A New Metabolic Link

1997/07/01 by Sean W. Jordan, John E. Cronan · 156 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Alcoholism and Thiamine Deficiency #Biochemical Acid Research Studies #Biochemistry #Biology #Chemistry #Coenzyme Q10 studies and effects #Cofactor #DNA ligase #Dihydrolipoyl transacetylase #Enzyme #Lipoic acid #Oxoglutarate dehydrogenase complex #Protein subunit #Pyruvate dehydrogenase complex #Pyruvate dehydrogenase phosphatase

paper · pdf · doi:10.1074/jbc.272.29.17903

published in Journal of Biological Chemistry 272(29), 17903-17906 (Elsevier BV)

openalex publication_date 1997/07/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/04

Abstract

Lipoic acid is an essential enzyme cofactor that requires covalent attachment to its cognate proteins to confer biological activity. The major lipoylated proteins are highly conserved enzymes of central metabolism, the pyruvate and alpha-ketoglutarate dehydrogenase complexes. The classical lipoate ligase uses ATP to activate the lipoate carboxyl group followed by attachment of the cofactor to a specific subunit of each dehydrogenase complex, and it was assumed that all lipoate attachment proceeded by this mechanism. However, our previous work indicated that Escherichia coli could form lipoylated proteins in the absence of detectable ATP-dependent ligase activity raising the possibility of a class of enzyme that attaches lipoate to the dehydrogenase complexes by a different mechanism. We now report that E. coli and mitochondria contain lipoate transferases that use lipoyl-acyl carrier protein as the lipoate donor. This finding demonstrates a direct link between fatty acid synthesis and lipoate attachment and also provides the first direct demonstration of a role for the enigmatic acyl carrier proteins of mitochondria.

Citations

• STUDIES ON A LIPOIC ACID-ACTIVATING SYSTEM

Cited by

• Lipoic acid metabolism and mitochondrial redox regulation
• Lipoic Acid Synthesis and Attachment in Yeast Mitochondria
• The Escherichia coli lipB Gene Encodes Lipoyl (Octanoyl)-Acyl Carrier Protein:Protein Transferase
• Swinging Arms and Swinging Domains in Multifunctional Enzymes: Catalytic Machines for Multistep Reactions
• Current understanding of fatty acid biosynthesis and the acyl carrier protein
• Bacterial lipids: Metabolism and membrane homeostasis
• S-Adenosylmethionine: A Wolf in Sheep's Clothing, or a Rich Man's Adenosylcobalamin?
• THE STRUCTURAL BIOLOGY OF TYPE II FATTY ACID BIOSYNTHESIS
• Cloning, Expression, Characterization, and Interaction of Two Components of a Human Mitochondrial Fatty Acid Synthase
• Function, Attachment and Synthesis of Lipoic Acid in Escherichia coli
• Expression Cloning and Demonstration of Enterococcus faecalis Lipoamidase (Pyruvate Dehydrogenase Inactivase) as a Ser-Ser-Lys Triad Amidohydrolase
• LplA1-dependent utilization of host lipoyl peptides enables Listeria cytosolic growth and virulence. [europepmc]
• Mitochondrial respiratory complex I: structure, function and implication in human diseases. [europepmc]
• A novel amidotransferase required for lipoic acid cofactor assembly in Bacillus subtilis. [europepmc]
• Neuroprotective effects of alpha lipoic Acid on haloperidol-induced oxidative stress in the rat brain. [europepmc]
• Discovery of a metagenome-derived enzyme that produces branched-chain acyl-(acyl-carrier-protein)s from branched-chain α-keto acids. [europepmc]
• Resin-based investigation of acyl carrier protein interaction networks in Escherichia coli. [europepmc]
• Bacterial lipids: metabolism and membrane homeostasis. [europepmc]
• Trapping the dynamic acyl carrier protein in fatty acid biosynthesis. [europepmc]
• Versatility of acyl-acyl carrier protein synthetases. [europepmc]
• Biotin and Lipoic Acid: Synthesis, Attachment, and Regulation. [europepmc]
• Protein lipoylation: an evolutionarily conserved metabolic regulator of health and disease. [europepmc]
• Lipoic acid metabolism and mitochondrial redox regulation. [europepmc]
• Impact of Mitochondrial Fatty Acid Synthesis on Mitochondrial Biogenesis. [europepmc]
• A Single Tool to Monitor Multiple Protein-Protein Interactions of the Escherichia coli Acyl Carrier Protein. [europepmc]
• Alpha-Lipoic Acid Protects Cardiomyocytes against Heat Stroke-Induced Apoptosis and Inflammatory Responses Associated with the Induction of Hsp70 and Activation of Autophagy. [europepmc]
• Alpha-Lipoic Acid Inhibits Spontaneous Diabetes and Autoimmune Recurrence in Non-Obese Diabetic Mice by Enhancing Differentiation of Regulatory T Cells and Showed Potential for Use in Cell Therapies for the Treatment of Type 1 Diabetes. [europepmc]
• A Lipoate-Protein Ligase Is Required for De Novo Lipoyl-Protein Biosynthesis in the Hyperthermophilic Archaeon Thermococcus kodakarensis. [europepmc]
• In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. [europepmc]
• Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism. [europepmc]
• Identification of Au-hydrides as key intermediates in the reduction of Au(iii) prodrugs to active Au(i) species under protic conditions. [europepmc]

Related

• The Escherichia coli lipB Gene Encodes Lipoyl (Octanoyl)-Acyl Carrier Protein:Protein Transferase
• Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes
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• Lipoic acid metabolism in Escherichia coli: the lplA and lipB genes define redundant pathways for ligation of lipoyl groups to apoprotein
• Boosting energy metabolism and biosynthesis in diverse organisms by a common bacterial salvage lipoylation protein