The Physiological and Pathological Role of Acyl-CoA Oxidation.

Fatty acid metabolism, including ß-oxidation (ßOX), plays an important role in human physiology and pathology. ßOX is an essential process in the energy metabolism of most human cells. Moreover, ßOX is also the source of acetyl-CoA, the substrate for (a) ketone bodies synthesis, (b) cholesterol synthesis, (c) phase II detoxication, (d) protein acetylation, and (d) the synthesis of many other compounds, including N-acetylglutamate-an important regulator of urea synthesis. This review describes the current knowledge on the importance of the mitochondrial and peroxisomal ßOX in various organs, including the liver, heart, kidney, lung, gastrointestinal tract, peripheral white blood cells, and other cells. In addition, the diseases associated with a disturbance of fatty acid oxidation (FAO) in the liver, heart, kidney, lung, alimentary tract, and other organs or cells are presented. Special attention was paid to abnormalities of FAO in cancer cells and the diseases caused by mutations in gene-encoding enzymes involved in FAO. Finally, issues related to α- and ω- fatty acid oxidation are discussed.

The Role of Acyl-CoA ß-Oxidation in Brain Metabolism and Neurodegenerative Diseases.

This review highlights the complex role of fatty acid ß-oxidation in brain metabolism. It demonstrates the fundamental importance of fatty acid degradation as a fuel in energy balance and as an essential component in lipid homeostasis, brain aging, and neurodegenerative disorders.

High levels of reactive oxygen species in pancreatic necrotic fluid of patients with walled-off pancreatic necrosis.

INTRODUCTION: Walled-off pancreatic necrosis (WOPN) is a life-threatening, late complication of acute pancreatitis, in which a fluid collection containing necrotic material is formed. Infection of the fluid collection significantly increases the mortality of patients with WOPN. AIM: To examine the levels of oxidative stress markers in the pancreatic necrotic fluid (PNF) and serum of patients with sterile and infected WOPN. MATERIAL AND METHODS: Thirty-three adult patients with sterile WOPN and 14 with infected WOPN, as well as 31 patients with mild AP, were included in this study. Concentrations of oxidative stress markers (8-isoprostane, protein carbonyl groups, and 8-hydroxyguanine) were measured in the PNF and serum of patients with sterile and infected WOPN. RESULTS: High concentrations of all measured oxidative stress markers in PNF, but not in serum, were detected in patients with WOPN. Additionally, oxidative stress markers in PNF were significantly increased in patients with infected as compared to sterile WOPN. The serum high sensitive C-reactive protein (hsCRP) concentrations showed the highest correlation with PNF oxidative stress marker levels. Receiver operating characteristics (ROC) curve analysis confirmed that serum hsCRP could be a good predictor of WOPN infection. CONCLUSIONS: Oxidative stress is associated with WOPN development; infection of PNF worsens the course of WOPN, possibly via increased production of reactive oxygen species; and serum hsCRP concentrations seem to be a good, noninvasive indicator of PNF infection.

The Pathophysiological Role of CoA.

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.