Linked Life Data

11673873

Source:http://linkedlifedata.com/resource/pubmed/id/11673873

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-10-24
pubmed:abstractText
The most common mutation in the alpha subunit of the pyruvate dehydrogenase (E1) component of the human pyruvate dehydrogenase complex (PDC) is arginine-234 to glycine and glutamine in 12 and 3 patients, respectively. Interestingly, these two mutations at the same amino acid position cause E1 (and hence PDC) deficiency by apparently different mechanisms. Recombinant human R234Q E1 had similar V(max) (25.7 +/- 4.4 units/mg E1) and apparent K(m) (101 +/- 4 nM) values for TPP as recombinant wild-type human E1, while R234G E1 had no significant change in V(max) (33.6 +/- 4.7 units/mg E1) but had a 7-fold increase in its apparent K(m) value for TPP (497 +/- 25 nM). Both of the R234 mutant proteins had similar apparent K(m) values for pyruvate. Both R234Q and R234G mutant proteins displayed similar phosphorylation rates of sites 1 and 2 by pyruvate dehydrogenase kinase 2 (PDK2) and site 3 by PDK1 compared to wild-type E1. Phosphorylated R234Q E1, R234G E1, and wild-type E1 also had similar dephosphorylation rates of sites 1 and 2 by phosphopyruvate dehydrogenase phosphatase 1. The rate of dephosphorylation of site 3 was about 50% for R234Q E1 and without a significant change for R234G E1 compared to the wild type. The data indicate that the patients with the R234G E1 mutation are symptomatic due to a decreased ability of this mutant protein to bind TPP, whereas the patients with the R234Q E1 mutation are symptomatic due to a decreased rate of dephosphorylation of site 3, hence keeping the enzyme in a phosphorylated/inactivated form.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0003-9861
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
395
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
121-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11673873-Amino Acid Substitution, pubmed-meshheading:11673873-Arginine, pubmed-meshheading:11673873-Binding Sites, pubmed-meshheading:11673873-Enzyme Activation, pubmed-meshheading:11673873-Enzyme Stability, pubmed-meshheading:11673873-Humans, pubmed-meshheading:11673873-Isoenzymes, pubmed-meshheading:11673873-Mutagenesis, Site-Directed, pubmed-meshheading:11673873-Phosphoric Monoester Hydrolases, pubmed-meshheading:11673873-Phosphorylation, pubmed-meshheading:11673873-Protein Kinases, pubmed-meshheading:11673873-Protein Subunits, pubmed-meshheading:11673873-Protein-Serine-Threonine Kinases, pubmed-meshheading:11673873-Pyruvate Dehydrogenase (Lipoamide), pubmed-meshheading:11673873-Pyruvate Dehydrogenase Complex Deficiency Disease, pubmed-meshheading:11673873-Temperature
pubmed:year
2001
pubmed:articleTitle
Differential effects of two mutations at arginine-234 in the alpha subunit of human pyruvate dehydrogenase.
pubmed:affiliation
Department of Biochemistry, State University of New York at Buffalo, Buffalo, New York 14214, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.