The importance of coenzyme A (CoA) as a carrier of acyl residues in cell metabolism is well understood. Coenzyme A participates in more than 100 different catabolic and anabolic reactions, including those involved in the metabolism of lipids, carbohydrates, proteins, ethanol, bile acids, and xenobiotics. However, much less is known about the importance of the concentration of this cofactor in various cell compartments and the role of altered CoA concentration in various pathologies. Despite continuous research on these issues, the molecular mechanisms in the regulation of the intracellular level of CoA under pathological conditions are still not well understood. This review summarizes the current knowledge of (a) CoA subcellular concentrations; (b) the roles of CoA synthesis and degradation processes; and (c) protein modification by reversible CoA binding to proteins (CoAlation). Particular attention is paid to (a) the roles of changes in the level of CoA under pathological conditions, such as in neurodegenerative diseases, cancer, myopathies, and infectious diseases; and (b) the beneficial effect of CoA and pantethine (which like CoA is finally converted to Pan and cysteamine), used at pharmacological doses for the treatment of hyperlipidemia.

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Background/Aim: Fatty acid synthase (FASN) provides palmitate for cell membrane formation in colorectal cancer (CRC) cells, however, palmitate is also available in the blood of CRC patients. The aim of this study was to examine whether orlistat, a FASN inhibitor, is able to attenuate CRC cell growth despite the availability of extracellular palmitate. Materials and Methods: Palmitate concentrations were measured in serum from CRC patients and healthy controls. HT-29 CRC cells were treated with orlistat and palmitate. Results: Treatment of CRC cells with orlistat caused a dose-dependent inhibition of cell proliferation. In turn, delivery of extracellular palmitate at doses lower than those found in the serum of CRC patients reversed inhibition by orlistat concentrations of up to 10 μM. Conclusion: Inhibition of CRC cell proliferation by orlistat is reversed by palmitate which is present at high levels in the serum. Therefore, orlistat may be effective in vivo only at high concentrations.Colorectal cancer (CRC) is one of the leading causes of mortality among cancer patients, and the search for new therapies is still underway. Due to advances in screening techniques and improvements in treatments, the death rate from colorectal cancer has been decreasing in the United States and Europe. However, a trend of increasing incidence of the disease has been observed in recently developed countries (1). This cancer tends to affect men and women equally, but men tend to develop it at a younger age (2). CRC can often be sporadic; however, hereditary forms are also common in this entity (2). Recent evidence shows that CRC is associated with considerable changes in lipid composition and metabolism in cancer cells (3, 4). One of the alterations characteristic of many cancers is enhanced lipogenesis, a process that provides lipids for cell membrane formation in rapidly proliferating cancer cells (5). Some authors have reported overexpression of fatty acid synthase (FASN), the major enzyme which produces palmitic acid, in CRC tissue (6-8). Furthermore, FASN levels in the serum of colorectal cancer patients are significantly higher than that in healthy individuals; thus, this enzyme may be a potential tumor marker (9). FASN knockdown has been associated with the inhibition of CRC cell proliferation (10). Moreover, FASN expression increases with tumor progression in certain tumor types, including colorectal cancer and is associated with increased disease aggressiveness and diminished survival and response to classical chemotherapeutic agents (11)(12)(13). Thus, research on inhibitors of FASN as potential anticancer therapies is underway (5). Orlistat (tetrahydrolipstatin) is a drug used for the treatment of obesity. Orlistat is an inhibitor of pancreatic and gastric lipase, and its action leads to decreased absorption of dietary fat (14). This agent, which is administered by the oral route, is minimally absorbed by the gastrointestinal tract and reduces the lipid supply from outside sources. However, orlistat is also an inhibitor...

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Overexpression of acyl-coenzyme A:cholesterol acyltransferase (ACAT) results in increased cholesteryl ester levels and has been involved in a variety of cancer types. As a consequence, cholesterol metabolism has raised interest as a potential target for cancer treatment. Inhibition of ACAT results in suppression of proliferation in a range of cancer cell types both in vitro and in vivo. The exact mechanism of this phenomenon is being investigated, and the most important findings are presented in this review.

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