Acetyl-CoA

Acetyl-CoA
DMacks · Public domain · source
Name	Acetyl-CoA
Caption	Skeletal formula of acetyl coenzyme A
Formula	C23H38N7O17P3S
Molar mass	809.57 g·mol−1

Acetyl-CoA Acetyl-CoA is a central metabolic intermediate that donates two‑carbon acetyl groups in numerous biosynthetic and energy‑yielding pathways. It connects carbohydrate, lipid, and amino acid metabolism and participates in regulation of gene expression and post‑translational modification. Studies across institutions such as National Institutes of Health, Harvard University, Massachusetts Institute of Technology, University of Cambridge, and Max Planck Society have characterized its biochemical roles and implications for disease.

Structure and Properties

The molecule comprises an acetyl moiety thioesterified to coenzyme A, whose pantetheine, adenosine 3',5'‑diphosphate, and 3'‑phosphoadenosine regions derive from components studied by researchers at Pfizer, Roche, Novartis, AstraZeneca, and Sanofi. Chemical features include a reactive thioester bond, polar nucleotide segments, and a variable conformation influenced by interactions observed in complexes solved by groups at European Molecular Biology Laboratory, Stanford University, University of Oxford, California Institute of Technology, and Yale University. Physical properties such as solubility, stability, and reactivity have been characterized in biochemical manuals produced by American Chemical Society, Royal Society of Chemistry, Elsevier, and Wiley. Crystallographic and NMR data contributed by teams at Max Planck Institute for Biophysical Chemistry and Scripps Research have informed models used by UniProt, Protein Data Bank, KEGG, BRENDA, and Reactome.

Biosynthesis and Metabolic Sources

Acetyl groups are transferred to coenzyme A by enzymes investigated by laboratories at Johns Hopkins University, University of California, San Francisco, University of Tokyo, Seoul National University, and University of Melbourne. Pyruvate dehydrogenase complexes characterized in work from Nobel Prize‑associated studies and groups at Columbia University and Princeton University convert pyruvate to acetyl groups, while fatty acid β‑oxidation pathways elucidated by researchers at Imperial College London and Washington University in St. Louis supply acetyl units. Amino acid catabolism described in reports from University of Chicago, University of Toronto, Karolinska Institute, Institut Pasteur, and Weizmann Institute also generates acetyl groups. Bacterial enzymes such as pyruvate:ferredoxin oxidoreductase studied at ETH Zurich and University of Groningen provide alternative routes, and acetate activation via acetyl‑CoA synthetase investigated at Chinese Academy of Sciences and Australian National University contributes a metabolic source.

Roles in Metabolism and Cellular Functions

Acetyl‑CoA donates acetyl groups to the tricarboxylic acid cycle first delineated by researchers at University of Edinburgh, University of California, Berkeley, University of Michigan, Vanderbilt University, and Brown University. It serves as substrate for fatty acid synthesis elucidated in work from Cornell University, University of Illinois Urbana‑Champaign, Michigan State University, University of Wisconsin‑Madison, and Duke University, and for cholesterol biosynthesis whose pathway mapping involved scientists at World Health Organization initiatives and pharmaceutical collaborations. Acetylation of proteins, including histones examined by teams at Cold Spring Harbor Laboratory, Rockefeller University, National Cancer Institute, Dana‑Farber Cancer Institute, and Broad Institute, links acetyl‑CoA availability to regulation of transcription factors studied in contexts such as United Nations‑sponsored health programs. Other roles include synthesis of ketone bodies described by researchers at Mayo Clinic, Cleveland Clinic, Karolinska University Hospital, and Johns Hopkins Hospital, and participation in biosynthesis of neurotransmitters investigated at National Institute of Mental Health and Mount Sinai Health System.

Regulation and Compartmentalization

Subcellular localization and transport mechanisms connecting mitochondria, cytosol, and nucleus have been analyzed by groups at Columbia University Irving Medical Center, University of California, San Diego, New York University, University of Pennsylvania, and Pennsylvania State University. Regulation of acetyl‑CoA levels by enzymes and cofactors studied at Riken, National Institute for Medical Research, Institut Clinique de la Coulée Verte, Karolinska Institute, and Institut Curie involves signaling pathways described in papers from European Commission‑funded consortia and consortia including Horizon 2020. Compartmental pools influence chromatin acetylation as documented in collaborations between Salk Institute, Buck Institute, Fred Hutchinson Cancer Center, John Innes Centre, and INRAE.

Clinical Significance and Disease Associations

Altered acetyl‑CoA metabolism is implicated in metabolic disorders researched at American Diabetes Association, World Health Organization, Centers for Disease Control and Prevention, National Health Service (England), and specialty centers like Joslin Diabetes Center. Cancer metabolism involving acetyl‑CoA flux has been studied at Memorial Sloan Kettering Cancer Center, Dana‑Farber Cancer Institute, MD Anderson Cancer Center, University College London Hospitals, and Royal Marsden Hospital. Neurodegenerative diseases linked to acetylation dynamics have been explored at Alzheimer's Association, Michael J. Fox Foundation, Parkinson's Foundation, Massachusetts General Hospital, and Karolinska University Hospital. Inborn errors of metabolism affecting enzymes that generate or utilize acetyl‑CoA have been reported by networks including European Rare Disease Consortium, Orphanet, Genomics England, 23andMe, and Illumina.

Experimental Methods and Measurement

Quantitation and tracing of acetyl‑CoA employ mass spectrometry platforms and stable isotope tracers developed by companies and labs at Thermo Fisher Scientific, Agilent Technologies, Bruker, Oxford Nanopore Technologies, and academic groups at University of California, Irvine, University of Colorado Denver, University of Sydney, University of Hong Kong, and McGill University. Enzymology assays referenced in protocols from Cold Spring Harbor Protocols, Nature Protocols, Methods in Enzymology, Biochemical Journal, and Journal of Biological Chemistry provide activity measurements. Chromatin immunoprecipitation and acetylation mapping techniques advanced at EMBL‑EBI, Wellcome Trust Sanger Institute, Genome Research Limited, European Bioinformatics Institute, and International HapMap Project connect acetyl‑CoA availability to epigenomic states.

Evolutionary and Comparative Aspects

Acetyl‑CoA‑related enzymes show conservation and divergence across domains of life identified by comparative genomics groups at National Center for Biotechnology Information, European Molecular Biology Laboratory, Joint Genome Institute, Broad Institute, and Wellcome Sanger Institute. Studies of ancient metabolic pathways and horizontal gene transfer involving acetyl‑CoA enzymes have involved paleobiology and astrobiology teams at Smithsonian Institution, NASA, California Academy of Sciences, Natural History Museum, London, and Field Museum of Natural History. Comparative physiology investigations in organisms ranging from Escherichia coli studies at Cold Spring Harbor Laboratory to plant work at Rothamsted Research and animal models at Stanford University School of Medicine illuminate adaptive roles of acetyl‑CoA metabolism.

Category:Metabolism