001andP= .018, resp.), whereas N1 MCP-1 concentrations were elevated in IUGR group (P= .012). In both groups, fetal MCP-1 concentrations were lower compared to N1 and N4 ones (P= .045,P= .012, resp., for AGA,P<.001 in each case for IUGR). Reduced maternal and fetal MCP-1 concentrations in IUGR may reflect failure of trophoblast invasion, suggesting that down-regulation of MCP-1 may be involved in the pathogenesis of IUGR. Increased MCP-1 concentrations in IUGR neonates and higher postnatal ones in all infants may be attributed to gradual initiation of ex utero angiogenesis, which is possibly enhanced in IUGR.


1970 ◽  
Vol 47 (3) ◽  
pp. 347-356 ◽  
Author(s):  
R. D. G. MILNER

SUMMARY Pieces of rabbit pancreas were incubated in vitro in an incubation medium containing no glucose or 1·5 mg. glucose/ml. In each of these conditions the effect on insulin release of each of the essential amino acids at 5 mm concentration was studied. Leucine was the only essential amino acid that stimulated insulin release to a level which reached statistical significance in an incubation medium containing no glucose. In medium containing 1·5 mg. glucose/ml., arginine, isoleucine, leucine and lysine stimulated insulin release and phenylalanine inhibited insulin release. Glucagon, theophylline or dibutyryl cyclic adenosine monophosphate stimulated insulin release significantly in the presence of leucine but not in the presence of arginine. Arginine stimulated insulin release in the presence of leucine. The results of these experiments characterize further the difference in the mechanism of action of leucine and arginine on the pancreatic β-cell and indicate possible explanations for results obtained in other species in vivo.


1992 ◽  
Vol 263 (5) ◽  
pp. E928-E934 ◽  
Author(s):  
K. S. Nair ◽  
R. G. Schwartz ◽  
S. Welle

Leucine has been proposed as an in vivo regulator of protein metabolism, although the evidence for this in humans remains inconclusive. To test this hypothesis, we infused either L-leucine (154 +/- 1 mumol.kg-1 x h-1) or saline intravenously in six healthy men in two separate studies. L-Leucine infusion increased plasma concentrations of leucine and alpha-ketoisocaproate from 112 +/- 6 and 38 +/- 3 mumol/l to 480 +/- 27 (P < 0.001) and 94 +/- 13 mumol/l (P < 0.001), respectively, without any significant change in circulating insulin or C peptide levels. Leucine infusion decreased plasma concentrations of several amino acids and decreased whole body valine flux and valine oxidation (using L-[1-13C]valine as a tracer) and phenylalanine flux (using [2H5]-phenylalanine as a tracer). According to arteriovenous differences across the leg, the net balance of phenylalanine, valine, and lysine shifted toward greater retention during leucine infusion, whereas alanine balance did not change. Valine release and phenylalanine release from the leg (estimated from the dilution of respective tracers) decreased, indicating inhibition of protein degradation by leucine infusion. We conclude that leucine decreases protein degradation in humans and that this decreased protein degradation during leucine infusion contributes to the decrease in plasma essential amino acids. This study suggests a potential role for leucine as a regulator of protein metabolism in humans.


1985 ◽  
Vol 68 (4) ◽  
pp. 395-399 ◽  
Author(s):  
Karen Simmer ◽  
R. P. H. Thompson

1. The levels of zinc in plasma, erythrocytes, polymorphonuclear (PMN) and mononuclear (MN) white cells were measured after delivery in women giving birth to appropriate-for-gestational-age (AGA) babies (group I mothers), or small-for-gestational-age (SGA) babies (group II mothers) and in non-pregnant controls. 2. Mean maternal plasma zinc and albumin levels 24-48 h after delivery were lower than in controls, but PMN and MN zinc levels were unchanged. PMN zinc levels were lower than those of MN cells. 3. PMN and MN zinc levels were significantly lower in group II mothers than in group I, irrespective of smoking habits. There were no racial differences in peripheral white cell zinc levels. 4. PMN, and to a lesser degree MN, zinc levels were lower in smoking than in non-smoking mothers. 5. Erythrocyte zinc did not correlate with other zinc measurements nor with the size of the babies. Fetal erythrocyte zinc levels were one-third of maternal levels. 6. A combination of smoking and/or low PMN zinc levels selects 85% of mothers having small-for-gestational-age babies.


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