The synthesis of ATP by glycolytic enzymes in the postsynaptic density and the effect of endogenously generated nitric oxide.
The major contribution of this paper is the finding of a glycolytic source of ATP in the isolated postsynaptic density (PSD). The enzymes involved in the generation of ATP are glyceraldehyde-3-phosphate dehydrogenase (G3PD) and phosphoglycerate kinase (PGK). Lactate dehydrogenase (LDH) is available for the regeneration of NAD+, as well as aldolase for the regeneration of glyceraldehyde-3-phosphate (G3P). The ATP was shown to be used by the PSD Ca2+/calmodulin-dependent protein kinase and can probably be used by two other PSD kinases, protein kinase A and protein kinase C. We confirmed by immunocytochemistry the presence of G3PD in the PSD and its binding to actin. Also present in the PSD is NO synthase, the source of NO. NO increases the binding of NAD, a G3PD cofactor, to G3PD and inhibits its activity as also found by others. The increased NAD binding resulted in an increase in G3PD binding to actin. We confirmed the autophosphorylation of G3PD by ATP, and further found that this procedure also increased the binding of G3PD to actin. ATP and NO are connected in that the formation of NO from NOS at the PSD resulted, in the presence of NAD, in a decrease of ATP formation in the PSD. In the discussion, we raise the possible roles of G3PD and of ATP in protein synthesis at the PSD, the regulation by NO, as well as the overall regulatory role of the PSD complex in synaptic transmission.
Wu
K
K
Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway 08854, USA.
Aoki
C
C
Elste
A
A
Rogalski-Wilk
A A
AA
Siekevitz
P
P
D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D002384:Catalysis; D002540:Cerebral Cortex / Q000201:enzymology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D006019:Glycolysis; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D010735:Phosphoglycerate Kinase / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D013552:Swine; D013569:Synapses / Q000201:enzymology*
D000199:Actins; D009243:NAD; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010735:Phosphoglycerate Kinase