Homocysteine transport by systems L, A and y<sup>+</sup>L across the microvillous plasma membrane of human placenta

Tsitsiou, Eleni; Sibley, Colin P.; D'Souza, S W; Catanescu, Otilia; Jacobsen, Donald W.; Glazier, Jocelyn D.

doi:10.1113/jphysiol.2009.173393

Cited by 35 publications

(41 citation statements)

References 59 publications

(109 reference statements)

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“…In this context, it is noteworthy that Hcy can elicit dilation in other vessel types in a dose-dependent manner. 47 Homocysteine in the umbilical venous circulation could originate either from maternal plasma by placental transport of tHcy, 48,49 with maternal tHcy concentration predicting tHcy in cord blood, 4,35,36,50,51 or alternatively could be generated by placental metabolism, perhaps reflective of placental methylation capacity. 1,49 However, there was no apparent influence of tHcy in the fetal circulation on neonatal BP, suggesting that the associations may reflect vessel-specific phenomena.…”

Section: Discussionmentioning

confidence: 99%

Human Placental Arterial Distensibility, Birth Weight, and Body Size Are Positively Related to Fetal Homocysteine Concentration

et al. 2017

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Methionine demethylation during metabolism generates homocysteine (Hcy) and its remethylation requires folate and cobalamin. Elevated Hcy concentrations are associated with vascular-related complications of pregnancy, including increased vascular stiffness, predictive of clinical vascular disease. Maternal and fetal total Hcy (tHcy) concentrations are positively related, yet the influence of Hcy on fetoplacental vascular function in normal pregnancy has not been examined. We hypothesized that Hcy alters fetoplacental vascular characteristics with influences on fetal growth outcomes. We investigated (1) placental chorionic plate artery distensibility and neonatal blood pressure in relation to umbilical plasma tHcy; (2) relationships between cord venous (CV) and cord arterial (CA) plasma tHcy, folate, and cobalamin concentrations; and (3) tHcy associations with birth weight and anthropometric measurements of body size as indices of fetal growth in normal pregnancies with appropriate weight-for-gestational age newborns. Maternal plasma tHcy, folate, and cobalamin concentrations were consistent with published data. Placental chorionic plate artery distensibility index (β; measure of vessel stiffness) was inversely related to CA tHcy, yet neonatal blood pressure was not significantly affected. CV and CA tHcy concentrations were positively related and CV tHcy negatively related to CV cobalamin but not folate. CV tHcy concentration positively related to birth weight, corrected birth weight percentile, length, head circumference, and mid-arm circumference of newborns. CV cobalamin was inversely related to fetal growth indices but not to folate concentration. Our study demonstrates a potential relationship between fetal tHcy and placental artery distensibility, placing clinical relevance to cobalamin in influencing Hcy concentration and maintaining low vascular resistance to facilitate nutrient exchange favorable to fetal growth.

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Section: Discussionmentioning

confidence: 99%

Human Placental Arterial Distensibility, Birth Weight, and Body Size Are Positively Related to Fetal Homocysteine Concentration

et al. 2017

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“…The significantly lower concentration of total homocysteine in the umbilical artery vs. umbilical vein suggests utilization of homocysteine by the human fetus at term gestation (Malinov et al, 1998). Studies of isolated microvillous plasma membrane of human placenta show that homocysteine is transported across the placenta using system L, A, and y + L amino acid transporters with affinities similar to endogenous amino acids (Tsitsiou et al, 2009, 2011). Of these system L constitutes the primary transport system.…”

Section: One Carbon Metabolism In Pregnancymentioning

confidence: 99%

“…Of these system L constitutes the primary transport system. Interestingly homocysteine could competitively inhibit transport of other amino acid raising the possibility of impacting syncitiotrophoblast metabolism and function as well as impacting fetal supply of essential nutrients (Tsitsiou et al, 2009). …”

Section: One Carbon Metabolism In Pregnancymentioning

confidence: 99%

One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health

Kalhan

2016

Molecular and Cellular Endocrinology

102

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One carbon metabolism or methyl transfer, a crucial component of metabolism in all cells and tissues, supports the critical function of synthesis of purines, thymidylate and methylation via multiple methyl transferases driven by the ubiquitous methyl donor s-adenosylmethionine. Serine is the primary methyl donor to the one carbon pool. Intracellular folates and methionine metabolism are the critical components of one carbon transfer. Methionine metabolism requires vitamin B12, B6 as cofactors and is modulated by endocrine signals and is responsive to nutrient intake. Perturbations in one carbon transfer can have profound effects on cell proliferation, growth and function. Epidemiological studies in humans and experimental model have established a strong relationship between impaired fetal growth and the immediate and long term consequences to the health of the offspring. It is speculated that during development, maternal environmental and nutrient influences by their effects on one carbon transfer can impact the health of the mother, impair growth and reprogram metabolism of the fetus, and cause long term morbidity in the offspring. The potential for such effects is underscored by the unique responses in methionine metabolism in the human mother during pregnancy, the absence of transsulfuration activity in the fetus, ontogeny of methionine metabolism in the placenta and the unique metabolism of serine and glycine in the fetus. Dietary protein restriction in animals and marginal protein intake in humans causes characteristic changes in one carbon metabolism. The impact of perturbations in one carbon metabolism on the health of the mother during pregnancy, on fetal growth and the neonate are discussed and their possible mechanism explored.

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“…In contrast to SAM and S-adenosylhomocysteine, the remaining two members of SAM cycle -homocysteine (Tsitsiou et al 2009) and methionine (Bröer 2008) -can be transported through the plasma membrane by specific transporters. Therefore, increased serum concentration of homocysteine might in addition to inherited genetic diseases also reflect either increased rate of SAM utilization followed by an insufficient regeneration of methionine from homocysteine, or suppressed conversion of homocysteine to cysteine.…”

Section: S-adenosylmethionine Metabolismmentioning

confidence: 99%

Role of S-adenosylmethionine cycle in carcinogenesis

Murín¹,

Vidomanová²,

Kowtharapu³

et al. 2017

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Abstract. Alterations in enzymatic activities underlying the cellular capacity to maintain functional S-adenosylmethionine (SAM) cycle are associated with modified levels of its constituents. Since SAM is the most prominent donor of methyl group for sustaining the methylation pattern of macromolecules by methyltransferases, its availability is an essential prerequisite for sustaining the methylation pattern of nucleic acids and proteins. In addition, increased intracellular concentrations of S-adenosylhomocysteine and homocysteine, another two constituents of SAM cycle, exerts an inhibitory effect on the enzymatic activity of methyltranferases. While methylation pattern of DNA and histones is considered as an important regulatory hallmark in epigenetically regulated gene expression, amended methylation of several cellular proteins, including transcription factors, affects their activity and stability. Indeed, varied DNA methylome is a common consequence of disturbed SAM cycle and is linked with molecular changes underlying the transformation of the cells that may underlay the carcinogenesis. Here we summarize the recent evidences about the impact of disturbed SAM cycle on carcinogenesis.

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Homocysteine transport by systems L, A and y⁺L across the microvillous plasma membrane of human placenta

Cited by 35 publications

References 59 publications

Human Placental Arterial Distensibility, Birth Weight, and Body Size Are Positively Related to Fetal Homocysteine Concentration

Human Placental Arterial Distensibility, Birth Weight, and Body Size Are Positively Related to Fetal Homocysteine Concentration

One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health

Role of S-adenosylmethionine cycle in carcinogenesis

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Homocysteine transport by systems L, A and y+L across the microvillous plasma membrane of human placenta

Cited by 35 publications

References 59 publications

Human Placental Arterial Distensibility, Birth Weight, and Body Size Are Positively Related to Fetal Homocysteine Concentration

Human Placental Arterial Distensibility, Birth Weight, and Body Size Are Positively Related to Fetal Homocysteine Concentration

One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health

Role of S-adenosylmethionine cycle in carcinogenesis

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Homocysteine transport by systems L, A and y⁺L across the microvillous plasma membrane of human placenta