The prognostic biomarker L-homoarginine is a substrate of the cationic amino acid transporters CAT1, CAT2A and CAT2B

Abstract Low plasma concentration of L-homoarginine is an independent predictor of cardiovascular events and total mortality. Experimental data indicate that supplementation of L-homoarginine may have protective effects. We aimed to elucidate the mechanisms involved in the cellular uptake of L-homoa...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Anja Chafai, Martin F. Fromm, Jörg König, Renke Maas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4d049ac98f054c6ba4f7aa0fe4a0e33b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4d049ac98f054c6ba4f7aa0fe4a0e33b
record_format	dspace
spelling	oai:doaj.org-article:4d049ac98f054c6ba4f7aa0fe4a0e33b2021-12-02T11:52:38ZThe prognostic biomarker L-homoarginine is a substrate of the cationic amino acid transporters CAT1, CAT2A and CAT2B10.1038/s41598-017-04965-22045-2322https://doaj.org/article/4d049ac98f054c6ba4f7aa0fe4a0e33b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04965-2https://doaj.org/toc/2045-2322Abstract Low plasma concentration of L-homoarginine is an independent predictor of cardiovascular events and total mortality. Experimental data indicate that supplementation of L-homoarginine may have protective effects. We aimed to elucidate the mechanisms involved in the cellular uptake of L-homoarginine, which are little understood, so far. Using human embryonic kidney (HEK293) cell lines stably overexpressing the human cationic amino acid transporters CAT1 [solute carrier family 7 (SLC7A1)], CAT2A (SLC7A2A) or CAT2B (SLC7A2B) we assessed the transport kinetics of L-homoarginine and interactions with the CAT substrates L-arginine and asymmetric dimethylarginine (ADMA). Significant uptake of L-homoarginine was observed for all three CATs with apparent KM-values of 175 ± 7 µM for CAT1 and 523 ± 35 µM for CAT2B. Saturation of CAT2A-mediated L-homoarginine uptake could not be reached. Uptake of L-homoarginine by any of the three CATs could be inhibited by L-arginine and ADMA. Significant inhibition of CAT1-mediated uptake of L-homoarginine by L-arginine already occurred in the physiological concentration range. Taken together these data demonstrate that L-homoarginine is a substrate of CAT1, CAT2A and CAT2B and that CAT1 is a key site with regard to physiological relevance and interactions with related substrates such as L-arginine.Anja ChafaiMartin F. FrommJörg KönigRenke MaasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anja Chafai Martin F. Fromm Jörg König Renke Maas The prognostic biomarker L-homoarginine is a substrate of the cationic amino acid transporters CAT1, CAT2A and CAT2B
description	Abstract Low plasma concentration of L-homoarginine is an independent predictor of cardiovascular events and total mortality. Experimental data indicate that supplementation of L-homoarginine may have protective effects. We aimed to elucidate the mechanisms involved in the cellular uptake of L-homoarginine, which are little understood, so far. Using human embryonic kidney (HEK293) cell lines stably overexpressing the human cationic amino acid transporters CAT1 [solute carrier family 7 (SLC7A1)], CAT2A (SLC7A2A) or CAT2B (SLC7A2B) we assessed the transport kinetics of L-homoarginine and interactions with the CAT substrates L-arginine and asymmetric dimethylarginine (ADMA). Significant uptake of L-homoarginine was observed for all three CATs with apparent KM-values of 175 ± 7 µM for CAT1 and 523 ± 35 µM for CAT2B. Saturation of CAT2A-mediated L-homoarginine uptake could not be reached. Uptake of L-homoarginine by any of the three CATs could be inhibited by L-arginine and ADMA. Significant inhibition of CAT1-mediated uptake of L-homoarginine by L-arginine already occurred in the physiological concentration range. Taken together these data demonstrate that L-homoarginine is a substrate of CAT1, CAT2A and CAT2B and that CAT1 is a key site with regard to physiological relevance and interactions with related substrates such as L-arginine.
format	article
author	Anja Chafai Martin F. Fromm Jörg König Renke Maas
author_facet	Anja Chafai Martin F. Fromm Jörg König Renke Maas
author_sort	Anja Chafai
title	The prognostic biomarker L-homoarginine is a substrate of the cationic amino acid transporters CAT1, CAT2A and CAT2B
title_short	The prognostic biomarker L-homoarginine is a substrate of the cationic amino acid transporters CAT1, CAT2A and CAT2B
title_full	The prognostic biomarker L-homoarginine is a substrate of the cationic amino acid transporters CAT1, CAT2A and CAT2B
title_fullStr	The prognostic biomarker L-homoarginine is a substrate of the cationic amino acid transporters CAT1, CAT2A and CAT2B
title_full_unstemmed	The prognostic biomarker L-homoarginine is a substrate of the cationic amino acid transporters CAT1, CAT2A and CAT2B
title_sort	prognostic biomarker l-homoarginine is a substrate of the cationic amino acid transporters cat1, cat2a and cat2b
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4d049ac98f054c6ba4f7aa0fe4a0e33b
work_keys_str_mv	AT anjachafai theprognosticbiomarkerlhomoarginineisasubstrateofthecationicaminoacidtransporterscat1cat2aandcat2b AT martinffromm theprognosticbiomarkerlhomoarginineisasubstrateofthecationicaminoacidtransporterscat1cat2aandcat2b AT jorgkonig theprognosticbiomarkerlhomoarginineisasubstrateofthecationicaminoacidtransporterscat1cat2aandcat2b AT renkemaas theprognosticbiomarkerlhomoarginineisasubstrateofthecationicaminoacidtransporterscat1cat2aandcat2b AT anjachafai prognosticbiomarkerlhomoarginineisasubstrateofthecationicaminoacidtransporterscat1cat2aandcat2b AT martinffromm prognosticbiomarkerlhomoarginineisasubstrateofthecationicaminoacidtransporterscat1cat2aandcat2b AT jorgkonig prognosticbiomarkerlhomoarginineisasubstrateofthecationicaminoacidtransporterscat1cat2aandcat2b AT renkemaas prognosticbiomarkerlhomoarginineisasubstrateofthecationicaminoacidtransporterscat1cat2aandcat2b
_version_	1718394982894665728

The prognostic biomarker L-homoarginine is a substrate of the cationic amino acid transporters CAT1, CAT2A and CAT2B

Ejemplares similares