Biomaterial Database

A top-down control analysis in isolated rat liver mitochondria: can the 3-hydroxy-3-methylglutaryl-CoA pathway be rate-controlling for ketogenesis? 1993

P A Quant, and D Robin, and P Robin, and J Girard, and M D Brand

Centre de Recherche sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique, Meudon-Bellevue, France.

We incubated isolated liver mitochondria with palmitoyl-CoA, 2,4-dinitrophenol and malonate. Under these conditions all the flux of carbon from palmitoyl-CoA was directed towards acetoacetate synthesis. We measured the rate of acetyl-CoA formation from palmitoyl-CoA (by measuring the rate of oxygen consumption) and the rate of acetoacetate production from acetyl-CoA at three different acetyl-CoA/CoA ratios. Using the top-down approach of metabolic control analysis we calculated the control over ketogenesis exerted by (a) the conversion of extramitochondrial palmitoyl-CoA to intramitochondrial acetyl-CoA and by (b) the conversion of acetyl-CoA to acetoacetate (the 'HMG-CoA pathway'). The overall flux control coefficients of the groups of enzymes involved in (a) and (b) over ketogenesis were 0.28 and 0.72, respectively. Our results show that it is possible for significant control to be exerted over ketogenesis by the enzymes of the HMG-CoA pathway.

UI	MeSH Term	Description	Entries
D007657	Ketone Bodies	The metabolic substances ACETONE; 3-HYDROXYBUTYRIC ACID; and acetoacetic acid (ACETOACETATES). They are produced in the liver and kidney during FATTY ACIDS oxidation and used as a source of energy by the heart, muscle and brain.	Acetone Bodies,Bodies, Acetone,Bodies, Ketone
D007659	Ketones	Organic compounds containing a carbonyl group	Ketone
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008433	Mathematics	The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Mathematic
D008930	Mitochondria, Liver	Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4)	Liver Mitochondria,Liver Mitochondrion,Mitochondrion, Liver
D008956	Models, Chemical	Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.	Chemical Models,Chemical Model,Model, Chemical
D010171	Palmitoyl Coenzyme A	A fatty acid coenzyme derivative which plays a key role in fatty acid oxidation and biosynthesis.	Palmitoyl CoA,Hexadecanoyl CoA,Palmityl CoA,CoA, Hexadecanoyl,CoA, Palmitoyl,CoA, Palmityl,Coenzyme A, Palmitoyl
D000090	Acetoacetates	Salts and derivatives of acetoacetic acid.
D000214	Acyl Coenzyme A	S-Acyl coenzyme A. Fatty acid coenzyme A derivatives that are involved in the biosynthesis and oxidation of fatty acids as well as in ceramide formation.	Acyl CoA,Fatty Acyl CoA,Long-Chain Acyl CoA,Acyl CoA, Fatty,Acyl CoA, Long-Chain,CoA, Acyl,CoA, Fatty Acyl,CoA, Long-Chain Acyl,Coenzyme A, Acyl,Long Chain Acyl 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