Acyl-coenzyme A:cholesterol acyltransferase (ACAT) catalyzes the esterification of cholesterol with long chain fatty acids. Northern blot analysis and RNase protection assays of mouse tissues revealed that ACAT mRNA is expressed most highly in the adrenal gland, ovary, and preputial gland and is least abundant in skeletal muscle, adipose tissue, heart, and brain (Uelmen et al. 1995 ).
NCBI Summary:
The protein encoded by this gene belongs to the acyltransferase family. It is located in the endoplasmic reticulum, and catalyzes the formation of fatty acid-cholesterol esters. This gene has been implicated in the formation of beta-amyloid and atherosclerotic plaques by controlling the equilibrium between free cholesterol and cytoplasmic cholesteryl esters. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2011]
General function
Metabolism, Enzyme, Transferase
Comment
Cellular localization
microsome
Comment
Ovarian function
Steroid metabolism
Comment
Expression regulated by
LH, Steroids
Comment
Schuler et al., 1981 concluded that HMG-CoA reductase and ACAT are regulated, in a reciprocal fashion, by ovarian cholesterol balance. When sufficient cholesterol is available, HMG-CoA reductase is suppressed and ACATincreases to facilitate esterification of sterol in excess of cell needs. When exogenous sterol supplies cannot meet ovarian demands,HMG-CoA reductase rises, and there is a concomitant decline in ACAT. Thus, gonadotropic control over these enzymes may be exerted, in part, through modulation of the supply of cholesterol to the ovary and/or through regulation of the rate of sterol utilization forhormone synthesis.
Ovarian localization
Oocyte, Granulosa
Comment
This gene was found in a rat ovarian cDNA library (Unigene).
Taft RA, et al 2002 reported the identification of genes encoding mouse oocyte secretory and
transmembrane proteins by a signal sequence trap.///////Protein Lysine Acetylation in Ovarian Granulosa Cells Affects Metabolic Homeostasis and Clinical Presentations of Women With Polycystic Ovary Syndrome. Min Z et al. (2020) Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders accompanied by obvious metabolic abnormalities. Lower-quality oocytes and embryos are often found in PCOS women during assisted reproductive technology treatment. However, there is still no clarity about the mechanism of ovarian metabolic disorders and the impact on oocyte maturation in PCOS. The aim of this study was to understand the potential effect of the posttranslational modification on ovarian metabolic homeostasis and oocyte development potential in women with PCOS. A quantitative analysis of acetylated proteomics in ovarian granulosa cells of PCOS and control groups was carried out by mass spectrometry. There was widespread lysine acetylation of proteins, of which 265 proteins had increased levels of acetylation and 68 proteins had decreased levels of acetylation in the PCOS group. Most notably, differentially acetylated proteins were significantly enriched in the metabolic pathways of glycolysis, fatty acid degradation, TCA cycle, tryptophan metabolism, and branched-chain amino acid degradation. Acetyl-CoA acetyltransferase 1 (ACAT1) was an enzyme central to these metabolic pathways with increased acetylation level in the PCOS group, and there was a negative correlation of ACAT1 acetylation levels in PCOS granulosa cells with oocyte quality and embryo development efficiency in the clinic. Lysine acetylation changes of key enzymes in PCOS granulosa cells might attenuate their activities and alter metabolic homeostasis of follicular microenvironment for oocyte maturation and embryo development.//////////////////
At all stages of follicular
development, oocytes interact with surrounding granulosa cells and promote their
differentiation into the types of cells that support further oocyte growth and
developmental competence. These interactions suggest the existence of an
oocyte-granulosa cell regulatory loop that includes both secreted proteins and cell
surface receptors on both cell types. Factors involved in the regulatory loop will
therefore contain a signal sequence, which can be used to identify them through a
signal sequence trap (SST). A screen of an oocyte SST library identified three
classes of oocyte-expressed sequences: known mouse genes, sequences homologous
to known mammalian genes, and novel sequences of unknown function. Many of the
recovered genes may have roles in the oocyte-granulosa cell regulatory loop. For
several of the known mouse genes, new roles in follicular development are implied
by identification of their expression, for the first time, in the oocyte.
ACYL-CoA:CHOLESTEROL ACYLTRANSFERASE was found by the SST screen.
Changes in mouse granulosa cell gene expression during early luteinization. McRae RS et al. Changes in gene expression during granulosa cell luteinization have been measured using serial analysis of gene expression (SAGE). Immature normal mice were treated with pregnant mare serum gonadotropin (PMSG) or PMSG followed, 48 h later, by human chorionic gonadotropin (hCG). Granulosa cells were collected from preovulatory follicles after PMSG injection or PMSG/hCG injection and SAGE libraries generated from the isolated mRNA. The combined libraries contained 105,224 tags representing 40,248 unique transcripts. Overall, 715 transcripts showed a significant difference in abundance between the two libraries of which 216 were significantly down-regulated by hCG and 499 were significantly up-regulated. Among transcripts differentially regulated, there were clear and expected changes in genes involved in steroidogenesis as well as clusters of genes involved in modeling of the extracellular matrix, regulation of the cytoskeleton and intra and intercellular signaling. The SAGE libraries described here provide a base for functional investigation of the regulation of granulosa cell luteinization.
Follicle stages
Corpus luteum
Comment
The corpus luteum of the rat stores large quantities of cholesteryl ester which is synthesized by acyl coenzyme A:cholesterol acyltransferase (ACAT). In the absence of exogenous cholesterol, ACAT activity in the PMSG-primed rat ovary increased between days 1-8 post-hCG treatment and then declined between days 8-15. When exogenous cholesterol was included, a similar pattern of ACAT activity was found, but rates of cholesteryl ester formation were 2.5- to 4.5-fold greater. Tavani et al., 1982 indicated that the entry of cholesterol into the ACAT substrate pool may be a major factor controlling the rates of cholesteryl ester synthesis in the rat corpus luteum.