5573.doi:10.1186/1742-2094-10-134 Cite this article as: Ou-Yang and Van Nostrand: The absence of myelin basic protein promotes neuroinflammation and reduces amyloid -protein accumulation in Tg-5xFAD mice. Journal of Neuroinflammation 2013 10:134.Submit your next manuscript to BioMed Central and take full advantage of:Convenient online submission Thorough peer review No space constraints or color figure charges Immediate publication on acceptance Inclusion in PubMed, CAS, Scopus and Google Scholar Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral/submit
Over the last years a large body of evidence has shown that glycolytic enzymes in a variety of cells may form metabolically active macromolecular complexes [1, for a review see: 2,3], whose stability is regulated directly and indirectly by calcium ions [4,5] and glycolytic intermediates [6,7]. Such association not only alters the regulatory properties and the kinetics of glycolytic enzymes [8], but may also facilitate the channeling of substrates between metabolically sequential enzymes increasing the velocity of the glycolytic pathway [9, for a review see: 2,3]. For years it was a common belief that lactate produced in glycolysis in a contracting muscle is transported via the blood stream to the liver where it is converted to glucose, which is subsequently transported back to the muscle (“the Cori cycle”). However, evidence has accumulated that in skeletal muscle up to 50 of lactate is converted to glycogen [10]. This suggests that glyconeogenesis, glycogen synthesis from non-carbohydrates, significantly contributes to the maintenance of energy stores in vertebrate striated muscle.Frexalimab Additionally, it has been demonstrated that the glyconeogenic enzymes also form protein complexes that may enable substrate channeling [11].Cediranib Fructose 1,6-bisphosphatase (FBPase; EC 3.PMID:24367939 1.3.11) is a key enzyme of gluco- and glyconeogenesis. It catalyzes the hydrolysis of fructose 1,6-bisphosphate (F1,6P2) to fructose 6-phosphate (F6P) and inorganic phosphate, in the presence of divalent metal ions such as Mg2+, Mn2+, Co2+ or Zn2+ [12,13]. The enzyme is activated by several monovalent cations (e.g. K+, NH4+, Tl+) [14], inhibited competitively by fructose 2,6-bisphosphate (F2,6P2) andPLOS ONE | www.plosone.orgallosterically by adenosine 59-monophosphate (AMP) and nicotinamide adenine dinucleotide (NAD) [12,15]. FBPase is also inhibited in an unknown manner by Ca2+ [16]. Vertebrate genomes contain two distinct genes FBP1 and FBP2, coding two FBPase isozymes. A protein product of the FBP1 gene liver FBPase, is expressed mainly in gluconeogenic organs, where it functions as a regulator of glucose synthesis from non-carbohydrates. The muscle FBPase isozyme is the sole FBPase isozyme in striated muscle and it is widely expressed in nongluconeogenic cells [17]. Mammalian muscle FBPase in comparison to the liver isozyme, is about 100 times more susceptible to the action of the allosteric inhibitors AMP and NAD, and about 1,000 times more sensitive to inhibition by Ca2+ [11,13,15,16] the most potent activator of glycolysis in striated muscle. Moreover, calcium not only inhibits muscle FBPase but also disrupts the Z-line based FBPase ldolase complex in striated muscles, blocking the re-synthesis of glycogen during high-intensity exercise [18,19]. However, a mechanism of this action by Ca2+ is unclear. Mammalian FBPase is a homotetramer [20] and exists in at least two conforma.