Inhibition of liver acetyl-coenzyme-A carboxylase by 2-tetradecanylglutarate. 1986

H Takeshima, and A Endo, and K Wada, and T Tanabe

In a previous study (A. ENDO, et al., J. Antibiotics 38: 599 approximately 604, 1985), 2-alkyl glutarate and its derivatives isolated from cultures of Gongronella butleri were shown to inhibit animal acetyl-CoA carboxylase. In the present communication, the inhibition of liver acetyl-CoA carboxylase was investigated with several 2-alkyl glutarate and 2-alkyl succinate analogs. Their inhibitory potency increased with the chain length of the alkyl moiety, and 2-tetradecanylglutarate was most potent among the inhibitors tested. Kinetic analysis indicated that inhibition by 2-tetradecanylglutarate was non-competitive with respect to the substrates, ATP, HCO3- and acetyl-CoA, and competitive with respect to the allosteric regulatory citrate, giving a Ki value of 40 microM. Sucrose density gradient centrifugation analysis showed that the citrate-induced polymerization of the enzyme was inhibited by 2-tetradecanylglutarate.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008025 Ligases A class of enzymes that catalyze the formation of a bond between two substrate molecules, coupled with the hydrolysis of a pyrophosphate bond in ATP or a similar energy donor. (Dorland, 28th ed) EC 6. Ligase,Synthetases,Synthetase
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D002499 Centrifugation, Density Gradient Separation of particles according to density by employing a gradient of varying densities. At equilibrium each particle settles in the gradient at a point equal to its density. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Centrifugations, Density Gradient,Density Gradient Centrifugation,Density Gradient Centrifugations,Gradient Centrifugation, Density,Gradient Centrifugations, Density
D002645 Chickens Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA. Gallus gallus,Gallus domesticus,Gallus gallus domesticus,Chicken
D002951 Citrates Derivatives of CITRIC ACID.
D005977 Glutarates Derivatives of glutaric acid (the structural formula (COO-)2C3H6), including its salts and esters. Glutarate
D000103 Acetyl-CoA Carboxylase A carboxylating enzyme that catalyzes the conversion of ATP, acetyl-CoA, and HCO3- to ADP, orthophosphate, and malonyl-CoA. It is a biotinyl-protein that also catalyzes transcarboxylation. The plant enzyme also carboxylates propanoyl-CoA and butanoyl-CoA (From Enzyme Nomenclature, 1992) EC 6.4.1.2. Acetyl Coenzyme A Carboxylase,Acetyl CoA Carboxylase,Carboxylase, Acetyl-CoA
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

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