Amino Acid (System A) Transporter Activity in Microvillous Membrane Vesicles from the Placentas of Appropriate and Small for Gestational Age Babies

Abstract

ABSTRACT. Although a number of causes of poor fetal growth are known, the involvement of placental transport proteins in the etiology of growth retardation is not undcrstood. The aim of this study was to investigate the activity of the system A amino acid transporter and the Na+/li+ eschanger in vesicles isolated from the microvillous membrane of the syncytiotrophoblast of placentas of appropriate and small for gestational age babies. l'here were no biochemical differences bet~veen the membranes from the two groups of placentas, and there was no difference in the activity of the Na+/I1+ exchanger. The initial rate of uptake of methylaminoisobutyric acid (a nonmetabolizable amino acid analogue) was 63% loner in vesicles from placentas of small for gestational age babies. Kinetic analysis of the system A transporter (utilized by mcthylaminoisobutyric acid) showed that the V,,., in the vesicles from placentas of small for gestational age babies (0.24 f 0.03 nmol/mg protein/30 s, n = 5) was significantly lower than that in vesicles from placentas of appropriate for gestational age babies (0.64 + 0.09 nmol/mg protein/30 s, n = 4, p < 0.001), whereas the Km was not different between the two groups. It is concluded that there is an abnormality of system A amino acid transporter function in placentas of small for gestational age babies. (Pediatr Res 34: 661-665, 1993)

Placental transporter activity and expression in relation to fetal growth

“…However, Dicke & Henderson (1988) did not determine whether it was Na+-dependent uptake of AIB that was affected in the small babies nor what kinetic parameters were altered. We therefore investigated the kinetics of Na+-dependent methyl-aminoisobutyric acid (MeAlB, a substrate almost exclusively transported by system A) uptake by microvillous membrane vesicles froin placentas of SGA and normally grown babies born at term (Mahendran, Donnai, Glazier, D'Souza, Boyd & Sibley, 1993). Our data show that Na+-dependent, but not Na+-independent, MeAIB uptake is reduced in the vesicles from the SGA babies and that it is the Vmax of this transporter, not the Kn,, which is significantly lower (Fig.…”

Fetal growth restriction: a workshop report

“…Consequently, studies of isolated microvillous (MVM) and basal plasma membranes (BM) may provide valuable information concerning transplacental transport processes. In MVM isolated from small-for gestational age babies the activity of the amino acid transporter system A was shown to be markedly reduced [11]. Intrauterine growth restriction is also associated with a reduced activity/expression of placental transport systems for essential amino acids, such as taurine, leucine and cationic amino acids.…”

Placental amino acid transport systems and fetal growth restriction – A workshop report

“…It is interesting to note that while sodium is required for the transport of the neutral amino acids, it is not required for the cationic amino acids arginine and lysine. These three systems exist on both membranes and have been studied in a range of unfavorable situations, including FGR [6,7,20] and situations of hypoxia [21], where reductions in activity are reported. One of the interesting observations of these studies is that the major deficits of activity in FGR is not a change in affinity, but reductions in the V max of these systems of between 30 and 60% [6,7].…”

“…These three systems exist on both membranes and have been studied in a range of unfavorable situations, including FGR [6,7,20] and situations of hypoxia [21], where reductions in activity are reported. One of the interesting observations of these studies is that the major deficits of activity in FGR is not a change in affinity, but reductions in the V max of these systems of between 30 and 60% [6,7]. Possible explanations of this reduced activity include induced changes in mRNA transcription, translational efficiency, possible alterations in the expression of protein particularly in aspects of trafficking and recruitment from intracellular compartment.…”

“…The recent demonstration that FGR is characterized by specific alterations in a number of placental nutrient transporters may offer a novel approach for diagnosis. In particular, decreased activity of system A has been suggested to represent a marker for FGR since system A activity has been shown to be down-regulated in microvillous plasma membranes isolated from FGR placentas in several studies [7,25,26]. However, some observations suggest a rather complex relationship between placental system A activity and fetal growth.…”