Apolipoprotein B

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Apolipoprotein B (APOB) is the primary apolipoprotein of low density lipoproteins (LDL or "bad cholesterol"), and is responsible for carrying cholesterol to tissues. While it is unclear exactly what functional role APOB plays in LDL, it is the primary component and is absolutely required for its formation. Through a mechanism that is not fully understood, high levels of APOB can lead to plaques that cause heart disease (atherosclerosis). It is considered by many to be a better indicator of heart disease risk than total cholesterol or LDL.

1 Genetic disorders
2 Mouse studies
3 Molecular biology
4 References

[edit] Genetic disorders

High levels of APOB are related to heart disease. While there does appear to be a genetic component, the environmental component (what you eat) is a significant factor that should not be ignored.

Hypobetalipoproteinemia is a genetic disorder that can be caused by a mutation in the APOB gene, APOB, although it is usually caused by a mutation in the MTP gene, MTP.

[edit] Mouse studies

Most relevant information regarding mouse APOB homologue, mApoB, has come from mouse studies. Mice overexpressing mApoB have increased levels of LDL "bad cholesterol" and decreased levels of HDL "good cholesterol" ^[1]. Mice containing only one functional copy of the mApoB gene show the opposite effect, being resistant to hypercholesterolemia. Mice containing no functional copies of the gene are not viable ^[2].

[edit] Molecular biology

The protein occurs in the plasma in 2 main isoforms, APOB48 and APOB100. The first is synthesized exclusively by the small intestine, the second by the liver. Both isoforms are coded by APOB and by a single mRNA transcript larger than 16 kb. APOB48 is generated when a stop codon (UAA) at residue 2153 is created by RNA editing. There appears to be a trans-acting tissue-specific splicing gene that determines which isoform is ultimately produced. Alternatively, there is some evidence that a cis-acting element several thousand bp upstream determines which isoform is produced.

As a result of the RNA editing, APOB48 and APOB100 share a common N-terminal sequence, but APOB48 lacks APOB100's C-terminal LDL-receptor binding region.

[edit] References

^a Transgenic mice that overexpress mouse apolipoprotein B. Evidence that the DNA sequences controlling intestinal expression of the apolipoprotein B gene are distant from the structural gene. J Biol Chem. 1996 May 17; 271(20): 11963-70; PubMed Free text
^a Knockout of the Mouse Apolipoprotein B Gene Results in Embryonic Lethality in Homozygotes and Protection Against Diet-Induced Hypercholesterolemia in Heterozygotes. Proc Natl Acad Sci USA. 1995 Feb 28; 92(5): 1774-8; PubMed Free text