Page 256 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Abnormalities of Lipoprotein Metabolism
Among the disorders of fat metabolism there this process and ApoE is exposed. This leaves
are, in addition to the lipidoses (→ p. 244), VLDL remnants or intermediate density LP
mainly those diseases in which the concentra- (IDL), half of which return to the liver (binding
tions of lipoproteins in serum and thus lipid mostly with ApoE to the LDL receptors). They
transport in blood are abnormal. Lipids are are freshly loaded with lipids in the liver, leav-
transported in blood in globular molecular ing the liver as VLDL (→ A4). The other half of
complexes (microemulsions), the lipoproteins the IDL is transformed (with loss of ApoE and
(LPs). Their surface consists largely of amphi- exposure of ApoB 100 ) on contact with hepatic
philic lipids (phospholipids and nonesterified lipase to low density LP (LDL). Two thirds of
cholesterol), while their “core” contains non- these LDLs deliver their cholesterol and Chol-
polar (hydrophobic) lipids, i.e., triglycerides E to the liver (→ A7), one third to extrahepatic
(TGs) and cholesterol ester (Chol-E), the trans- tissues (→ A14), both processes requiring the
port and storage form of cholesterol. The LPs binding of ApoB 100 to the LDL receptors. By
also contain certain apolipoproteins (Apos). binding to receptors, mediated by clathrin in
The LPs differ in the size, density (which gives the coated pit regions of the cell surface, LDLs
them their name, see below), lipid composi-
undergo endocytosis in which the LDL recep-
Metabolism tion, site of origin as well as their apo(lipo)pro- tors recirculate to the cell membrane. After fu-
teins (see Table), the latter serving as structural
sion of the endosomes with lysosomes, the
apolipoproteins are “digested” and the Chol-E
elements of the LP (e.g., ApoAII and ApoB 48 ), as
sol (→ A5). As a result of this rise in the concen-
tors in the membrane of the LP target cells,
8 ligands (e.g., ApoB 100 and ApoE) for LP recep- split, so that free cholesterol reaches the cyto-
and as enzyme activators (e.g., ApoAI, ApoCII). tration of intracellular cholesterol: 1) the key
The chylomicrons transport lipids from the enzyme of cholesterol synthesis is inhibited
gut (via the gut lymphatics) to the periphery (3-HMG-CoA reductase); 2) cholesterol is again
(skeletal musculature, fat tissue), where their esterified to its storage form (activation of
ApoCII activates the endothelial lipoprotein li- acyl-CoA-cholesterol-acyl transferase [ACAT]);
pase (LPL); thus free fatty acids (FFAs) are split and 3) LDL receptor synthesis is inhibited.
off which are taken up by the cells of the mus- The high density LPs (HDLs) exchange cer-
cles and fat tissue (→ A2). In the liver the chy- tain apolipoproteins with chylomicrons and
lomicron remnants bind to receptors (LDL re- VLDLs and also take up excess cholesterol
ceptor–related protein [LRP]?) (→ A9) via from extrahepatic cells (→ A10) and blood.
ApoE, they are endocytosed and in this way de- By means of their ApoAI they activate the
liver their TGs as well as their cholesterol and plasma enzyme lecithin-cholesterol acyltrans-
cholesterol esters. Such imported as well as ferase ([LCAT] which in part esterifies the cho-
newly synthesized TG and cholesterol are ex- lesterol) and pass on cholesterol and Chol-E to
ported by the liver (→ A4) in very low density the liver, among other organs, and to those
LP (VLDL) to the periphery, where they activate steroid hormone–producing glands (ovaries,
LPL with their ApoCII, also leading to the re- testicles, adrenals) which have HDL receptors
lease of fatty acids (→ A3). ApoCII is lost in (→ A6).

Lipoprotein- % of Apolipoproteins Formations in Transport function
class* TG ChoL or [from]
Chylomicr. 90 3 AI, B 48 , CII + III, E Gut TG etc.: Gut ⇒ Periphery
Chyl. remnants [Chylomicr.] Lipids: Gut ⇒ Liver
VLDL 65 15 B 100 , CII + III, E Liver TG etc.: Liver ⇒ Periphery
IDL B 100 , CIII, E [VLDL,HDL] Lipids: ⇒ Liver, LDL
LDL 10 45 B 100 [IDL] Cholesterol: IDL ⇒ Liver, Periphery
246 HDL 5 20 AI,III + IV, CIII, D Periphery Cholesterol: Periphery ⇒ IDL
* Electrophoretic separation distinguishes between α-lipoproteins (= HDL), pre-β-lipoproteins (= VLDL) and β-lipoproteins (= LDL).
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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