Effect of Glycerol-Related Compounds on Carrier-Mediated Glycerol Uptake in HCT-15 Human Colon Cancer Cell Line

The effect of several compounds, which are structurally analogous to glycerol, on carrier-mediated glycerol uptake was examined in HCT-15 cells to help clarifying the functional characteristics of the glycerol transport system. The carrier-mediated uptake of glycerol conformed to the Michaelis-Mente...

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Bibliographic Details
Published in:DRUG METABOLISM AND PHARMACOKINETICS 2008-01, Vol.23 (3), p.216-220
Main Authors: Fujimoto, Nami, Inoue, Katsuhisa, Hayashi, Yayoi, Yuasa, Hiroaki
Format: Article
Language:English
Subjects:
Biological Transport, Active
Carrier Proteins - metabolism
Carrier Proteins - physiology
carrier-mediated transport
Cell Line, Tumor
Colonic Neoplasms
competitive inhibition
enantioselectivity
glycerol
Glycerol - analogs & derivatives
Glycerol - metabolism
Glycerol - pharmacology
HCT-15 cell
Humans
Stereoisomerism
Structure-Activity Relationship
Substrate Specificity
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Summary:The effect of several compounds, which are structurally analogous to glycerol, on carrier-mediated glycerol uptake was examined in HCT-15 cells to help clarifying the functional characteristics of the glycerol transport system. The carrier-mediated uptake of glycerol conformed to the Michaelis-Menten kinetics with a Michaelis constant of 21.1 μM and the tested compounds were all suggested to inhibit it competitively with the values of the inhibition constant (Ki) in the increasing order as follows: monobutyrin (41.0 μM) < monoacetin (54.6 μM) < diglycerol (154 μM) < 1,2-propanediol (1650 μM). Therefore, they all may possibly be substrates of the carrier-mediated glycerol transport system, for which the glycerol esters (monoacetin and monobutyrin) have the highest affinities among them. It was also found that S-( + )-enantiomer of 1,2-propanediol (Ki = 484 μM) has a higher affinity than its R-( – )-enantiomer (Ki=19100 μM), indicating enantioselective recognition. These results support the suggestion that a specific carrier protein is involved in glycerol uptake in HCT-15 cells. It would be of interest to identify the carrier, which may be present also in some organs, and further investigate the possibility that glycerol ester derivatives of drugs might be delivered via the carrier.
ISSN:1347-4367
1880-0920
DOI:10.2133/dmpk.23.216