Acyl-CoA

About: Acyl-CoA is a research topic. Over the lifetime, 527 publications have been published within this topic receiving 25134 citations. The topic is also known as: Acyl Coenzyme A.

Minireview: malonyl CoA, AMP-activated protein kinase, and adiposity

Abstract: An increasing body of evidence has linked AMP-activated protein kinase (AMPK) and malonyl coenzyme A (CoA) to the regulation of energy balance. Thus, factors that activate AMPK and decrease the concentration of malonyl CoA in peripheral tissues, such as exercise, decrease triglyceride accumulation in the adipocyte and other cells. The data reviewed here suggest that this is related to the fact that these factors concurrently increase fatty acid oxidation, decrease the esterification of fatty acids to form glycerolipids, and, by mechanisms still unknown, increase energy expenditure. Malonyl CoA contributes to these events because it is an allosteric inhibitor of carnitine palmitoyltransferase, the enzyme that controls the transfer of long-chain fatty acyl CoA from the cytosol to the mitochondria, where they are oxidized. AMPK activation in turn increases fatty acid oxidation (by effects on enzymes that govern malonyl CoA synthesis and possibly its degradation) and inhibits triglyceride synthesis. It also increases the expression of uncoupling proteins and the transcriptional regulator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha), which could possibly increase energy expenditure. Recent studies suggest that the ability of leptin, adiponectin, 5'-aminoimidazole 4-carboxamide riboside (AICAR), adrenergic agonists, and metformin to diminish adiposity may be mediated, at least in part, by AMPK activation in peripheral tissues. In addition, preliminary studies suggest that malonyl CoA and AMPK take part in fuel-sensing and signaling mechanisms in the hypothalamus that could regulate food intake and energy expenditure.

Disorders of mitochondrial fatty acyl-CoA β-oxidation

Abstract: In recent years tremendous progress has been made with respect to the enzymology of the mitochondrial fatty acid β-oxidation machinery and defects therein. Firstly, a number of new mitochondrial β-oxidation enzymes have been identified, including very-long-chain acyl-CoA dehydrogenase (VLCAD) and mitochondrial trifunctional protein (MTP). Secondly, the introduction of tandem MS for the analysis of plasma acylcarnitines has greatly facilitated the identification of patients with a defect in fatty acid oxidation (FAO). These two developments explain why the number of defined FAO disorders has increased dramatically, making FAO disorders the most rapidly growing group of inborn errors of metabolism. In this review we describe the current state of knowledge of the enzymes involved in the mitochondrial oxidation of straight-chain, branched-chain and (poly)unsaturated fatty acyl-CoAs as well as disorders of fatty acid oxidation. The laboratory diagnosis of these disorders is described, with particular emphasis on the methods used to identify the underlying enzyme defect and the molecular mutations. In addition, a simple flowchart is presented as a guide to the identification of mitochondrial FAO-disorders. Finally, treatment strategies are discussed briefly.