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Synaptic plasma membrane Na(+), K (+)-ATPase activity is significantly reduced by the alpha-keto acids accumulating in maple syrup urine disease in rat cerebral cortex.
Metab Brain Dis. 2007 Mar; 22(1):77-88.MB

Abstract

The objective of the present study was to investigate the in vitro effects of the branched-chain alpha-keto acids accumulating in maple syrup urine disease, namely L-2-ketoisocaproic acid, L-2-keto-3-methylvaleric acid and L-2-ketoisovaleric acid on Na(+), K(+)-ATPase activity in synaptic plasma membranes from cerebral cortex of 35-day-old rats. All keto acids significantly inhibited Na(+), K(+)-ATPase activity at concentrations similar (1 mM) or even lower (0.5 mM) than those found in blood and cerebrospinal fluid of maple syrup urine disease patients. We also tested the effects of alanine on this enzyme activity. Alanine per se did not alter Na(+), K(+)-ATPase activity, but totally prevented the branched-chain alpha-keto acids-induced Na(+), K(+)-ATPase inhibition, indicating that alanine and the keto acids may possibly bind to the same site on the enzyme. We also observed that the branched-chain amino acids leucine, isoleucine and valine also inhibited Na(+) K(+)-ATPase activity to a similar degree as that of the branched-chain alpha-keto acids and that alanine was able to fully prevent these effects. Considering that Na(+), K(+)-ATPase is a critical enzyme for normal brain development and functioning, it is presumed that these findings may be involved in the pathophysiology of the neurological dysfunction of maple syrup urine disease.

Authors+Show Affiliations

Departamento de Bioquímica, Institute de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos, 2600-Anexo, CEP: 90035-003, Porto Alegre, RS, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17295076

Citation

Wajner, André, et al. "Synaptic Plasma Membrane Na(+), K (+)-ATPase Activity Is Significantly Reduced By the Alpha-keto Acids Accumulating in Maple Syrup Urine Disease in Rat Cerebral Cortex." Metabolic Brain Disease, vol. 22, no. 1, 2007, pp. 77-88.
Wajner A, Bürger C, Dutra-Filho CS, et al. Synaptic plasma membrane Na(+), K (+)-ATPase activity is significantly reduced by the alpha-keto acids accumulating in maple syrup urine disease in rat cerebral cortex. Metab Brain Dis. 2007;22(1):77-88.
Wajner, A., Bürger, C., Dutra-Filho, C. S., Wajner, M., de Souza Wyse, A. T., & Wannmacher, C. M. (2007). Synaptic plasma membrane Na(+), K (+)-ATPase activity is significantly reduced by the alpha-keto acids accumulating in maple syrup urine disease in rat cerebral cortex. Metabolic Brain Disease, 22(1), 77-88.
Wajner A, et al. Synaptic Plasma Membrane Na(+), K (+)-ATPase Activity Is Significantly Reduced By the Alpha-keto Acids Accumulating in Maple Syrup Urine Disease in Rat Cerebral Cortex. Metab Brain Dis. 2007;22(1):77-88. PubMed PMID: 17295076.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synaptic plasma membrane Na(+), K (+)-ATPase activity is significantly reduced by the alpha-keto acids accumulating in maple syrup urine disease in rat cerebral cortex. AU - Wajner,André, AU - Bürger,Cristiane, AU - Dutra-Filho,Carlos Severo, AU - Wajner,Moacir, AU - de Souza Wyse,Angela Terezinha, AU - Wannmacher,Clóvis Milton Duval, PY - 2007/2/14/pubmed PY - 2007/7/19/medline PY - 2007/2/14/entrez SP - 77 EP - 88 JF - Metabolic brain disease JO - Metab Brain Dis VL - 22 IS - 1 N2 - The objective of the present study was to investigate the in vitro effects of the branched-chain alpha-keto acids accumulating in maple syrup urine disease, namely L-2-ketoisocaproic acid, L-2-keto-3-methylvaleric acid and L-2-ketoisovaleric acid on Na(+), K(+)-ATPase activity in synaptic plasma membranes from cerebral cortex of 35-day-old rats. All keto acids significantly inhibited Na(+), K(+)-ATPase activity at concentrations similar (1 mM) or even lower (0.5 mM) than those found in blood and cerebrospinal fluid of maple syrup urine disease patients. We also tested the effects of alanine on this enzyme activity. Alanine per se did not alter Na(+), K(+)-ATPase activity, but totally prevented the branched-chain alpha-keto acids-induced Na(+), K(+)-ATPase inhibition, indicating that alanine and the keto acids may possibly bind to the same site on the enzyme. We also observed that the branched-chain amino acids leucine, isoleucine and valine also inhibited Na(+) K(+)-ATPase activity to a similar degree as that of the branched-chain alpha-keto acids and that alanine was able to fully prevent these effects. Considering that Na(+), K(+)-ATPase is a critical enzyme for normal brain development and functioning, it is presumed that these findings may be involved in the pathophysiology of the neurological dysfunction of maple syrup urine disease. SN - 0885-7490 UR - https://www.unboundmedicine.com/medline/citation/17295076/Synaptic_plasma_membrane_Na_+__K__+__ATPase_activity_is_significantly_reduced_by_the_alpha_keto_acids_accumulating_in_maple_syrup_urine_disease_in_rat_cerebral_cortex_ L2 - https://doi.org/10.1007/s11011-007-9046-5 DB - PRIME DP - Unbound Medicine ER -