Sterol O-acyltransferase

Source: Wikipedia, the free encyclopedia.
sterol O-acyltransferase
Identifiers
ExPASy
NiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
Chr. 1 q25
Search for
StructuresSwiss-model
DomainsInterPro
Chr. 12 [1]
Search for
StructuresSwiss-model
DomainsInterPro

Sterol O-acyltransferase (also called Acyl-CoA cholesterol acyltransferase, Acyl-CoA cholesterin acyltransferase[citation needed] or simply ACAT) is an intracellular protein located in the endoplasmic reticulum that forms cholesteryl esters from cholesterol.

Sterol O-acyltransferase catalyzes the chemical reaction:

acyl-CoA + cholesterol CoA + cholesterol ester

Thus, the two

substrates of this enzyme are acyl-CoA and cholesterol, whereas its two products are CoA and cholesteryl ester
.

This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups, the membrane-bound O-acyltransferases. This enzyme participates in bile acid biosynthesis.

Class and structure

Acyl-CoA cholesterol

acyltransferases. The role of this enzyme is to transfer fatty acyl groups from one molecule to another. ACAT is an important enzyme in bile acid biosynthesis
.

In nearly all mammalian cells, ACAT catalyzes the intracellular

macrophages and vascular tissue. The rate-controlling enzyme in cholesterol catabolism, hepatic cholesterol 7-hydroxylase, is believed to be regulated partly by ACAT.[1]

Mechanism

The mechanism scheme is as follows:
Acyl-CoA + Cholesterol ←→ CoA + Cholesteryl ester
[2]

Isoforms

There are two

pathologies associated with abnormalities in lipid metabolism.[3]

SOAT1 (ACAT1)

Previous studies have shown that SOAT modulates proteolytic processing in cell-based and animal models of

Abeta generation.[3]

SOAT2 (ACAT2)

In a recent study, it was shown that SOAT2 activity is upregulated as a result of chronic renal failure. This study was specific to hepatic SOAT, which plays a major role in hepatic production and release of very low density lipoprotein (

In another study, non-human primates revealed a positive correlation between liver cholesteryl ester secretion rate and the development of coronal artery atherosclerosis. The results of the experiment are indicative that under all of the conditions of cellular cholesterol availability tested, the relative level of SOAT2 expression affects the cholesteryl ester content, and therefore the atherogenecity of nascent apoB-containing lipoproteins.[4]

Yeast

In yeast, acyl-CoA:sterol acyltransferase (ASAT) is functionally equivalent to ACAT. Although studies in vitro and in yeast suggest that the acyl-CoA binding protein (ACBP) may modulate long-chain fatty acyl-CoA (LCFA-CoA) distribution, the physiological function in mammals is unresolved. Recent research suggests that ACBP expression may play a role in LCFA-CoA metabolism in a physiological context.[5]

In

sporulation efficiency.[6]

Plant Synthesis of Steryl Esters

In

plants cellular sterol ester synthesis is performed by an enzyme different from mammalian ACAT and yeast ASAT; it is performed by Phospholipid:Sterol Acyltransferase (PSAT). A recent study shows that PSAT is involved in the regulation of the pool of free sterols and the amount of free sterol intermediates in the membranes. It is also described as the only intracellular enzyme discovered that catalyzes an acyl-CoA independent sterol ester formation. PSAT is therefore considered to have a similar physiological function in plant cells as ACAT in animal cells.[7]

See also

  • ACAT1 mRNA
  • Lecithin—cholesterol acyltransferase
    (LCAT)

References

  1. PMID 11325614
    .
  2. ^ "KEGG Reaction: R01461". Kyoto Encyclopedia of Genes and Genomes. Kanehisa Laboratories. Retrieved 2009-05-06.
  3. ^
    PMID 17438337
    .
  4. .
  5. .
  6. .
  7. .

Further reading