Research progress on ATP citrate lyase (ACLY) inhibitors for decreasing blood lipids / 药学学报

Cardiovascular disease is a principal cause of morbidity and death in the world. Although drug therapy has made great progress in the past few decades, there are still many deficiencies in the prevention and treatment of cardiovascular disease. Dyslipidemia is still a common risk feature and is not sufficiently controlled. A growing body of evidence suggests that the occurrence and development of cardiovascular disease is associated with many associated risk factors, such as higher low-density lipoprotein levels, lower high-density lipoprotein levels and high triglyceride levels. A number of clinical trials in patients with dyslipidemia have shown that actively decreasing low density lipoprotein cholesterol can significantly decrease cardiovascular events. ATP citrate lyase (ACLY) is a cytoplasmic homo-tetrameric enzyme. In the presence of adenosine triphosphate (ATP), ACLY catalyzes the conversion of citric acid and coenzyme A to acetyl-CoA and oxalyl acetate. ACLY is the main enzyme for the production of cytoplasmic acetyl-CoA, and cytoplasmic acetyl-CoA is the precursor required for de novo synthesis of cholesterol and fatty acids. Therefore, it is possible to reduce the production of acetyl-CoA and reduce the levels of cholesterol and triglycerides by inhibiting ACLY. ACLY can be used as a molecular target for reducing blood lipids, and there are an increasing number of studies on ACLY inhibitors. In this paper, the structure and mechanism of ACLY and its relationship with lipid metabolism are briefly introduced, and we review some current ACLY inhibitors.

Cloning and sequence analysis of the full-length cDNA of a novel yp05 gene associated with citrinin production in Monascus aurantiacus / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To obtain the full-length cDNA of a novel gene (named yp05) associated with citrinin production-related genes in Monascus aurantiacus.</p><p><b>METHODS</b>Total RNA was extracted from mycelium, 3' and 5' cDNA end of yp05 gene was amplified using smart trace cDNA amplification kit, and the full-length cDNA of a novel gene (named yp05) was obtained from the electronic assembly of 3'-RACE and 5'-RACE products.</p><p><b>RESULTS</b>This yp05 gene was 787 bp including a 597 bp open reading frame (ORF) and encoded a deduced protein with 199 amino acid residues, and the amino acid sequence of this protein was found similar with the sequences of many fungal manganese-superoxide dismutases in the GenBank with the aid of BLASTp. The transcription of yp05 gene in Monascus strains was analyzed with the aid of Northern blotting. The transcription of yp05 gene was only detected in Monascus strains, provided that citrinin was produced.</p><p><b>CONCLUSION</b>The transcription of yp05 gene belongs to differential expression genes of citrinin yielded from Monascus and has no correlation with the biosynthesis pathway of red pigments.</p>

Serial analysis of gene expression in Monascus aurantiacus producing citrinin / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To construct a tag expression library of Monascus aurantiacus that could produce citrinin maximally on the thirteenth (0.966 mg/mL) day in the submerged culture.</p><p><b>METHODS</b>Total RNA was extracted from the mycelium, cDNA was synthesized using the SuperScript choice system, and then, a SAGE library was successfully constructed according to the MicroSAGE method.</p><p><b>RESULTS</b>Five hundred and ninety eight clones were obtained in SAGE library, and 120 clones were picked out randomly for identification and sequencing purpose. Eighty nine clones had positive inserts, 26 clones had no inserts and the remaining 5 clones had no site of NlaIII enzyme in inserts. There were seven repeated clones.</p><p><b>CONCLUSION</b>With the aid of SAGE2000 software, 901 tags were obtained from 89 clones, representing 686 unique transcripts. Six unique tags of them belong to highly expressed genes (Number of tags > or = 10) and 143 unique tags to moderately expressed genes (repeat tags > or = 2).</p>