Homeostasis of free cholesterol in the blood: a preliminary evaluation and modeling of its passive transport.
The rate of noncatalyzed transfer of cholesterol (Chol) among lipoproteins and cells in the blood is of fundamental importance as a baseline to assess the role of active transport mechanisms, but remains unknown. Here we address this gap by characterizing the associa-tion of the Chol analog, ergosta-5,7,9(11),22-tetraen-3β-ol (DHE), with the lipoproteins VLDL, LDL, HDL2, and HDL3 Combining these results with data for the association of DHE with liposomes, we elaborated a kinetic model for the noncatalyzed exchange of free Chol among blood compartments. The computational results are in good agreement with experimental values. The small deviations are explained by the nonequilibrium distribution of unesterified Chol in vivo, due to esterification and entry of new unesterified Chol, and eventual effects introduced by incubations at low temperatures. The kinetic profile of the homeostasis of unesterified Chol in the blood predicted by the model developed in this work is in good agreement with the observations in vivo, highlighting the importance of passive processes.
Departamento de Química, Universidade de Coimbra, Coimbra, Portugal CNC - Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal.
Luís M B B
LM
Estronca
Departamento de Química, Universidade de Coimbra, Coimbra, Portugal Centro de Química de Coimbra, Universidade de Coimbra, Coimbra, Portugal.
Hugo A L
HA
Filipe
Departamento de Química, Universidade de Coimbra, Coimbra, Portugal CNC - Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal.
Armindo
A
Salvador
Departamento de Química, Universidade de Coimbra, Coimbra, Portugal Centro de Química de Coimbra, Universidade de Coimbra, Coimbra, Portugal.
Maria João
MJ
Moreno
Departamento de Química, Universidade de Coimbra, Coimbra, Portugal Centro de Química de Coimbra, Universidade de Coimbra, Coimbra, Portugal.
Winchil L C
WL
Vaz
D000328:Adult; D001692:Biological Transport / Q000502:physiology; D002784:Cholesterol / Q000097:blood*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis*; D008297:Male
D008074:Lipoproteins; D002784:Cholesterol
cholesterol homeostasis; dehydroergosterol; high density lipoprotein; lipoproteins; low density lipoprotein