Very-low-density lipoprotein assembly and secretion
Abstract
The assembly of apolipoprotein B (apoB) into VLDL is broadly divided into two steps. The first involves transfer of lipid by the microsomal triglyceride transfer protein (MTP) to apoB during translation. The second involves fusion of apoB-containing precursor particles with triglyceride droplets to form mature VLDL. ApoB and MTP are homologs of the egg yolk storage protein, lipovitellin. Homodimerization surfaces in lipovitellin are reutilized in apoB and MTP to achieve apoB-MTP interactions necessary for first step assembly. Structural modeling predicts a small lipovitellin-like lipid binding cavity in MTP and a transient lipovitellin-like cavity in apoB important for nucleation of lipid sequestration. The formation of triglyceride droplets in the endoplasmic reticulum requires MTP however, their fusion with apoB may be MTP-independent. Second step assembly is modulated by phospholipase D and A2. Phospholipases may prime membrane transport steps required for second step fusion and/or channel phospholipids into a pathway for VLDL triglyceride production. The enzymology of VLDL triglyceride synthesis is still poorly understood; however, it appears that ACAT2 is the sole source of cholesterol esters for VLDL and chylomicron assembly. VLDL production is controlled primarily at the level of presecretory degradation. Recently, it was discovered that the LDL receptor modulates VLDL production through its interactions with nascent VLDL in the secretory pathway.
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About 95% of apoB binds to LDL particles, and each LDL particle binds to only one apoB molecule.
“About 95% of apoB binds to LDL particles, and each LDL particle binds to only one apoB molecule [42].”
From Effects of aerobic exercise on lipids and lipoproteins (2017) · cites this paper as [42]
ApoB is a major component of LDL particles and is essential for the removal of LDL particles in the circulation.
“ApoB is a major component of LDL particles and is essential for the removal of LDL particles in the circulation.”
From Effects of aerobic exercise on lipids and lipoproteins (2017) · cites this paper as [42]
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- Authors
- Shelness, G. S., & Sellers, J. A.
- Affiliations
- Wake Forest University Health Sciences (US)
- Corresponding author
- Shelness, Gregory S.
- Venue
- Current Opinion in Lipidology
- Published
- 2001-04
- Volume
- 12
- Issue
- 2
- Pages
- 151-157
- ISSN
- 0957-9672 (ISSN-L)
- OpenAlex
- W1993281511
- Cited by
- 309
- References
- 66
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 9 · 2023: 11 · 2022: 7 · 2021: 9 · 2020: 16 · 2019: 3 · 2018: 12 · 2017: 14 · 2016: 7 · 2015: 6 · 2014: 10 · 2013: 9 · 2012: 13
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Lipidology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 49373, P01HL049373)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- very low density lipoprotein assembly, apolipoprotein B, microsomal triglyceride transfer protein, lipovitellin, VLDL secretion, phospholipase D, phospholipase A2, ACAT2, cholesteryl ester synthesis, LDL receptor, chylomicron assembly, endoplasmic reticulum, lipoprotein secretion
- MeSH terms
- Animals, Apolipoproteins B, Carrier Proteins, Humans, Lipoproteins, VLDL, Phospholipases, Receptors, LDL, Triglycerides, Vitellogenins
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