Lipids of Dermatophytes
Rajendra Prasad, Mahmoud A. Ghannoum in Lipids of Pathogenic Fungi, 2017
From the information available on dermatophytes, it seems that extensive work has been done on lipid composition and its biosynthesis using different precursors but some of the enzymes of biosynthetic and catabolic pathways need further attention. From the enzymes identified in dermatophytes, it is clear that the main pathways of lipid metabolism are common with yeast and other fungi. The lipid catabolizing enzymes, lipases and phospholipases, were suggested to be involved in pathogenesis of this fungus, around three decades back, but to date not much work has been done in this direction and the exact role is still not known. Preliminary studies on the role of second messengers cAMP, Ca2+ and calmodulin122-138 in lipid synthesis have recently been carried out; however, more work is needed in this area to elucidate the exact mechanism of action. Another aspect which demands further research is regulation of phospholipid synthesis and its correlation with the synthesis of other macromolecules.122-138 Further, the role of acyl carrier protein(s) in fatty acid and phospholipid synthesis should also be examined.
Biology of microbes
Philip A. Geis in Cosmetic Microbiology, 2006
Synthesis of lipids. Fatty acid synthesis is catalyzed with fatty acid synthetase using acetyl-CoA and malonyl-CoA as the substrates and NADPH as the reductant. Malonyl-CoA comes from an ATP-driven carboxylation (addition of CO2) of acetyl-CoA that comes from glycolysis. Both acetate and malonate are transferred from coenzyme A to the sulfhydryl group of the acyl carrier protein (ACP) that carries the growing fatty acid chain during synthesis. The synthetase adds two carbons at a time to the carboxyl end of the growing fatty acid chain in a two-stage process. First, malonyl-ACP reacts with a fatty acyl-ACP and yields CO2 and a fatty acyl-ACP that is now two carbons longer. Glycerol can be esterified to fatty acids to result in phosphatidic acid and then to phospholipids that are essential to membrane function.
Micronutrients
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
Vitamin B5 or pantothenic acid is an essential micronutrient required for the biosynthesis of coenzyme A. Coenzyme A (CoA) is a key cofactor in the citric acid cycle or the Krebs cycle, as well as in the metabolism of fatty acid. Pantothenic acid is also present at the active site of acyl carrier protein (ACP) (3, 9, 33, 43). About 85% of dietary pantothenic acid is as CoA and phosphopantetheine. All tissues are capable of forming CoA from pantothenic acid (33). Pantothenic acid is required for the synthesis of several essential molecules including sphingolipids, leucine, arginine, methionine, cholesterol, steroid hormones, vitamin A, vitamin D, and heme A. CoA provides the essential acetyl group to the neurotransmitter acetylcholine, to serotonin in its conversion to melatonin, and to the acetylated sugars present in glycoproteins and glycolipids (N-acetylglucosamine, N-acetylgalactosamine, and N-acetylneuramic acid) (33). Pantothenic acid lotion may promote healthy hair. Vitamin B5 has been suggested to aid in wound healing and to prevent acne. Vitamin B5 supplement could also reduce pain in patients with rheumatoid arthritis (33, 43). A deficiency of vitamin B5 is rare, but some benign symptoms may appear such as fatigue, insomnia, acne, dermatitis, irritability, epigastric distress with anorexia and constipation, numbness and tingling of the hands and feet, and stomach pains (3). No toxicity as a result of pantothenic acid excess has been identified at the dosages used (9, 33, 43).
Clostridioides difficile: innovations in target discovery and potential for therapeutic success
Published in Expert Opinion on Therapeutic Targets, 2021
Tanya M Monaghan, Anna M Seekatz, Benjamin H Mullish, Claudia C. E. R Moore-Gillon, Lisa F. Dawson, Ammar Ahmed, Dina Kao, Weng C Chan
Fatty acids play a crucial role in the maintenance of the integrity of bacterial cell membranes, and their biosynthesis, as part of the non-mammalian type II fatty acid synthase (FASII) pathway, is mediated by a multitude of interlinked acyl carrier proteins (ACPs) in the cytoplasm [61,62]. Substrates of this pathway are bound to ACPs such as FabD, FabF and FabG, and undergo a series of reactions to extend their acyl chains; each elongation cycle is culminated by reduction, which is catalyzed by an enoyl-acyl carrier protein reductase. These enzymes thus serve as suitable antimicrobial targets, an example of which is isoniazid, an antibiotic used in treating Mycobacterium tuberculosis, and one which functions by inhibiting the reductase FabI [63]. Since bacterial species utilize specifically distinct enoyl-ACP reductases, its inhibition additionally provides a selective antimicrobial target. For instance, triclosan, another known FabI inhibitor, does not inhibit reductases such as FabK and FabV [64,65]. Although not as extensively studied as FabI, FabK has previously been reported as the sole reductase present in Streptococcus pneumoniae [66], and this has led to the identification of FabK inhibitors [67], including compounds derived from phenylimidazole [68].
Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy
Published in Expert Opinion on Investigational Drugs, 2018
Alejandro Schcolnik-Cabrera, Alma Chávez-Blanco, Guadalupe Domínguez-Gómez, Lucia Taja-Chayeb, Rocio Morales-Barcenas, Catalina Trejo-Becerril, Enrique Perez-Cardenas, Aurora Gonzalez-Fierro, Alfonso Dueñas-González
In 1989, the antigen OA-519 was identified as a prognostic molecule in breast cancer [27]. Later on, this antigen was identified as a functional FASN protein through sequencing and enzymatic studies [28]. Under normal conditions, FASN converts excess carbohydrate into FAs that are then esterified to storage triacylglycerols [29,30]. Thus, diet-derived and de novo synthesis are the two main sources of FA both in normal and pathological conditions. The synthesis is catalyzed by the 250–270 kD multifunctional, homodimeric FASN using acetyl-CoA as a primer, malonyl-CoA as a two-carbon donor, and NADPH as a reducing equivalent. FASN has a unique structure and mode of action. The enzyme contains seven separate enzymatic pockets and an acyl carrier protein. These enzyme domains operate together to condense acetyl-CoA and malonyl-CoA, ultimately generating the 16 carbon polyunsaturated fatty acid palmitate, which is the end product of this enzyme [31,32].
A double-blind, 377-subject randomized study identifies Ruminococcus, Coprococcus, Christensenella, and Collinsella as long-term potential key players in the modulation of the gut microbiome of lactose intolerant individuals by galacto-oligosaccharides
Published in Gut Microbes, 2021
M. A. Azcarate-Peril, J. Roach, A. Marsh, William D. Chey, William J. Sandborn, Andrew J. Ritter, Dennis A. Savaiano, T. R. Klaenhammer
Genes responsible for initiation of fatty acid biosynthesis were overrepresented in the GOS groups (Figure 5c). These included FabH (3-ketoacyl- acyl carrier protein [ACP] synthase III), which catalyzes the condensation of acetyl-CoA with malonyl-ACP to yield acetoacetyl-ACP and has transacylase activity, transferring the acetate moiety from actyl-CoA to acetyl-ACP. Acetyl-ACP is then condensed with malonyl-ACP by FabB (synthase I) or by FabF (synthase II), also overrepresented in the GOS groups. The pathway for initiation of fatty acid biosynthesis, which involves decarboxylation of malonyl-ACP by FabH, FabB or FabF to form acetyl-ACP followed by subsequent condensation with malonyl-ACP, was also overrepresented in the GOS groups. All the enzymatic steps involved in elongation of fatty acids from Butyryl-ACP to Stearoyl-CoA were overrepresented in the GOS groups. Also of relevance is that the enzymatic step to convert Acetyl-CoA to Malonyl-CoA is present in the metabolism of propionic acid, a carboxylic short chain fatty acid (SCFA). Likewise, this step is important in the biosynthesis of fatty acids. Furthermore, the type I Fatty acid synthase gene (Fas), essential for subsequent steps in the biosynthetic pathway, was overrepresented in the GOS groups.
Related Knowledge Centers
- Fatty Acid
- Fatty Acid Synthase
- Polyketide
- Phosphopantetheine
- Nuclear Magnetic Resonance Spectroscopy of Proteins
- NONribosomal Peptide
- Holo-(Acyl-Carrier-Protein) Synthase