Propionic and methylmalonic acids inhibit the in vitro phosphorylation of a 85 kDa cytoskeletal protein from cerebral cortex of rats. 1998

A de Mattos-Dutra, and M Sampaio de Freitas, and M Wajner, and R Pessoa-Pureur
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.

In this study we examine the action of methylmalonic (MMA) and propionic (PA) acids, metabolites which accumulate in methylmalonic and propionic acidemias respectively, on the endogenous phosphorylating system associated with the cytoskeletal fraction of cerebral cortex of young rats. Chronic treatment with PA and treatment of tissue slices with MMA or PA are effective in decreasing the in vitro phosphorylation into a 85 kDa cytoskeletal associated protein. We tested the effect of the acids on the endogenous kinase activities by using specific kinase activators and inhibitors. Results demonstrated that the acids interfere with the endogenous cAMP-dependent and Ca2+/calmodulin-dependent kinase activities. Furthermore, in vitro dephosphorylation of the 85 kDa protein was totally inhibited in brain slices treated with the acids. Considering the importance of protein phosphorylation to cellular function, we speculate that alteration in the phosphorylating level of cytoskeletal associated phosphoproteins induced by MMA and PA treatments may somehow be involved in steps leading to brain damage.

UI MeSH Term Description Entries
D008764 Methylmalonic Acid A malonic acid derivative which is a vital intermediate in the metabolism of fat and protein. Abnormalities in methylmalonic acid metabolism lead to methylmalonic aciduria. This metabolic disease is attributed to a block in the enzymatic conversion of methylmalonyl CoA to succinyl CoA. Acid, Methylmalonic
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011422 Propionates Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure. Propanoate,Propanoic Acid,Propionate,Propanoates,Propanoic Acid Derivatives,Propanoic Acids,Propionic Acid Derivatives,Propionic Acids,Acid, Propanoic,Acids, Propanoic,Acids, Propionic,Derivatives, Propanoic Acid,Derivatives, Propionic Acid
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D003598 Cytoskeletal Proteins Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. Proteins, Cytoskeletal
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
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D054732 Calcium-Calmodulin-Dependent Protein Kinase Type 2 A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Ca(2+)-Calmodulin Dependent Protein Kinase Type II,CaCMKII,CaM KII,CaM KIIalpha,CaM KIIbeta,CaM KIIdelta,CaM Kinase II,CaM Kinase II alpha,CaM Kinase II beta,CaM Kinase II delta,CaM Kinase II gamma,CaM PK II,CaM-Kinase II,CaM-Kinase IIalpha,CaMKII,CaMKIIgamma,Calcium-Calmodulin Dependent Protein Kinase II beta,Calcium-Calmodulin Dependent Protein Kinase II delta,Calcium-Calmodulin Dependent Protein Kinase II gamma,Calcium-Calmodulin Protein Kinase II,Calcium-Calmodulin-Dependent PK Type II,Calcium-Calmodulin-Dependent Protein Kinase Type 2 alpha Subunit,Calcium-Calmodulin-Dependent Protein Kinase Type 2 beta Subunit,Calcium-Calmodulin-Dependent Protein Kinase Type 2 delta Subunit,Calcium-Calmodulin-Dependent Protein Kinase Type 2 gamma Subunit,Calcium-Dependent CaM Kinase II,Calmodulin Kinase IIalpha,Calmodulin-Dependent Protein Kinase II,CaM Kinase IIalpha,Calcium Calmodulin Dependent PK Type II,Calcium Calmodulin Dependent Protein Kinase II beta,Calcium Calmodulin Dependent Protein Kinase II delta,Calcium Calmodulin Dependent Protein Kinase II gamma,Calcium Calmodulin Dependent Protein Kinase Type 2,Calcium Calmodulin Dependent Protein Kinase Type 2 alpha Subunit,Calcium Calmodulin Dependent Protein Kinase Type 2 beta Subunit,Calcium Calmodulin Dependent Protein Kinase Type 2 delta Subunit,Calcium Calmodulin Dependent Protein Kinase Type 2 gamma Subunit,Calcium Calmodulin Protein Kinase II,Calcium Dependent CaM Kinase II,Calmodulin Dependent Protein Kinase II
D017868 Cyclic AMP-Dependent Protein Kinases A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition. Adenosine Cyclic Monophosphate-Dependent Protein Kinases,Protein Kinase A,cAMP Protein Kinase,cAMP-Dependent Protein Kinases,Cyclic AMP-Dependent Protein Kinase,cAMP-Dependent Protein Kinase,Adenosine Cyclic Monophosphate Dependent Protein Kinases,Cyclic AMP Dependent Protein Kinase,Cyclic AMP Dependent Protein Kinases,Protein Kinase, cAMP,Protein Kinase, cAMP-Dependent,Protein Kinases, cAMP-Dependent,cAMP Dependent Protein Kinase,cAMP Dependent Protein Kinases

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