Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatty acid biosynthesis is an emerging target for the development of novel antibacterial chemotherapeutics. The dissociated bacterial system is substantially different from the large, multifunctional protein of mammals, and many possibilities exist for type-selective drugs. Several compounds, both synthetic and natural, target bacterial fatty acid synthesis. Three compounds target the FabI enoyl-ACP reductase step; isoniazid, a clinically used antituberculosis drug, triclosan, a widely used consumer antimicrobial, and diazaborines. In addition, cerulenin and thiolactomycin, two fungal products, inhibit the FabH, FabB and FabF condensation enzymes. Finally, the synthetic reaction intermediates BP1 and decynoyl- N-acetyl cysteamine inhibit the acetyl-CoA carboxylase and dehydratase isomerase steps, respectively. The mechanisms of action of these compounds, as well as the potential development of new drugs targeted against this pathway, are discussed.
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PMID:Inhibitors of fatty acid synthesis as antimicrobial chemotherapeutics. 1202 87

New chemotherapies for human and animal apicomplexan infections are needed as a component of future strategies to deal with these diseases. An extensive search for new treatments exploring the unique developmental physiology, metabolism and molecular structures of Apicomplexa is under way. The description of the full complement of about 5,300 Plasmodium falciparum genes and fast growing sequence databases for other Apicomplexa allow reconstruction of metabolic pathways of these parasites and thus accelerate identification and biochemical analysis of potential targets. The apicoplast de novo fatty acid biosynthetic pathway shows great potential as a target for small-molecule inhibitors in a stand-alone or combination chemotherapy. Three enzymatic activities, acetyl-CoA carboxylase, beta-ketoacyl-ACP synthase and enoyl-ACP reductase, respond to inhibitors previously identified for bacteria and plants, and deserve to be explored in depth. In this connection, screening systems have been established to seek more potent and specific antiparasitic compounds that are harmless to the host. To this end the interconnections of fatty acid biosynthesis in Apicomplexa with other metabolic and cellular processes must be investigated.
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PMID:Apicoplast fatty acid biosynthesis as a target for medical intervention in apicomplexan parasites. 1290 73

For the first time, a genome-wide transcriptional analysis was performed to elucidate the cellular response of Staphylococcus aureus to triclosan. Our results indicate that the effects of triclosan are widespread on metabolism, affecting many vital cellular processes. Triclosan downregulated the transcription of genes involved in virulence factor and energy metabolism such as amino acid, carbohydrate, lipid transport, and metabolism, while multidrug resistance genes, coenzyme transport, and metabolism and transcription genes were upregulated. Furthermore, triclosan downregulated the transcription of genes encoding major lipid metabolism enzymes such as 3-hydroxyacyl-CoA dehydrogenase, acetyl-CoA acetyltransferase, acetyl-CoA synthetase, and acetyl-CoA carboxylase, which all play essential roles in S. aureus lipid metabolism. It is interesting to note that the expression of the enoyl-ACP reductase gene, fabI, was not changed after exposure of S. aureus with 0.05 microM triclosan at 10 and 60 min in our study. This work also implies that triclosan may kill S. aureus by interfering with its ability to form cell membranes. Another important implication of our result is that S. aureus may generate resistance factors under triclosan stress.
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PMID:Microarray analysis of toxicogenomic effects of triclosan on Staphylococcus aureus. 1821 Jan 2