Key result
L-homoarginine is a substrate of CAT1, CAT2A, and CAT2B, with cellular uptake significantly higher in CAT1-overexpressing cells (7-fold) compared to controls.
Effect estimate: 7-fold
Absolute Event Rate: 7% vs 1%
p-value: p=<0.001
L-homoarginine is a substrate of CAT1, CAT2A, and CAT2B, with CAT1 being a key site for its cellular uptake and physiological interactions with L-arginine.
Animal data on CAT-mediated uptake leave open L-homoarginine's role in human cardiovascular physiology; human studies required.
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 K M -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.
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Chafai et al. (2017) studied this question. L-homoarginine vs. Control cells (HEK VCG418 or HEK VCHygro) was evaluated on Cellular uptake of L-homoarginine (fold increase vs control for CAT1) (7-fold, p=<0.001). L-homoarginine is a substrate of CAT1, CAT2A, and CAT2B, with cellular uptake significantly higher in CAT1-overexpressing cells (7-fold) compared to controls.
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