TY - JOUR
T1 - Kinetic characteristics and mechanisms of regulation of receptor-dependent and receptor-independent LDL transport in the liver of different animal species and humans
AU - Meddings, Jonathan B.
AU - Spady, David K.
AU - Dietschy, John M.
N1 - Funding Information:
From the Gastroenterology Division, Department of Internal MBdicine, the University of Texas Wealth Science Center at Dallas, Southwestern Medical School. Supported by US Public Health Service Research Grants HL-09610 and AM-19329 and by a grant from the Moss Heart Fund. Reprint requests: John M. Dietschy, M.D., Department of Internal Medicine, University of Texas Health Science Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75235-9030.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1987/2
Y1 - 1987/2
N2 - In the normal animal and in humans, low-density lipoproteins (LDL) are removed from the plasma by both receptor-dependent and receptor-independent transport mechanisms. Most of the receptor-dependent transport activity is found in the liver, whereas the receptor-independent transport process is widely distributed in many organs. In the steady state the plasma LDL-cholesterol concentration is determined by the rate of LDL production, relative to the rate of LDL removal from the vascular space. This rate of removal in turn is determined by three transport parameters: Jm, the maximal transport rate for the receptor-dependent process in the whole animal; Km, the concentration of LDL-cholesterol in the plasma at which half Jm is achieved; and P, the proportionality constant for the receptor-independent transport process. The values of these parameters are now known for several species, including humans and provide the basis for understanding how the plasma LDL-cholesterol concentration is altered by environmental factors such as aging and diet. With aging, for example, there appears to be no change in the receptor-dependent transport process, and in those situations in which the plasma LDL-cholesterol level rises, this increase appears to be caused by overproduction of LDL. With cholesterol feeding the plasma LDL-cholesterol level rises because of an increase in the LDL production rate coupled with a decrease in the maximal transport rate for the receptor-dependent process. The addition of saturated triglycerides to the diet further suppresses the Jm value, whereas unsaturated lipids enhance the maximal transport rate for LDL and lowers the plasma LDL-cholesterol level. Thus with these transport data it is now possible to identify the mechanism whereby any dietary or pharmacologic manipulation alters plasma LDL-cholesterol concentrations.
AB - In the normal animal and in humans, low-density lipoproteins (LDL) are removed from the plasma by both receptor-dependent and receptor-independent transport mechanisms. Most of the receptor-dependent transport activity is found in the liver, whereas the receptor-independent transport process is widely distributed in many organs. In the steady state the plasma LDL-cholesterol concentration is determined by the rate of LDL production, relative to the rate of LDL removal from the vascular space. This rate of removal in turn is determined by three transport parameters: Jm, the maximal transport rate for the receptor-dependent process in the whole animal; Km, the concentration of LDL-cholesterol in the plasma at which half Jm is achieved; and P, the proportionality constant for the receptor-independent transport process. The values of these parameters are now known for several species, including humans and provide the basis for understanding how the plasma LDL-cholesterol concentration is altered by environmental factors such as aging and diet. With aging, for example, there appears to be no change in the receptor-dependent transport process, and in those situations in which the plasma LDL-cholesterol level rises, this increase appears to be caused by overproduction of LDL. With cholesterol feeding the plasma LDL-cholesterol level rises because of an increase in the LDL production rate coupled with a decrease in the maximal transport rate for the receptor-dependent process. The addition of saturated triglycerides to the diet further suppresses the Jm value, whereas unsaturated lipids enhance the maximal transport rate for LDL and lowers the plasma LDL-cholesterol level. Thus with these transport data it is now possible to identify the mechanism whereby any dietary or pharmacologic manipulation alters plasma LDL-cholesterol concentrations.
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U2 - 10.1016/0002-8703(87)90617-X
DO - 10.1016/0002-8703(87)90617-X
M3 - Article
C2 - 3812205
AN - SCOPUS:0023145159
VL - 113
SP - 475
EP - 481
JO - American Heart Journal
JF - American Heart Journal
SN - 0002-8703
IS - 2 PART 2
ER -