Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
K L WiddowsJ D Glazier

Abstract

Uptake of system L amino acid substrates into isolated placental plasma membrane vesicles in the absence of opposing side amino acid (zero-trans uptake) is incompatible with the concept of obligatory exchange, where influx of amino acid is coupled to efflux. We therefore hypothesized that system L amino acid exchange transporters are not fully obligatory and/or that amino acids are initially present inside the vesicles. To address this, we combined computational modeling with vesicle transport assays and transporter localization studies to investigate the mechanisms mediating [(14)C]L-serine (a system L substrate) transport into human placental microvillous plasma membrane (MVM) vesicles. The carrier model provided a quantitative framework to test the 2 hypotheses that l-serine transport occurs by either obligate exchange or nonobligate exchange coupled with facilitated transport (mixed transport model). The computational model could only account for experimental [(14)C]L-serine uptake data when the transporter was not exclusively in exchange mode, best described by the mixed transport model. MVM vesicle isolates contained endogenous amino acids allowing for potential contribution to zero-trans uptake. Both L-type amino acid tr...Continue Reading

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Citations

Apr 6, 2016·Biochimica Et Biophysica Acta·N PanitchobB G Sengers
Jul 28, 2016·Expert Opinion on Drug Delivery·Abhirup MandalAshim K Mitra
May 10, 2017·The Journal of Endocrinology·Colin P Sibley
Jul 10, 2018·The Journal of Physiology·Jane K ClealRohan M Lewis
Aug 5, 2020·Journal of Developmental Origins of Health and Disease·Yutthapong Tongpob, Caitlin Wyrwoll
Dec 18, 2015·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·E M LofthouseR M Lewis
Jun 18, 2020·Nutrients·Chien-Ning Hsu, You-Lin Tain
Feb 20, 2021·Neurochemical Research·Ekaitz Errasti-Murugarren, Manuel Palacín
May 9, 2021·The Journal of Nutritional Biochemistry·Jonas ZauggChristiane Albrecht
Aug 19, 2021·Clinical Science·Owen R VaughanThomas Jansson

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Methods Mentioned

BETA
amino acid exchange

Software Mentioned

GraphPad
MATLAB
GraphPad Prism

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