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-Menten kinetics with a Michaelis constant of 21.1 microM and the tested compounds were all suggested to inhibit it competitively with the values of the inhibition constant (K(i)) in the increasing order as follows: monobutyrin (41.0 microM)< or =monoacetin (54.6 microM)<diglycerol (154 microM)<1,2-propanediol (1650 microM). 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 (K(i)=484 microM) has a higher affinity than its R-(-)-enantiomer (K(i)=19100 microM), 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.
Fujimoto
Nami
N
Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
Inoue
Katsuhisa
K
Hayashi
Yayoi
Y
Yuasa
Hiroaki
H
D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D005990:Glycerol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D002352:Carrier Proteins; D005990:Glycerol