Ultrasound guided sclerotherapy combined with sapheno-femoral ligation was less expensive, involved a shorter treatment time and resulted in more rapid recovery compared to sapheno-femoral ligation, saphenous stripping and phlebectomies.

Delaminated carbon nitride nanosheets were prepared by high-temperature H2 treatment of bulk carbon nitride with defects being introduced during this treatment. Although the defects can act as traps for charge carriers, reducing photoluminescence lifetime, they also form highly active photocatalytic sites for hydrogen evolution. The nanostructured materials exhibit substantially enhanced photocatalytic activity due to a synergistic effect between delamination, the presence of defects, and associated band gap changes.

Meeting the complex physiological demands of mammalian life requires strict control of the metabolism of long-chain fatty acyl-CoAs because of the multiplicity of their cellular functions. Acyl-CoAs are substrates for energy production; stored within lipid droplets as triacylglycerol, cholesterol esters, and retinol esters; esterified to form membrane phospholipids; or used to activate transcriptional and signaling pathways. Indirect evidence suggests that acyl-CoAs do not wander freely within cells, but instead, are channeled into specific pathways. In this review, we will discuss the evidence for acyl-CoA compartmentalization, highlight the key modes of acyl-CoA regulation, and diagram potential mechanisms for controlling acylCoA partitioning.Two prevailing views of metabolic pathways within the cytosol are a) as sequential steps within a largely empty space with substrates and products traveling from one enzyme to the next, and b), as embedded within a dense network of proteins and metabolites, all jockeying for position. In contrast to these two views, it is likely that synthetic and degradative pathways are composed of enzymes and their regulators in highly organized multi-enzyme assemblies designed to enhance efficiency and regulate steady-state flux (1). Proteins within these assemblies might interact via their transmembrane and extra-membrane domains or be tethered to scaffolds, in a manner that is regulated by allosteric effectors and post-translational modifications (2, 3). Such interactions may be transient, as occurs with the enzymes that comprise purinosomes (4), or they may be semi-permanent as occurs within glycogen granules that contain enzymes that synthesize and degrade glycogen, and their regulatory kinases and phosphatases (5, 6). Assemblies of proteins are advantageous because even without a physical tunnel, they can increase reaction rates by enhancing local substrate concentrations, restricting intermediates from entering competing reactions, and stabilizing chemically unstable intermediates.Because the dysregulation of metabolic homeostasis has been implicated in a multitude of human diseases, acyl-CoA metabolism represents a critical node for understanding whole-body pathophysiology. Apart from eicosanoid synthesis, the first step in the metabolism of long-chain fatty acids (FAs) 2 is their thioesterification. The resulting acyl-CoA is then metabolized by one of six major enzyme families: elongases and desaturases (7), dehydrogenases (8, 9), acyl-CoA thioesterases (10, 11), carnitine palmitoyltransferases (CPT) (12), and lipid and protein acyltransferases (13) (Fig. 1). These competing pathways, often present within a single subcellular compartment and coupled with the highly specialized metabolism of individual cells and tissues, suggest a level of organization extending beyond enzymatic function. In this review, we will use a physiological lens to focus on longchain mammalian fatty acyl-CoAs and the evidence for compartmentalized acyl-CoA metabolism.

Fatty acid channeling into oxidation or storage modes depends on physiological conditions and hormonal signaling. However, the directionality of this channeling may also depend on the association of each of the five acyl-CoA synthetase isoforms with specific protein partners. Long-chain acyl-CoA synthetases (ACSLs) catalyze the conversion of long-chain fatty acids to fatty acyl-CoAs, which are then either oxidized or used in esterification reactions. In highly oxidative tissues, ACSL1 is located on the outer mitochondrial membrane (OMM) and directs fatty acids into mitochondria for β-oxidation. In the liver, however, about 50% of ACSL1 is located on the endoplasmic reticulum (ER) where its metabolic function is unclear. Because hepatic fatty acid partitioning is likely to require the interaction of ACSL1 with other specific proteins, we used an unbiased protein interaction technique, BioID, to discover ACSL1-binding partners in hepatocytes. We targeted ACSL1 either to the ER or to the OMM of Hepa 1-6 cells as a fusion protein with the biotin ligase, BirA*. Proteomic analysis identified 98 proteins that specifically interacted with ACSL1 at the ER, 55 at the OMM, and 43 common to both subcellular locations. We found subsets of peroxisomal and lipid droplet proteins, tethering proteins, and vesicle proteins, uncovering a dynamic role for ACSL1 in organelle and lipid droplet interactions. Proteins involved in lipid metabolism were also identified, including acyl-CoA-binding proteins and ceramide synthase isoforms 2 and 5. Our results provide fundamental and detailed insights into protein interaction networks that control fatty acid metabolism.