it showed that overexpression of human ACAT 1 in mice leads to increased production of increased and VLDL liver cholesterol ester levels, but no change in liver cholesterol levels. Overexpression of human ACAT 1 in hamsters did not alter expression of the LDLr. At first sight, this differs from our findings that an increase in SER cholesterol ester was associated with reduced expression of the LDLr. However, changes in bulk liver cholesterol ester may well not always re ect changes in the very little p53 ubiquitination membrane pool. Furthermore, there are two kinds of ACAT: ACAT 1, which is ubiquitous, and ACAT 2, which is found in liver and intestine. It’s been proposed that ACAT 1 might provide cholesterol esters for storage, whereas cholesterol esters are produced by ACAT 2 for secretion in VLDL. Complete cellular cholesterol levels are signalled for the SREBP SCAPS1P. The signal required have to be stated in proportion for the cholesterol load and be readily inactivated or eliminated, when cholesterol levels fall, to ensure signalling is stopped. Cholesterol is transferred to the ER and esterified, thus ER Mitochondrion cholesterol ester is an indicator of cholesterol loading, when mobile cholesterol levels increase. Moreover, the membrane cholesterol ester pool is very small compared with membrane cholesterol and is taken off the membrane to cytosolic stores or for secretion as a factor of VLDL. Thus ER cholesterol ester better suits the part of a signalling molecule than unesterified cholesterol and alters in parallel with modification of gene expression and changes in SREBP 2 localization. We can not exclude the possibility that a tiny part of the membrane unesterified cholesterol is regulatory and that the cholesterol ester levels re ect inactivation of this pool However, the method employed for lipid analysis is very sensitive and unmasked variations in membrane unesterified cholesterol ester levels, which are far smaller compared to the membrane cholesterol pool. It is also possible that changes in ER membrane unesterified cholesterol levels are masked by contamination with plasma membrane Cathepsin Inhibitor 1 vesicles, which are highly enriched in cholesterol. Nevertheless, plasma membrane vesicles and caveolae would move to the top of the gradient used and, although they may subscribe to the complete microsome unesterified cholesterol, they’d not contaminate the ER gradient fractions. The process by which SER membrane cholesterol ester may modulate transfer of SCAPSREBP to the S1P containing area is not known. The ER can be a continuous membrane, however, transfer from your SER to the cis Golgi network involves vesicle formation and membrane future has been implicated in SREPBSCAP transfer. A role for cholesterol ester in vesicle development, through changes in the actual construction of the bilayer and in employment of SCAP into vesicles budding from the SER, is possible but requires further investigation.