Very low density lipoprotein apolipoprotein B metabolism in humans |
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Authors: | Th Demant J Shepherd C J Packard |
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Institution: | (1) University Department of Pathological Biochemistry, Royal Infirmary, Glasgow |
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Abstract: | Summary The human plasma lipoproteins encompass a broad spectrum of particles of widely varying physical and chemical properties whose metabolism is directed by their protein components. Apolipoprotein B100 (apo B100) is the major structural protein resident in particles within the Svedberg flotation range 0–400. The largest of these, the very low density lipoprotein (VLDL), rich in triglyceride, are metabolised by sequential delipidation through a transient intermediate density lipoprotein (IDL) to cholesterol-rich low density lipoproteins (LDL). Several components contribute to the regulation of this process, including (a) the lipolytic enzymes lipoprotein lipase and hepatic lipase (b), apolipoproteins B, CII, CIII and E, and (c) the apolipoprotein B/E or LDL receptor. Lipoprotein lipase acts primarily on large VLDL of Sf 60–400. Hepatic lipase on the other hand seems to be critical for the conversion of smaller particles (Sf 12–60) to LDL (Sf 0–12). Although most apo B100 flux is directed to the production of the delipidation end product LDL, along the length of the cascade there is potential for direct removal of particles from the system, probably via the actions of cell membrane receptors. This alternative pathway is particularly evident in hypertriglyceridaemic subjects, in whom the delipidation process is retarded.VLDL metabolism shows inter subject variability even in normal individuals. In this regard, apolipoprotein E plays an important role. Normolipidaemic individuals homozygous for the apo E2 variant exhibit gross disturbances in the transit of B protein through the VLDL-IDL-LDL chain.Abbreviations apo B, C, E
Apolipoprotein B, C, E
- CETP
Cholesteryl ester transfer protein
- FCH
Familial combined hyperlipidaemia
- FH
Familial hypercholesterolaemia
- FHTG
Familial hypertriglyceridaemia
- HDL
High density lipoprotein
- HL
Hepatic lipase
- IDL
Intermediate density lipoprotein
- LDL
Low density lipoprotein
- LpL
Lipoprotein lipase
- RFLP
Restriction fragment length polymorphism
- Sf
Svedberg flotation coefficient
- VLDL
Very low density lipoprotein
- WHHL
Watanabe heritable hyperlipidemic |
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Keywords: | VLDL-LDL conversion in normal and hyperlipoproteinaemic subjects Multicompartmental modelling Metabolic channelling |
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