EC Number   |
General Information |
Reference |
|---|
   6.2.1.16 | malfunction |
knockdown of AACS inhibits differentiation of 3T3-L1 cells and suppresses expression of the adipocyte markers, peroxisome proliferator-activated receptor gamma and CCAAT/enhancer binding protein alpha |
727116 |
| 6.2.1.16 | malfunction |
knockdown of SREBP-2, which orchestrates cholesterol synthesis, results in the downregulation of AACS mRNA levels. Knockdown of AACS results in a decrease in histone deacetylase 9, associated with gene silencing |
744249 |
| 6.2.1.16 | malfunction |
overexpression of recombinant mutants N500Q, N503Q, or N547Q, as well as of the wild-type enzyme, increases the ketone body-utilizing activity of HEK-293 cells, but that of N545Q does not. Overexpression of wild-type AACS, N500Q, or N503Q has no effect on legumain activity, but mutations N545Q and N547Q significantly reduce the activity compared to wild-type |
744906 |
| 6.2.1.16 | metabolism |
AACS is involved in the pathway of ketone body metabolism, overview |
-, 720477 |
| 6.2.1.16 | metabolism |
acetoacetyl-CoA synthetase (AACS) is responsible for the synthesis of cholesterol and fatty acids. It is cleaved by legumain, a lysosomal asparaginyl endopeptidase. Asn547 is the specific cleavage site of AACS in mouse livers. The cleaved form of AACS (1-547) loses the ability to convert acetoacetate to acetoacetyl-CoA. Overexpression of the cleaved form of AACS (1-547) increases the protein expression of caveolin-1, the principal component of the caveolae. Cleavage of AACS by legumain is critical for the regulation of enzymatic activity and results in gain-of-function changes |
744906 |
| 6.2.1.16 | metabolism |
Legumain is involved in the cleavage of AACS in the kidney, suggesting that AACS is degraded by the lysosomal pathway |
-, 744226 |
| 6.2.1.16 | more |
in addition to the two catalytic states, additional conformations are observed crystallographically that likely play a role in allowing access and egress of substrates and products from the relatively buried active site. The enzyme shows conformational flexibility. Structure-function analysis, overview. The C-terminal domain undergoes a large conformational change in the catalytic mechanism of acyl-CoA synthetases, the C-terminal extension is important for catalytic activity, structure comparisons. One region from the N-terminal domain interacts is the so-called P-loop, a glycine-, serine-, and threonine-rich region that interacts with the phosphates of ATP. This P-loop adopts multiple conformations in the different crystal structures and may play an important role in the release of PPi and trigger the conformational change. Specifically, the main chain carbonyls of Ser272, Gly274, and Gly277 form direct or water-mediated hydrogen bonds with Asn637 and Ser640. Asn637 also interacts directly with Arg183 and Asp187, while the carbonyl of Gly639 and the carbonyl and side chain oxygens of Ser640 interact with Ser184, Asp187, and Arg188. |
-, 746014 |
| 6.2.1.16 | more |
site-specific cleavage at residue Asn547 of acetoacetyl-CoA synthetase by legumain, a lysosomal asparaginyl endopeptidase. The cleaved form of AACS (1-547) loses the ability to convert acetoacetate to acetoacetyl-CoA |
744906 |
| 6.2.1.16 | more |
transcription mechanism of AACS, expression of AACS is regulated by cholesterol depletion, overview |
-, 720477 |
| 6.2.1.16 | physiological function |
AACS plays an important role in cholesterol homeostasis |
-, 720477 |
